problem
stringlengths 16
191
| explanation
stringlengths 6
29k
⌀ | type
stringlengths 3
136
⌀ |
|---|---|---|
What is (are) Stickler syndrome ? | Stickler syndrome is a group of hereditary conditions characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and joint problems. These signs and symptoms vary widely among affected individuals. A characteristic feature of Stickler syndrome is a somewhat flattened facial appearance. This appearance results from underdeveloped bones in the middle of the face, including the cheekbones and the bridge of the nose. A particular group of physical features called Pierre Robin sequence is also common in people with Stickler syndrome. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a tongue that is placed further back than normal (glossoptosis), and a small lower jaw (micrognathia). This combination of features can lead to feeding problems and difficulty breathing. Many people with Stickler syndrome have severe nearsightedness (high myopia). In some cases, the clear gel that fills the eyeball (the vitreous) has an abnormal appearance, which is noticeable during an eye examination. Other eye problems are also common, including increased pressure within the eye (glaucoma), clouding of the lens of the eyes (cataracts), and tearing of the lining of the eye (retinal detachment). These eye abnormalities cause impaired vision or blindness in some cases. In people with Stickler syndrome, hearing loss varies in degree and may become more severe over time. The hearing loss may be sensorineural, meaning that it results from changes in the inner ear, or conductive, meaning that it is caused by abnormalities of the middle ear. Most people with Stickler syndrome have skeletal abnormalities that affect the joints. The joints of affected children and young adults may be loose and very flexible (hypermobile), though joints become less flexible with age. Arthritis often appears early in life and may cause joint pain or stiffness. Problems with the bones of the spine (vertebrae) can also occur, including abnormal curvature of the spine (scoliosis or kyphosis) and flattened vertebrae (platyspondyly). These spinal abnormalities may cause back pain. Researchers have described several types of Stickler syndrome, which are distinguished by their genetic causes and their patterns of signs and symptoms. In particular, the eye abnormalities and severity of hearing loss differ among the types. Type I has the highest risk of retinal detachment. Type II also includes eye abnormalities, but type III does not (and is often called non-ocular Stickler syndrome). Types II and III are more likely than type I to have significant hearing loss. Types IV, V, and VI are very rare and have each been diagnosed in only a few individuals. A condition similar to Stickler syndrome, called Marshall syndrome, is characterized by a distinctive facial appearance, eye abnormalities, hearing loss, and early-onset arthritis. Marshall syndrome can also include short stature. Some researchers have classified Marshall syndrome as a variant of Stickler syndrome, while others consider it to be a separate disorder. | Stickler syndrome |
How many people are affected by Stickler syndrome ? | Stickler syndrome affects an estimated 1 in 7,500 to 9,000 newborns. Type I is the most common form of the condition. | Stickler syndrome |
What are the genetic changes related to Stickler syndrome ? | Mutations in several genes cause the different types of Stickler syndrome. Between 80 and 90 percent of all cases are classified as type I and are caused by mutations in the COL2A1 gene. Another 10 to 20 percent of cases are classified as type II and result from mutations in the COL11A1 gene. Marshall syndrome, which may be a variant of Stickler syndrome, is also caused by COL11A1 gene mutations. Stickler syndrome types III through VI result from mutations in other, related genes. All of the genes associated with Stickler syndrome provide instructions for making components of collagens, which are complex molecules that give structure and strength to the connective tissues that support the body's joints and organs. Mutations in any of these genes impair the production, processing, or assembly of collagen molecules. Defective collagen molecules or reduced amounts of collagen impair the development of connective tissues in many different parts of the body, leading to the varied features of Stickler syndrome. Not all individuals with Stickler syndrome have mutations in one of the known genes. Researchers believe that mutations in other genes may also cause this condition, but those genes have not been identified. | Stickler syndrome |
Is Stickler syndrome inherited ? | Stickler syndrome types I, II, and III are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits a gene mutation from one affected parent. Other cases result from new mutations. These cases occur in people with no history of Stickler syndrome in their family. Marshall syndrome also typically has an autosomal dominant pattern of inheritance. Stickler syndrome types IV, V, and VI are inherited in an autosomal recessive pattern. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | Stickler syndrome |
What are the treatments for Stickler syndrome ? | These resources address the diagnosis or management of Stickler syndrome: - Gene Review: Gene Review: Stickler Syndrome - Genetic Testing Registry: Marshall syndrome - Genetic Testing Registry: Stickler syndrome - MedlinePlus Encyclopedia: Pierre Robin Syndrome - Merck Manual Consumer Version: Detachment of the Retina - Stickler Involved People: Clinical Characteristics & Diagnostic Criteria - Stickler Involved People: Stickler Syndrome Recognition, Diagnosis, Treatment These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Stickler syndrome |
What is (are) Klippel-Feil syndrome ? | Klippel-Feil syndrome is a bone disorder characterized by the abnormal joining (fusion) of two or more spinal bones in the neck (cervical vertebrae). The vertebral fusion is present from birth. Three major features result from this vertebral fusion: a short neck, the resulting appearance of a low hairline at the back of the head, and a limited range of motion in the neck. Most affected people have one or two of these characteristic features. Less than half of all individuals with Klippel-Feil syndrome have all three classic features of this condition. In people with Klippel-Feil syndrome, the fused vertebrae can limit the range of movement of the neck and back as well as lead to chronic headaches and muscle pain in the neck and back that range in severity. People with minimal bone involvement often have fewer problems compared to individuals with several vertebrae affected. The shortened neck can cause a slight difference in the size and shape of the right and left sides of the face (facial asymmetry). Trauma to the spine, such as a fall or car accident, can aggravate problems in the fused area. Fusion of the vertebrae can lead to nerve damage in the head, neck, or back. Over time, individuals with Klippel-Feil syndrome can develop a narrowing of the spinal canal (spinal stenosis) in the neck, which can compress and damage the spinal cord. Rarely, spinal nerve abnormalities may cause abnormal sensations or involuntary movements in people with Klippel-Feil syndrome. Affected individuals may develop a painful joint disorder called osteoarthritis around the areas of fused bone or experience painful involuntary tensing of the neck muscles (cervical dystonia). In addition to the fused cervical bones, people with this condition may have abnormalities in other vertebrae. Many people with Klippel-Feil syndrome have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae; fusion of additional vertebrae below the neck may also occur. People with Klippel-Feil syndrome may have a wide variety of other features in addition to their spine abnormalities. Some people with this condition have hearing difficulties, eye abnormalities, an opening in the roof of the mouth (cleft palate), genitourinary problems such as abnormal kidneys or reproductive organs, heart abnormalities, or lung defects that can cause breathing problems. Affected individuals may have other skeletal defects including arms or legs of unequal length (limb length discrepancy), which can result in misalignment of the hips or knees. Additionally, the shoulder blades may be underdeveloped so that they sit abnormally high on the back, a condition called Sprengel deformity. Rarely, structural brain abnormalities or a type of birth defect that occurs during the development of the brain and spinal cord (neural tube defect) can occur in people with Klippel-Feil syndrome. In some cases, Klippel-Feil syndrome occurs as a feature of another disorder or syndrome, such as Wildervanck syndrome or hemifacial microsomia. In these instances, affected individuals have the signs and symptoms of both Klippel-Feil syndrome and the additional disorder. | Klippel-Feil syndrome |
How many people are affected by Klippel-Feil syndrome ? | Klippel-Feil syndrome is estimated to occur in 1 in 40,000 to 42,000 newborns worldwide. Females seem to be affected slightly more often than males. | Klippel-Feil syndrome |
What are the genetic changes related to Klippel-Feil syndrome ? | Mutations in the GDF6, GDF3, or MEOX1 gene can cause Klippel-Feil syndrome. These genes are involved in proper bone development. The protein produced from the GDF6 gene is necessary for the formation of bones and joints, including those in the spine. While the protein produced from the GDF3 gene is known to be involved in bone development, its exact role is unclear. The protein produced from the MEOX1 gene, called homeobox protein MOX-1, regulates the process that begins separating vertebrae from one another during early development. GDF6 and GDF3 gene mutations that cause Klippel-Feil syndrome likely lead to reduced function of the respective proteins. MEOX1 gene mutations lead to a complete lack of homeobox protein MOX-1. Although the GDF6, GDF3, and homeobox protein MOX-1 proteins are involved in bone development, particularly formation of vertebrae, it is unclear how a shortage of one of these proteins leads to incomplete separation of the cervical vertebrae in people with Klippel-Feil syndrome. When Klippel-Feil syndrome is a feature of another disorder, it is caused by mutations in genes involved in the other disorder. | Klippel-Feil syndrome |
Is Klippel-Feil syndrome inherited ? | When Klippel-Feil syndrome is caused by mutations in the GDF6 or GDF3 genes, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. When caused by mutations in the MEOX1 gene, Klippel-Feil syndrome is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. As a feature of another disorder, Klippel-Feil syndrome is inherited in whatever pattern the other disorder follows. | Klippel-Feil syndrome |
What are the treatments for Klippel-Feil syndrome ? | These resources address the diagnosis or management of Klippel-Feil syndrome: - Genetic Testing Registry: Klippel Feil syndrome - Genetic Testing Registry: Klippel-Feil syndrome 1, autosomal dominant - Genetic Testing Registry: Klippel-Feil syndrome 2, autosomal recessive - Genetic Testing Registry: Klippel-Feil syndrome 3, autosomal dominant These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Klippel-Feil syndrome |
What is (are) 17 alpha-hydroxylase/17,20-lyase deficiency ? | 17 alpha()-hydroxylase/17,20-lyase deficiency is a condition that affects the function of certain hormone-producing glands called the gonads (ovaries in females and testes in males) and the adrenal glands. The gonads direct sexual development before birth and during puberty and are important for reproduction. The adrenal glands, which are located on top of the kidneys, regulate the production of certain hormones, including those that control salt levels in the body. People with 17-hydroxylase/17,20-lyase deficiency have an imbalance of many of the hormones that are made in these glands. 17-hydroxylase/17,20-lyase deficiency is one of a group of disorders, known as congenital adrenal hyperplasias, that impair hormone production and disrupt sexual development and maturation. Hormone imbalances lead to the characteristic signs and symptoms of 17-hydroxylase/17,20-lyase deficiency, which include high blood pressure (hypertension), low levels of potassium in the blood (hypokalemia), and abnormal sexual development. The severity of the features varies. Two forms of the condition are recognized: complete 17-hydroxylase/17,20-lyase deficiency, which is more severe, and partial 17-hydroxylase/17,20-lyase deficiency, which is typically less so. Males and females are affected by disruptions to sexual development differently. Females (who have two X chromosomes) with 17-hydroxylase/17,20-lyase deficiency are born with normal external female genitalia; however, the internal reproductive organs, including the uterus and ovaries, may be underdeveloped. Women with complete 17-hydroxylase/17,20-lyase deficiency do not develop secondary sex characteristics, such as breasts and pubic hair, and do not menstruate (amenorrhea). Women with partial 17-hydroxylase/17,20-lyase deficiency may develop some secondary sex characteristics; menstruation is typically irregular or absent. Either form of the disorder results in an inability to conceive a baby (infertility). In affected individuals who are chromosomally male (having an X and a Y chromosome), problems with sexual development lead to abnormalities of the external genitalia. The most severely affected are born with characteristically female external genitalia and are generally raised as females. However, because they do not have female internal reproductive organs, these individuals have amenorrhea and do not develop female secondary sex characteristics. These individuals have testes, but they are abnormally located in the abdomen (undescended). Sometimes, complete 17-hydroxylase/17,20-lyase deficiency leads to external genitalia that do not look clearly male or clearly female (ambiguous genitalia). Males with partial 17-hydroxylase/17,20-lyase deficiency usually have abnormal male genitalia, such as a small penis (micropenis), the opening of the urethra on the underside of the penis (hypospadias), or a scrotum divided into two lobes (bifid scrotum). Males with either complete or partial 17-hydroxylase/17,20-lyase deficiency are also infertile. | 17 alpha-hydroxylase/17,20-lyase deficiency |
How many people are affected by 17 alpha-hydroxylase/17,20-lyase deficiency ? | 17-hydroxylase/17,20-lyase deficiency accounts for about 1 percent of congenital adrenal hyperplasia cases. It is estimated to occur in 1 in 1 million people worldwide. | 17 alpha-hydroxylase/17,20-lyase deficiency |
What are the genetic changes related to 17 alpha-hydroxylase/17,20-lyase deficiency ? | 17-hydroxylase/17,20-lyase deficiency is caused by mutations in the CYP17A1 gene. The protein produced from this gene is involved in the formation of steroid hormones. This group of hormones includes sex hormones such as testosterone and estrogen, which are needed for normal sexual development and reproduction; mineralocorticoids, which help regulate the body's salt and water balance; and glucocorticoids, which are involved in maintaining blood sugar levels and regulating the body's response to stress. Steroid hormones are produced through a series of chemical reactions. The CYP17A1 enzyme performs two important reactions in this process. The enzyme has 17 alpha()-hydroxylase activity, which is important for production of glucocorticoids and sex hormones. CYP17A1 also has 17,20-lyase activity, which is integral to the production of sex hormones. 17-hydroxylase/17,20-lyase deficiency results from a shortage (deficiency) of both enzyme activities. The amount of remaining enzyme activity determines whether a person will have the complete or partial form of the disorder. Individuals with the complete form have CYP17A1 gene mutations that result in the production of an enzyme with very little or no 17-hydroxylase and 17,20-lyase activity. People with the partial form of this condition have CYP17A1 gene mutations that allow some enzyme activity, although at reduced levels. With little or no 17-hydroxylase activity, production of glucocorticoids is impaired, and instead, mineralocorticoids are produced. An excess of these salt-regulating hormones leads to hypertension and hypokalemia. Loss of 17,20-lyase activity impairs sex hormone production. Shortage of these hormones disrupts development of the reproductive system and impairs the onset of puberty in males and females with 17-hydroxylase/17,20-lyase deficiency. | 17 alpha-hydroxylase/17,20-lyase deficiency |
Is 17 alpha-hydroxylase/17,20-lyase deficiency inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | 17 alpha-hydroxylase/17,20-lyase deficiency |
What are the treatments for 17 alpha-hydroxylase/17,20-lyase deficiency ? | These resources address the diagnosis or management of 17 alpha-hydroxylase/17,20-lyase deficiency: - Genetic Testing Registry: Deficiency of steroid 17-alpha-monooxygenase These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | 17 alpha-hydroxylase/17,20-lyase deficiency |
What is (are) spastic paraplegia type 15 ? | Spastic paraplegia type 15 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Spastic paraplegia type 15 is classified as a complex hereditary spastic paraplegia because it involves all four limbs as well as additional features, including abnormalities of the brain. In addition to the muscles and brain, spastic paraplegia type 15 affects the peripheral nervous system, which consists of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Spastic paraplegia type 15 usually becomes apparent in childhood or adolescence with the development of weak muscle tone (hypotonia), difficulty walking, or intellectual disability. In almost all affected individuals, the tissue connecting the left and right halves of the brain (corpus callosum) is abnormally thin and becomes thinner over time. Additionally, there is often a loss (atrophy) of nerve cells in several parts of the brain, including the cerebral cortex, which controls thinking and emotions, and the cerebellum, which coordinates movement. People with this form of spastic paraplegia can have numbness, tingling, or pain in the arms and legs (sensory neuropathy); impairment of the nerves used for muscle movement (motor neuropathy); exaggerated reflexes (hyperreflexia) of the lower limbs; muscle wasting (amyotrophy); or reduced bladder control. Rarely, spastic paraplegia type 15 is associated with a group of movement abnormalities called parkinsonism, which includes tremors, rigidity, and unusually slow movement (bradykinesia). People with spastic paraplegia type 15 may have an eye condition called pigmentary maculopathy that often impairs vision. This condition results from the breakdown (degeneration) of tissue at the back of the eye called the macula, which is responsible for sharp central vision. Most people with spastic paraplegia type 15 experience a decline in intellectual ability and an increase in muscle weakness and nerve abnormalities over time. As the condition progresses, many people require walking aids or wheelchair assistance in adulthood. | spastic paraplegia type 15 |
How many people are affected by spastic paraplegia type 15 ? | Spastic paraplegia type 15 is a rare condition, although its exact prevalence is unknown. | spastic paraplegia type 15 |
What are the genetic changes related to spastic paraplegia type 15 ? | Mutations in the ZFYVE26 gene cause spastic paraplegia type 15. This gene provides instructions for making a protein called spastizin. This protein is important in a process called autophagy, in which worn-out cell parts and unneeded proteins are recycled within cells. Specifically, spastizin is involved in the formation and maturation of sacs called autophagosomes (or autophagic vacuoles) that transport unneeded materials to be broken down. Spastizin also plays a role in the process by which dividing cells separate from one another (cytokinesis). Many ZFYVE26 gene mutations that cause spastic paraplegia type 15 result in a shortened spastizin protein that is quickly broken down. As a result, functional autophagosomes are not produced, autophagy cannot occur, and recycling of materials within cells is decreased. An inability to break down unneeded materials, and the subsequent accumulation of these materials in cells, leads to cell dysfunction and often cell death. The loss of cells in the brain and other parts of the body is responsible for many of the features of spastic paraplegia type 15. It is unclear whether a lack of spastizin protein interferes with normal cytokinesis and whether impaired cell division contributes to the signs and symptoms of spastic paraplegia type 15. | spastic paraplegia type 15 |
Is spastic paraplegia type 15 inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | spastic paraplegia type 15 |
What are the treatments for spastic paraplegia type 15 ? | These resources address the diagnosis or management of spastic paraplegia type 15: - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview - Spastic Paraplegia Foundation, Inc: Treatments and Therapies These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | spastic paraplegia type 15 |
What is (are) Char syndrome ? | Char syndrome is a condition that affects the development of the face, heart, and limbs. It is characterized by a combination of three major features: a distinctive facial appearance, a heart defect called patent ductus arteriosus, and hand abnormalities. Most people with Char syndrome have a characteristic facial appearance that includes flattened cheek bones and a flat nasal bridge (the area of the nose between the eyes). The tip of the nose is also flat and broad. The eyes are wide-set with droopy eyelids (ptosis) and outside corners that point downward (down-slanting palpebral fissures). Additional facial differences include a shortened distance between the nose and upper lip (a short philtrum), a triangular-shaped mouth, and thick, prominent lips. Patent ductus arteriosus is a common heart defect in newborns, and it occurs in most babies with Char syndrome. Before birth, the ductus arteriosus forms a connection between two major arteries (the aorta and the pulmonary artery). This connection normally closes shortly after birth, but it remains open in babies with patent ductus arteriosus. If untreated, this heart defect causes infants to breathe rapidly, feed poorly, and gain weight slowly. In severe cases, it can lead to heart failure. People with patent ductus arteriosus also have an increased risk of infection. Hand abnormalities are another feature of Char syndrome. In most people with this condition, the middle section of the fifth (pinky) finger is shortened or absent. Other abnormalities of the hands and feet have been reported but are less common. | Char syndrome |
How many people are affected by Char syndrome ? | Char syndrome is rare, although its exact incidence is unknown. Only a few families with this condition have been identified worldwide. | Char syndrome |
What are the genetic changes related to Char syndrome ? | Mutations in the TFAP2B gene cause Char syndrome. This gene provides instructions for making a protein known as transcription factor AP-2. A transcription factor is a protein that attaches (binds) to specific regions of DNA and helps control the activity of particular genes. Transcription factor AP-2 regulates genes that are involved in development before birth. In particular, this protein appears to play a role in the normal formation of structures in the face, heart, and limbs. TFAP2B mutations alter the structure of transcription factor AP-2. Some of these mutations prevent the protein from binding to DNA, while other mutations render it unable to regulate the activity of other genes. A loss of this protein's function disrupts the normal development of several parts of the body before birth, resulting in the major features of Char syndrome. | Char syndrome |
Is Char syndrome inherited ? | This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases may result from new mutations in the gene and occur in people with no history of the disorder in their family. | Char syndrome |
What are the treatments for Char syndrome ? | These resources address the diagnosis or management of Char syndrome: - Gene Review: Gene Review: Char Syndrome - Genetic Testing Registry: Char syndrome - MedlinePlus Encyclopedia: Patent Ductus Arteriosus These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Char syndrome |
What is (are) nonsyndromic holoprosencephaly ? | Nonsyndromic holoprosencephaly is an abnormality of brain development that also affects the head and face. Normally, the brain divides into two halves (hemispheres) during early development. Holoprosencephaly occurs when the brain fails to divide properly into the right and left hemispheres. This condition is called nonsyndromic to distinguish it from other types of holoprosencephaly caused by genetic syndromes, chromosome abnormalities, or substances that cause birth defects (teratogens). The severity of nonsyndromic holoprosencephaly varies widely among affected individuals, even within the same family. Nonsyndromic holoprosencephaly can be grouped into four types according to the degree of brain division. From most to least severe, the types are known as alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In the most severe forms of nonsyndromic holoprosencephaly, the brain does not divide at all. These affected individuals have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. Most babies with severe nonsyndromic holoprosencephaly die before birth or soon after. In the less severe forms, the brain is partially divided and the eyes are usually set close together (hypotelorism). The life expectancy of these affected individuals varies depending on the severity of symptoms. People with nonsyndromic holoprosencephaly often have a small head (microcephaly), although they can develop a buildup of fluid in the brain (hydrocephalus) that causes increased head size (macrocephaly). Other features may include an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip), one central front tooth instead of two (a single maxillary central incisor), and a flat nasal bridge. The eyeballs may be abnormally small (microphthalmia) or absent (anophthalmia). Some individuals with nonsyndromic holoprosencephaly have a distinctive pattern of facial features, including a narrowing of the head at the temples, outside corners of the eyes that point upward (upslanting palpebral fissures), large ears, a short nose with upturned nostrils, and a broad and deep space between the nose and mouth (philtrum). In general, the severity of facial features is directly related to the severity of the brain abnormalities. However, individuals with mildly affected facial features can have severe brain abnormalities. Some people do not have apparent structural brain abnormalities but have some of the facial features associated with this condition. These individuals are considered to have a form of the disorder known as microform holoprosencephaly and are typically identified after the birth of a severely affected family member. Most people with nonsyndromic holoprosencephaly have developmental delay and intellectual disability. Affected individuals also frequently have a malfunctioning pituitary gland, which is a gland located at the base of the brain that produces several hormones. Because pituitary dysfunction leads to the partial or complete absence of these hormones, it can cause a variety of disorders. Most commonly, people with nonsyndromic holoprosencephaly and pituitary dysfunction develop diabetes insipidus, a condition that disrupts the balance between fluid intake and urine excretion. Dysfunction in other parts of the brain can cause seizures, feeding difficulties, and problems regulating body temperature, heart rate, and breathing. The sense of smell may be diminished (hyposmia) or completely absent (anosmia) if the part of the brain that processes smells is underdeveloped or missing. | nonsyndromic holoprosencephaly |
How many people are affected by nonsyndromic holoprosencephaly ? | Nonsyndromic holoprosencephaly accounts for approximately 25 to 50 percent of all cases of holoprosencephaly, which affects an estimated 1 in 10,000 newborns. | nonsyndromic holoprosencephaly |
What are the genetic changes related to nonsyndromic holoprosencephaly ? | Mutations in 11 genes have been found to cause nonsyndromic holoprosencephaly. These genes provide instructions for making proteins that are important for normal embryonic development, particularly for determining the shape of the brain and face. About 25 percent of people with nonsyndromic holoprosencephaly have a mutation in one of these four genes: SHH, ZIC2, SIX3, or TGIF1. Mutations in the other genes related to nonsyndromic holoprosencephaly are found in only a small percentage of cases. Many individuals with this condition do not have an identified gene mutation. The cause of the disorder is unknown in these individuals. The brain normally divides into right and left hemispheres during the third to fourth week of pregnancy. To establish the line that separates the two hemispheres (the midline), the activity of many genes must be tightly regulated and coordinated. These genes provide instructions for making signaling proteins, which instruct the cells within the brain to form the right and left hemispheres. Signaling proteins are also important for the formation of the eyes. During early development, the cells that develop into the eyes form a single structure called the eye field. This structure is located in the center of the developing face. The signaling protein produced from the SHH gene causes the eye field to separate into two distinct eyes. The SIX3 gene is involved in the formation of the lens of the eye and the specialized tissue at the back of the eye that detects light and color (the retina). Mutations in the genes that cause nonsyndromic holoprosencephaly lead to the production of abnormal or nonfunctional signaling proteins. Without the correct signals, the eyes will not form normally and the brain does not separate into two hemispheres. The development of other parts of the face is affected if the eyes do not move to their proper position. The signs and symptoms of nonsyndromic holoprosencephaly are caused by abnormal development of the brain and face. Researchers believe that other genetic or environmental factors, many of which have not been identified, play a role in determining the severity of nonsyndromic holoprosencephaly. | nonsyndromic holoprosencephaly |
Is nonsyndromic holoprosencephaly inherited ? | Nonsyndromic holoprosencephaly is inherited in an autosomal dominant pattern, which means an alteration in one copy of a gene in each cell is usually sufficient to cause the disorder. However, not all people with a gene mutation will develop signs and symptoms of the condition. In some cases, an affected person inherits the mutation from one parent who may or may not have mild features of the condition. Other cases result from a new gene mutation and occur in people with no history of the disorder in their family. | nonsyndromic holoprosencephaly |
What are the treatments for nonsyndromic holoprosencephaly ? | These resources address the diagnosis or management of nonsyndromic holoprosencephaly: - Gene Review: Gene Review: Holoprosencephaly Overview - Genetic Testing Registry: Holoprosencephaly 1 - Genetic Testing Registry: Holoprosencephaly 10 - Genetic Testing Registry: Holoprosencephaly 2 - Genetic Testing Registry: Holoprosencephaly 3 - Genetic Testing Registry: Holoprosencephaly 4 - Genetic Testing Registry: Holoprosencephaly 5 - Genetic Testing Registry: Holoprosencephaly 6 - Genetic Testing Registry: Holoprosencephaly 7 - Genetic Testing Registry: Holoprosencephaly 8 - Genetic Testing Registry: Holoprosencephaly 9 - Genetic Testing Registry: Holoprosencephaly sequence - Genetic Testing Registry: NODAL-Related Holoprosencephaly These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | nonsyndromic holoprosencephaly |
What is (are) lactate dehydrogenase deficiency ? | Lactate dehydrogenase deficiency is a condition that affects how the body breaks down sugar to use as energy in cells, primarily muscle cells. There are two types of this condition: lactate dehydrogenase-A deficiency (sometimes called glycogen storage disease XI) and lactate dehydrogenase-B deficiency. People with lactate dehydrogenase-A deficiency experience fatigue, muscle pain, and cramps during exercise (exercise intolerance). In some people with lactate dehydrogenase-A deficiency, high-intensity exercise or other strenuous activity leads to the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure. Some people with lactate dehydrogenase-A deficiency develop skin rashes. The severity of the signs and symptoms among individuals with lactate dehydrogenase-A deficiency varies greatly. People with lactate dehydrogenase-B deficiency typically do not have any signs or symptoms of the condition. They do not have difficulty with physical activity or any specific physical features related to the condition. Affected individuals are usually discovered only when routine blood tests reveal reduced lactate dehydrogenase activity. | lactate dehydrogenase deficiency |
How many people are affected by lactate dehydrogenase deficiency ? | Lactate dehydrogenase deficiency is a rare disorder. In Japan, this condition affects 1 in 1 million individuals; the prevalence of lactate dehydrogenase deficiency in other countries is unknown. | lactate dehydrogenase deficiency |
What are the genetic changes related to lactate dehydrogenase deficiency ? | Mutations in the LDHA gene cause lactate dehydrogenase-A deficiency, and mutations in the LDHB gene cause lactate dehydrogenase-B deficiency. These genes provide instructions for making the lactate dehydrogenase-A and lactate dehydrogenase-B pieces (subunits) of the lactate dehydrogenase enzyme. This enzyme is found throughout the body and is important for creating energy for cells. There are five different forms of this enzyme, each made up of four protein subunits. Various combinations of the lactate dehydrogenase-A and lactate dehydrogenase-B subunits make up the different forms of the enzyme. The version of lactate dehydrogenase made of four lactate dehydrogenase-A subunits is found primarily in skeletal muscles, which are muscles used for movement. Skeletal muscles need large amounts of energy during high-intensity physical activity when the body's oxygen intake is not sufficient for the amount of energy required (anaerobic exercise). During anaerobic exercise, the lactate dehydrogenase enzyme is involved in the breakdown of sugar stored in the muscles (in the form of glycogen) to create additional energy. During the final stage of glycogen breakdown, lactate dehydrogenase converts a molecule called pyruvate to a similar molecule called lactate. Mutations in the LDHA gene result in the production of an abnormal lactate dehydrogenase-A subunit that cannot attach (bind) to other subunits to form the lactate dehydrogenase enzyme. A lack of functional subunit reduces the amount of enzyme that is formed, mostly affecting skeletal muscles. As a result, glycogen is not broken down efficiently, leading to decreased energy in muscle cells. When muscle cells do not get sufficient energy during exercise or strenuous activity, the muscles become weak and muscle tissue can break down, as experienced by people with lactate dehydrogenase-A deficiency. The version of lactate dehydrogenase made of four lactate dehydrogenase-B subunits is found primarily in heart (cardiac) muscle. In cardiac muscle, lactate dehydrogenase converts lactate to pyruvate, which can participate in other chemical reactions to create energy. LDHB gene mutations lead to the production of an abnormal lactate dehydrogenase-B subunit that cannot form the lactate dehydrogenase enzyme. Even though lactate dehydrogenase activity is decreased in the cardiac muscle of people with lactate dehydrogenase-B deficiency, they do not appear to have any signs or symptoms related to their condition. It is unclear why this type of enzyme deficiency does not cause any health problems. | lactate dehydrogenase deficiency |
Is lactate dehydrogenase deficiency inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | lactate dehydrogenase deficiency |
What are the treatments for lactate dehydrogenase deficiency ? | These resources address the diagnosis or management of lactate dehydrogenase deficiency: - Genetic Testing Registry: Glycogen storage disease XI - Genetic Testing Registry: Lactate dehydrogenase B deficiency - MedlinePlus Encyclopedia: LDH Isoenzymes - MedlinePlus Encyclopedia: Lactate Dehydrogenase Test These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | lactate dehydrogenase deficiency |
What is (are) Diamond-Blackfan anemia ? | Diamond-Blackfan anemia is a disorder of the bone marrow. The major function of bone marrow is to produce new blood cells. In Diamond-Blackfan anemia, the bone marrow malfunctions and fails to make enough red blood cells, which carry oxygen to the body's tissues. The resulting shortage of red blood cells (anemia) usually becomes apparent during the first year of life. Symptoms of anemia include fatigue, weakness, and an abnormally pale appearance (pallor). People with Diamond-Blackfan anemia have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS), which is a disorder in which immature blood cells fail to develop normally. Affected individuals also have an increased risk of developing certain cancers, including a cancer of blood-forming tissue known as acute myeloid leukemia (AML) and a type of bone cancer called osteosarcoma. Approximately half of individuals with Diamond-Blackfan anemia have physical abnormalities. They may have an unusually small head size (microcephaly) and a low frontal hairline, along with distinctive facial features such as wide-set eyes (hypertelorism); droopy eyelids (ptosis); a broad, flat bridge of the nose; small, low-set ears; and a small lower jaw (micrognathia). Affected individuals may also have an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). They may have a short, webbed neck; shoulder blades which are smaller and higher than usual; and abnormalities of their hands, most commonly malformed or absent thumbs. About one-third of affected individuals have slow growth leading to short stature. Other features of Diamond-Blackfan anemia may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), or eyes that do not look in the same direction (strabismus). Affected individuals may also have kidney abnormalities; structural defects of the heart; and, in males, the opening of the urethra on the underside of the penis (hypospadias). The severity of Diamond-Blackfan anemia may vary, even within the same family. Increasingly, individuals with "non-classical" Diamond-Blackfan anemia have been identified. This form of the disorder typically has less severe symptoms that may include mild anemia beginning in adulthood. | Diamond-Blackfan anemia |
How many people are affected by Diamond-Blackfan anemia ? | Diamond-Blackfan anemia affects approximately 5 to 7 per million liveborn infants worldwide. | Diamond-Blackfan anemia |
What are the genetic changes related to Diamond-Blackfan anemia ? | Diamond-Blackfan anemia can be caused by mutations in the RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 genes. These genes provide instructions for making several of the approximately 80 different ribosomal proteins, which are components of cellular structures called ribosomes. Ribosomes process the cell's genetic instructions to create proteins. Each ribosome is made up of two parts (subunits) called the large and small subunits. The RPL5, RPL11, and RPL35A genes provide instructions for making ribosomal proteins that are among those found in the large subunit. The ribosomal proteins produced from the RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26 genes are among those found in the small subunit. The specific functions of each ribosomal protein within these subunits are unclear. Some ribosomal proteins are involved in the assembly or stability of ribosomes. Others help carry out the ribosome's main function of building new proteins. Studies suggest that some ribosomal proteins may have other functions, such as participating in chemical signaling pathways within the cell, regulating cell division, and controlling the self-destruction of cells (apoptosis). Mutations in any of the genes listed above are believed to affect the stability or function of the ribosomal proteins. Studies indicate that a shortage of functioning ribosomal proteins may increase the self-destruction of blood-forming cells in the bone marrow, resulting in anemia. Abnormal regulation of cell division or inappropriate triggering of apoptosis may contribute to the other health problems that affect some people with Diamond-Blackfan anemia. Approximately 25 percent of individuals with Diamond-Blackfan anemia have identified mutations in the RPS19 gene. About another 25 to 35 percent of individuals with this disorder have identified mutations in the RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, or RPS26 genes. In the remaining 40 to 50 percent of cases, the cause of the condition is unknown. Researchers suspect that other genes may also be associated with Diamond-Blackfan anemia. | Diamond-Blackfan anemia |
Is Diamond-Blackfan anemia inherited ? | This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In approximately 45 percent of cases, an affected person inherits the mutation from one affected parent. The remaining cases result from new mutations in the gene and occur in people with no history of the disorder in their family. | Diamond-Blackfan anemia |
What are the treatments for Diamond-Blackfan anemia ? | These resources address the diagnosis or management of Diamond-Blackfan anemia: - Gene Review: Gene Review: Diamond-Blackfan Anemia - Genetic Testing Registry: Aase syndrome - Genetic Testing Registry: Diamond-Blackfan anemia - Genetic Testing Registry: Diamond-Blackfan anemia 10 - Genetic Testing Registry: Diamond-Blackfan anemia 2 - Genetic Testing Registry: Diamond-Blackfan anemia 3 - Genetic Testing Registry: Diamond-Blackfan anemia 4 - Genetic Testing Registry: Diamond-Blackfan anemia 5 - Genetic Testing Registry: Diamond-Blackfan anemia 7 - Genetic Testing Registry: Diamond-Blackfan anemia 8 - Genetic Testing Registry: Diamond-Blackfan anemia 9 These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Diamond-Blackfan anemia |
What is (are) Kawasaki disease ? | Kawasaki disease is a sudden and time-limited (acute) illness that affects infants and young children. Affected children develop a prolonged fever lasting several days, a skin rash, and swollen lymph nodes in the neck (cervical lymphadenopathy). They also develop redness in the whites of the eyes (conjunctivitis) and redness (erythema) of the lips, lining of the mouth (oral mucosa), tongue, palms of the hands, and soles of the feet. Without treatment, 15 to 25 percent of individuals with Kawasaki disease develop bulging and thinning of the walls of the arteries that supply blood to the heart muscle (coronary artery aneurysms) or other damage to the coronary arteries, which can be life-threatening. | Kawasaki disease |
How many people are affected by Kawasaki disease ? | In the United States and other Western countries, Kawasaki disease occurs in approximately 1 in 10,000 children under 5 each year. The condition is 10 to 20 times more common in East Asia, including Japan, Korea, and Taiwan. | Kawasaki disease |
What are the genetic changes related to Kawasaki disease ? | The causes of Kawasaki disease are not well understood. The disorder is generally regarded as being the result of an abnormal immune system activation, but the triggers of this abnormal response are unknown. Because cases of the disorder tend to cluster geographically and by season, researchers have suggested that an infection may be involved. However, no infectious agent (such as a virus or bacteria) has been identified. A variation in the ITPKC gene has been associated with an increased risk of Kawasaki disease. The ITPKC gene provides instructions for making an enzyme called inositol 1,4,5-trisphosphate 3-kinase C. This enzyme helps limit the activity of immune system cells called T cells. T cells identify foreign substances and defend the body against infection. Reducing the activity of T cells when appropriate prevents the overproduction of immune proteins called cytokines that lead to inflammation and which, in excess, cause tissue damage. Researchers suggest that the ITPKC gene variation may interfere with the body's ability to reduce T cell activity, leading to inflammation that damages blood vessels and results in the signs and symptoms of Kawasaki disease. It appears likely that other factors, including changes in other genes, also influence the development of this complex disorder. | Kawasaki disease |
Is Kawasaki disease inherited ? | A predisposition to Kawasaki disease appears to be passed through generations in families, but the inheritance pattern is unknown. Children of parents who have had Kawasaki disease have twice the risk of developing the disorder compared to the general population. Children with affected siblings have a tenfold higher risk. | Kawasaki disease |
What are the treatments for Kawasaki disease ? | These resources address the diagnosis or management of Kawasaki disease: - Cincinnati Children's Hospital Medical Center - Genetic Testing Registry: Acute febrile mucocutaneous lymph node syndrome - National Heart, Lung, and Blood Institute: How is Kawasaki Disease Treated? These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Kawasaki disease |
What is (are) autosomal dominant hypocalcemia ? | Autosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals can have an imbalance of other molecules in the blood as well, including too much phosphate (hyperphosphatemia) or too little magnesium (hypomagnesemia). Some people with autosomal dominant hypocalcemia also have low levels of a hormone called parathyroid hormone (hypoparathyroidism). This hormone is involved in the regulation of calcium levels in the blood. Abnormal levels of calcium and other molecules in the body can lead to a variety of signs and symptoms, although about half of affected individuals have no associated health problems. The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, prickling or tingling sensations (paresthesias), or twitching of the nerves and muscles (neuromuscular irritability) in various parts of the body. More severely affected individuals develop seizures, usually in infancy or childhood. Sometimes, these symptoms occur only during episodes of illness or fever. Some people with autosomal dominant hypocalcemia have high levels of calcium in their urine (hypercalciuria), which can lead to deposits of calcium in the kidneys (nephrocalcinosis) or the formation of kidney stones (nephrolithiasis). These conditions can damage the kidneys and impair their function. Sometimes, abnormal deposits of calcium form in the brain, typically in structures called basal ganglia, which help control movement. A small percentage of severely affected individuals have features of a kidney disorder called Bartter syndrome in addition to hypocalcemia. These features can include a shortage of potassium (hypokalemia) and magnesium and a buildup of the hormone aldosterone (hyperaldosteronism) in the blood. The abnormal balance of molecules can raise the pH of the blood, which is known as metabolic alkalosis. The combination of features of these two conditions is sometimes referred to as autosomal dominant hypocalcemia with Bartter syndrome or Bartter syndrome type V. There are two types of autosomal dominant hypocalcemia distinguished by their genetic cause. The signs and symptoms of the two types are generally the same. | autosomal dominant hypocalcemia |
How many people are affected by autosomal dominant hypocalcemia ? | The prevalence of autosomal dominant hypocalcemia is unknown. The condition is likely underdiagnosed because it often causes no signs or symptoms. | autosomal dominant hypocalcemia |
What are the genetic changes related to autosomal dominant hypocalcemia ? | Autosomal dominant hypocalcemia is primarily caused by mutations in the CASR gene; these cases are known as type 1. A small percentage of cases, known as type 2, are caused by mutations in the GNA11 gene. The proteins produced from these genes work together to regulate the amount of calcium in the blood. The CASR gene provides instructions for making a protein called the calcium-sensing receptor (CaSR). Calcium molecules attach (bind) to the CaSR protein, which allows this protein to monitor and regulate the amount of calcium in the blood. G11, which is produced from the GNA11 gene, is one component of a signaling protein that works in conjunction with CaSR. When a certain concentration of calcium is reached, CaSR stimulates G11 to send signals to block processes that increase the amount of calcium in the blood. Mutations in the CASR or GNA11 gene lead to overactivity of the respective protein. The altered CaSR protein is more sensitive to calcium, meaning even low levels of calcium can trigger it to stimulate G11 signaling. Similarly, the altered G11 protein continues to send signals to prevent calcium increases, even when levels in the blood are very low. As a result, calcium levels in the blood remain low, causing hypocalcemia. Calcium plays an important role in the control of muscle movement, and a shortage of this molecule can lead to cramping or twitching of the muscles. Impairment of the processes that increase calcium can also disrupt the normal regulation of other molecules, such as phosphate and magnesium, leading to other signs of autosomal dominant hypocalcemia. Studies show that the lower the amount of calcium in the blood, the more severe the symptoms of the condition are. | autosomal dominant hypocalcemia |
Is autosomal dominant hypocalcemia inherited ? | This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the mutation from one affected parent. A small number of cases result from new mutations in the gene and occur in people with no history of the disorder in their family. | autosomal dominant hypocalcemia |
What are the treatments for autosomal dominant hypocalcemia ? | These resources address the diagnosis or management of autosomal dominant hypocalcemia: - Genetic Testing Registry: Autosomal dominant hypocalcemia These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | autosomal dominant hypocalcemia |
What is (are) PMM2-congenital disorder of glycosylation ? | PMM2-congenital disorder of glycosylation (PMM2-CDG, also known as congenital disorder of glycosylation type Ia) is an inherited condition that affects many parts of the body. The type and severity of problems associated with PMM2-CDG vary widely among affected individuals, sometimes even among members of the same family. Individuals with PMM2-CDG typically develop signs and symptoms of the condition during infancy. Affected infants may have weak muscle tone (hypotonia), retracted (inverted) nipples, an abnormal distribution of fat, eyes that do not look in the same direction (strabismus), developmental delay, and a failure to gain weight and grow at the expected rate (failure to thrive). Infants with PMM2-CDG also frequently have an underdeveloped cerebellum, which is the part of the brain that coordinates movement. Distinctive facial features are sometimes present in affected individuals, including a high forehead, a triangular face, large ears, and a thin upper lip. Children with PMM2-CDG may also have elevated liver function test results, seizures, fluid around the heart (pericardial effusion), and blood clotting disorders. About 20 percent of affected infants do not survive the first year of life due to multiple organ failure. The most severe cases of PMM2-CDG are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Most babies with hydrops fetalis are stillborn or die soon after birth. People with PMM2-CDG who survive infancy may have moderate intellectual disability, and some are unable to walk independently. Affected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. Recovery from these episodes usually occurs over a period of a few weeks to several months. During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and joint deformities (contractures). Some affected individuals have an eye disorder called retinitis pigmentosa that causes vision loss. Females with PMM2-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, females with PMM2-CDG do not go through puberty. Affected males experience normal puberty but often have small testes. | PMM2-congenital disorder of glycosylation |
How many people are affected by PMM2-congenital disorder of glycosylation ? | More than 800 individuals with PMM2-CDG have been identified worldwide. | PMM2-congenital disorder of glycosylation |
What are the genetic changes related to PMM2-congenital disorder of glycosylation ? | PMM2-CDG is caused by mutations in the PMM2 gene. This gene provides instructions for making an enzyme called phosphomannomutase 2 (PMM2). The PMM2 enzyme is involved in a process called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation modifies proteins so they can perform a wider variety of functions. Mutations in the PMM2 gene lead to the production of an abnormal PMM2 enzyme with reduced activity. Without a properly functioning PMM2 enzyme, glycosylation cannot proceed normally. As a result, incorrect oligosaccharides are produced and attached to proteins. The wide variety of signs and symptoms in PMM2-CDG are likely due to the production of abnormally glycosylated proteins in many organs and tissues. | PMM2-congenital disorder of glycosylation |
Is PMM2-congenital disorder of glycosylation inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | PMM2-congenital disorder of glycosylation |
What are the treatments for PMM2-congenital disorder of glycosylation ? | These resources address the diagnosis or management of PMM2-CDG: - Gene Review: Gene Review: PMM2-CDG (CDG-Ia) - Genetic Testing Registry: Carbohydrate-deficient glycoprotein syndrome type I These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | PMM2-congenital disorder of glycosylation |
What is (are) carnitine palmitoyltransferase I deficiency ? | Carnitine palmitoyltransferase I (CPT I) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). The severity of this condition varies among affected individuals. Signs and symptoms of CPT I deficiency often appear during early childhood. Affected individuals usually have low blood sugar (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. People with CPT I deficiency can also have an enlarged liver (hepatomegaly), liver malfunction, and elevated levels of carnitine in the blood. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. Individuals with CPT I deficiency are at risk for nervous system damage, liver failure, seizures, coma, and sudden death. Problems related to CPT I deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections. | carnitine palmitoyltransferase I deficiency |
How many people are affected by carnitine palmitoyltransferase I deficiency ? | CPT I deficiency is a rare disorder; fewer than 50 affected individuals have been identified. This disorder may be more common in the Hutterite and Inuit populations. | carnitine palmitoyltransferase I deficiency |
What are the genetic changes related to carnitine palmitoyltransferase I deficiency ? | Mutations in the CPT1A gene cause CPT I deficiency. This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 1A, which is found in the liver. Carnitine palmitoyltransferase 1A is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids cannot enter mitochondria unless they are attached to carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can enter mitochondria and be used to produce energy. During periods of fasting, long-chain fatty acids are an important energy source for the liver and other tissues. Mutations in the CPT1A gene severely reduce or eliminate the activity of carnitine palmitoyltransferase 1A. Without enough of this enzyme, carnitine is not attached to long-chain fatty acids. As a result, these fatty acids cannot enter mitochondria and be converted into energy. Reduced energy production can lead to some of the features of CPT I deficiency, such as hypoketotic hypoglycemia. Fatty acids may also build up in cells and damage the liver, heart, and brain. This abnormal buildup causes the other signs and symptoms of the disorder. | carnitine palmitoyltransferase I deficiency |
Is carnitine palmitoyltransferase I deficiency inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | carnitine palmitoyltransferase I deficiency |
What are the treatments for carnitine palmitoyltransferase I deficiency ? | These resources address the diagnosis or management of CPT I deficiency: - Baby's First Test - FOD (Fatty Oxidation Disorders) Family Support Group: Diagnostic Approach to Disorders of Fat Oxidation - Information for Clinicians - Gene Review: Gene Review: Carnitine Palmitoyltransferase 1A Deficiency - Genetic Testing Registry: Carnitine palmitoyltransferase I deficiency These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | carnitine palmitoyltransferase I deficiency |
What is (are) inherited thyroxine-binding globulin deficiency ? | Inherited thyroxine-binding globulin deficiency is a genetic condition that typically does not cause any health problems. Thyroxine-binding globulin is a protein that carries hormones made or used by the thyroid gland, which is a butterfly-shaped tissue in the lower neck. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). Most of the time, these hormones circulate in the bloodstream attached to thyroxine-binding globulin and similar proteins. If there is a shortage (deficiency) of thyroxine-binding globulin, the amount of circulating thyroid hormones is reduced. Researchers have identified two forms of inherited thyroxine-binding globulin deficiency: the complete form (TBG-CD), which results in a total loss of thyroxine-binding globulin, and the partial form (TBG-PD), which reduces the amount of this protein or alters its structure. Neither of these conditions causes any problems with thyroid function. They are usually identified during routine blood tests that measure thyroid hormones. Although inherited thyroxine-binding globulin deficiency does not cause any health problems, it can be mistaken for more serious thyroid disorders (such as hypothyroidism). Therefore, it is important to diagnose inherited thyroxine-binding globulin deficiency to avoid unnecessary treatments. | inherited thyroxine-binding globulin deficiency |
How many people are affected by inherited thyroxine-binding globulin deficiency ? | The complete form of inherited thyroxine-binding globulin deficiency, TBG-CD, affects about 1 in 15,000 newborns worldwide. The partial form, TBG-PD, affects about 1 in 4,000 newborns. These conditions appear to be more common in the Australian Aborigine population and in the Bedouin population of southern Israel. | inherited thyroxine-binding globulin deficiency |
What are the genetic changes related to inherited thyroxine-binding globulin deficiency ? | Inherited thyroxine-binding globulin deficiency results from mutations in the SERPINA7 gene. This gene provides instructions for making thyroxine-binding globulin. Some mutations in the SERPINA7 gene prevent the production of a functional protein, causing TBG-CD. Other mutations reduce the amount of this protein or alter its structure, resulting in TBG-PD. Researchers have also described non-inherited forms of thyroxine-binding globulin deficiency, which are more common than the inherited form. Non-inherited thyroxine-binding globulin deficiency can occur with a variety of illnesses and is a side effect of some medications. | inherited thyroxine-binding globulin deficiency |
Is inherited thyroxine-binding globulin deficiency inherited ? | Inherited thyroxine-binding globulin deficiency has an X-linked pattern of inheritance. The SERPINA7 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes partial or complete inherited thyroxine-binding globulin deficiency. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell reduces the amount of thyroxine-binding globulin. However, their levels of this protein are usually within the normal range. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. | inherited thyroxine-binding globulin deficiency |
What are the treatments for inherited thyroxine-binding globulin deficiency ? | These resources address the diagnosis or management of inherited thyroxine-binding globulin deficiency: - American Thyroid Association: Thyroid Function Tests - MedlinePlus Encyclopedia: Serum TBG Level These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | inherited thyroxine-binding globulin deficiency |
What is (are) dyserythropoietic anemia and thrombocytopenia ? | Dyserythropoietic anemia and thrombocytopenia is a condition that affects blood cells and primarily occurs in males. A main feature of this condition is a type of anemia called dyserythropoietic anemia, which is characterized by a shortage of red blood cells. The term "dyserythropoietic" refers to the abnormal red blood cell formation that occurs in this condition. In affected individuals, immature red blood cells are unusually shaped and cannot develop into functional mature cells, leading to a shortage of healthy red blood cells. People with dyserythropoietic anemia and thrombocytopenia can have another blood disorder characterized by a reduced level of circulating platelets (thrombocytopenia). Platelets are cell fragments that normally assist with blood clotting. Thrombocytopenia can cause easy bruising and abnormal bleeding. While people with dyserythropoietic anemia and thrombocytopenia can have signs and symptoms of both blood disorders, some are primarily affected by anemia, while others are more affected by thrombocytopenia. The most severe cases of dyserythropoietic anemia and thrombocytopenia are characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. For many others, the signs and symptoms of dyserythropoietic anemia and thrombocytopenia begin in infancy. People with this condition experience prolonged bleeding or bruising after minor trauma or even in the absence of injury (spontaneous bleeding). Anemia can cause pale skin, weakness, and fatigue. Severe anemia may create a need for frequent blood transfusions to replenish the supply of red blood cells; however, repeated blood transfusions over many years can cause health problems such as excess iron in the blood. People with dyserythropoietic anemia and thrombocytopenia may also have a shortage of white blood cells (neutropenia), which can make them prone to recurrent infections. Additionally, they may have an enlarged spleen (splenomegaly). The severity of these abnormalities varies among affected individuals. Some people with dyserythropoietic anemia and thrombocytopenia have additional blood disorders such as beta thalassemia or congenital erythropoietic porphyria. Beta thalassemia is a condition that reduces the production of hemoglobin, which is the iron-containing protein in red blood cells that carries oxygen. A decrease in hemoglobin can lead to a shortage of oxygen in cells and tissues throughout the body. Congenital erythropoietic porphyria is another disorder that impairs hemoglobin production. People with congenital erythropoietic porphyria are also very sensitive to sunlight, and areas of skin exposed to the sun can become fragile and blistered. | dyserythropoietic anemia and thrombocytopenia |
How many people are affected by dyserythropoietic anemia and thrombocytopenia ? | Dyserythropoietic anemia and thrombocytopenia is a rare condition; its prevalence is unknown. Occasionally, individuals with this disorder are mistakenly diagnosed as having more common blood disorders, making it even more difficult to determine how many people have dyserythropoietic anemia and thrombocytopenia. | dyserythropoietic anemia and thrombocytopenia |
What are the genetic changes related to dyserythropoietic anemia and thrombocytopenia ? | Mutations in the GATA1 gene cause dyserythropoietic anemia and thrombocytopenia. The GATA1 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and helps control the activity of many other genes. On the basis of this action, the GATA1 protein is known as a transcription factor. The GATA1 protein is involved in the specialization (differentiation) of immature blood cells. To function properly, these immature cells must differentiate into specific types of mature blood cells. Through its activity as a transcription factor and its interactions with other proteins, the GATA1 protein regulates the growth and division (proliferation) of immature red blood cells and platelet-precursor cells (megakaryocytes) and helps with their differentiation. GATA1 gene mutations disrupt the protein's ability to bind with DNA or interact with other proteins. These impairments in the GATA1 protein's normal function result in an increased proliferation of megakaryocytes and a decrease in mature platelets, leading to abnormal bleeding. An abnormal GATA1 protein causes immature red blood cells to undergo a form of programmed cell death called apoptosis. A lack of immature red blood cells results in decreased amounts of specialized, mature red blood cells, leading to anemia. The severity of dyserythropoietic anemia and thrombocytopenia can usually be predicted by the type of GATA1 gene mutation. When the two blood disorders dyserythropoietic anemia and thrombocytopenia occur separately, each of the conditions can result from many different factors. The occurrence of these disorders together is characteristic of mutations in the GATA1 gene. | dyserythropoietic anemia and thrombocytopenia |
Is dyserythropoietic anemia and thrombocytopenia inherited ? | This condition is inherited in an X-linked pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes in each cell. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males or may cause no symptoms in females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. | dyserythropoietic anemia and thrombocytopenia |
What are the treatments for dyserythropoietic anemia and thrombocytopenia ? | These resources address the diagnosis or management of dyserythropoietic anemia and thrombocytopenia: - Gene Review: Gene Review: GATA1-Related X-Linked Cytopenia - Genetic Testing Registry: GATA-1-related thrombocytopenia with dyserythropoiesis These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | dyserythropoietic anemia and thrombocytopenia |
What is (are) Lafora progressive myoclonus epilepsy ? | Lafora progressive myoclonus epilepsy is a brain disorder characterized by recurrent seizures (epilepsy) and a decline in intellectual function. The signs and symptoms of the disorder usually appear in late childhood or adolescence and worsen with time. Myoclonus is a term used to describe episodes of sudden, involuntary muscle jerking or twitching that can affect part of the body or the entire body. Myoclonus can occur when an affected person is at rest, and it is made worse by motion, excitement, or flashing light (photic stimulation). In the later stages of Lafora progressive myoclonus epilepsy, myoclonus often occurs continuously and affects the entire body. Several types of seizures commonly occur in people with Lafora progressive myoclonus epilepsy. Generalized tonic-clonic seizures (also known as grand mal seizures) affect the entire body, causing muscle rigidity, convulsions, and loss of consciousness. Affected individuals may also experience occipital seizures, which can cause temporary blindness and visual hallucinations. Over time, the seizures worsen and become more difficult to treat. A life-threatening seizure condition called status epilepticus may also develop. Status epilepticus is a continuous state of seizure activity lasting longer than several minutes. About the same time seizures begin, intellectual function starts to decline. Behavioral changes, depression, confusion, and speech difficulties (dysarthria) are among the early signs and symptoms of this disorder. As the condition progresses, a continued loss of intellectual function (dementia) impairs memory, judgment, and thought. Affected people lose the ability to perform the activities of daily living by their mid-twenties, and they ultimately require comprehensive care. People with Lafora progressive myoclonus epilepsy generally survive up to 10 years after symptoms first appear. | Lafora progressive myoclonus epilepsy |
How many people are affected by Lafora progressive myoclonus epilepsy ? | The prevalence of Lafora progressive myoclonus epilepsy is unknown. Although the condition occurs worldwide, it appears to be most common in Mediterranean countries (including Spain, France, and Italy), parts of Central Asia, India, Pakistan, North Africa, and the Middle East. | Lafora progressive myoclonus epilepsy |
What are the genetic changes related to Lafora progressive myoclonus epilepsy ? | Lafora progressive myoclonus epilepsy can be caused by mutations in either the EPM2A gene or the NHLRC1 gene. These genes provide instructions for making proteins called laforin and malin, respectively. Laforin and malin play a critical role in the survival of nerve cells (neurons) in the brain. Studies suggest that laforin and malin work together and may have several functions. One of these is to help regulate the production of a complex sugar called glycogen, which is a major source of stored energy in the body. The body stores this sugar in the liver and muscles, breaking it down when it is needed for fuel. Laforin and malin may prevent a potentially damaging buildup of glycogen in tissues that do not normally store this molecule, such as those of the nervous system. Researchers have discovered that people with Lafora progressive myoclonus epilepsy have distinctive clumps called Lafora bodies within their cells. Lafora bodies are made up of an abnormal form of glycogen that cannot be broken down and used for fuel. Instead, it builds up to form clumps that can damage cells. Neurons appear to be particularly vulnerable to this type of damage. Although Lafora bodies are found in many of the body's tissues, the signs and symptoms of Lafora progressive myoclonus epilepsy are limited to the nervous system. Mutations in the EPM2A gene prevent cells from making functional laforin, while NHLRC1 gene mutations prevent the production of functional malin. It is unclear how a loss of either of these proteins leads to the formation of Lafora bodies. However, a loss of laforin or malin ultimately results in the death of neurons, which interferes with the brain's normal functions. The condition tends to progress more slowly in some people with NHLRC1 gene mutations than in those with EPM2A gene mutations. Mutations in the EPM2A and NHLRC1 genes account for 80 percent to 90 percent of all cases of Lafora progressive myoclonus epilepsy. In the remaining cases, the cause of the condition is unknown. Researchers are searching for other genetic changes that may underlie this disease. | Lafora progressive myoclonus epilepsy |
Is Lafora progressive myoclonus epilepsy inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | Lafora progressive myoclonus epilepsy |
What are the treatments for Lafora progressive myoclonus epilepsy ? | These resources address the diagnosis or management of Lafora progressive myoclonus epilepsy: - Gene Review: Gene Review: Progressive Myoclonus Epilepsy, Lafora Type - Genetic Testing Registry: Lafora disease - MedlinePlus Encyclopedia: Epilepsy - MedlinePlus Encyclopedia:Generalized Tonic-Clonic Seizure These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Lafora progressive myoclonus epilepsy |
What is (are) mucopolysaccharidosis type I ? | Mucopolysaccharidosis type I (MPS I) is a condition that affects many parts of the body. This disorder was once divided into three separate syndromes: Hurler syndrome (MPS I-H), Hurler-Scheie syndrome (MPS I-H/S), and Scheie syndrome (MPS I-S), listed from most to least severe. Because there is so much overlap between each of these three syndromes, MPS I is currently divided into the severe and attenuated types. Children with MPS I often have no signs or symptoms of the condition at birth, although some have a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with severe MPS I generally begin to show other signs and symptoms of the disorder within the first year of life, while those with the attenuated form have milder features that develop later in childhood. Individuals with MPS I may have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), heart valve abnormalities, distinctive-looking facial features that are described as "coarse," an enlarged liver and spleen (hepatosplenomegaly), and a large tongue (macroglossia). Vocal cords can also enlarge, resulting in a deep, hoarse voice. The airway may become narrow in some people with MPS I, causing frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). People with MPS I often develop clouding of the clear covering of the eye (cornea), which can cause significant vision loss. Affected individuals may also have hearing loss and recurrent ear infections. Some individuals with MPS I have short stature and joint deformities (contractures) that affect mobility. Most people with the severe form of the disorder also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord. While both forms of MPS I can affect many different organs and tissues, people with severe MPS I experience a decline in intellectual function and a more rapid disease progression. Developmental delay is usually present by age 1, and severely affected individuals eventually lose basic functional skills (developmentally regress). Children with this form of the disorder usually have a shortened lifespan, sometimes living only into late childhood. Individuals with attenuated MPS I typically live into adulthood and may or may not have a shortened lifespan. Some people with the attenuated type have learning disabilities, while others have no intellectual impairments. Heart disease and airway obstruction are major causes of death in people with both types of MPS I. | mucopolysaccharidosis type I |
How many people are affected by mucopolysaccharidosis type I ? | Severe MPS I occurs in approximately 1 in 100,000 newborns. Attenuated MPS I is less common and occurs in about 1 in 500,000 newborns. | mucopolysaccharidosis type I |
What are the genetic changes related to mucopolysaccharidosis type I ? | Mutations in the IDUA gene cause MPS I. The IDUA gene provides instructions for producing an enzyme that is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). GAGs were originally called mucopolysaccharides, which is where this condition gets its name. Mutations in the IDUA gene reduce or completely eliminate the function of the IDUA enzyme. The lack of IDUA enzyme activity leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions that cause molecules to build up inside the lysosomes, including MPS I, are called lysosomal storage disorders. The accumulation of GAGs increases the size of the lysosomes, which is why many tissues and organs are enlarged in this disorder. Researchers believe that the GAGs may also interfere with the functions of other proteins inside the lysosomes and disrupt the movement of molecules inside the cell. | mucopolysaccharidosis type I |
Is mucopolysaccharidosis type I inherited ? | This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. | mucopolysaccharidosis type I |
What are the treatments for mucopolysaccharidosis type I ? | These resources address the diagnosis or management of mucopolysaccharidosis type I: - Baby's First Test - Gene Review: Gene Review: Mucopolysaccharidosis Type I - Genetic Testing Registry: Mucopolysaccharidosis type I - MedlinePlus Encyclopedia: Hurler Syndrome - MedlinePlus Encyclopedia: Mucopolysaccharides - MedlinePlus Encyclopedia: Scheie Syndrome - National MPS Society: Treatments These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | mucopolysaccharidosis type I |
What is (are) Langer mesomelic dysplasia ? | Langer mesomelic dysplasia is a disorder of bone growth. Affected individuals typically have extreme shortening of the long bones in the arms and legs (mesomelia). As a result of the shortened leg bones, people with Langer mesomelic dysplasia have very short stature. A bone in the forearm called the ulna and a bone in the lower leg called the fibula are often underdeveloped or absent, while other bones in the forearm (the radius) and lower leg (the tibia) are unusually short, thick, and curved. Some people with Langer mesomelic dysplasia also have an abnormality of the wrist and forearm bones called Madelung deformity, which may cause pain and limit wrist movement. Additionally, some affected individuals have mild underdevelopment of the lower jaw bone (mandible). | Langer mesomelic dysplasia |
How many people are affected by Langer mesomelic dysplasia ? | The prevalence of Langer mesomelic dysplasia is unknown, although the condition appears to be rare. Several dozen affected individuals have been reported in the scientific literature. | Langer mesomelic dysplasia |
What are the genetic changes related to Langer mesomelic dysplasia ? | Langer mesomelic dysplasia results from changes involving the SHOX gene. The protein produced from this gene plays a role in bone development and is particularly important for the growth and maturation of bones in the arms and legs. The most common cause of Langer mesomelic dysplasia is a deletion of the entire SHOX gene. Other genetic changes that can cause the disorder include mutations in the SHOX gene or deletions of nearby genetic material that normally helps regulate the gene's activity. These changes greatly reduce or eliminate the amount of SHOX protein that is produced. A lack of this protein disrupts normal bone development and growth, which underlies the severe skeletal abnormalities associated with Langer mesomelic dysplasia. | Langer mesomelic dysplasia |
Is Langer mesomelic dysplasia inherited ? | Langer mesomelic dysplasia has a pseudoautosomal recessive pattern of inheritance. The SHOX gene is located on both the X and Y chromosomes (sex chromosomes) in an area known as the pseudoautosomal region. Although many genes are unique to either the X or Y chromosome, genes in the pseudoautosomal region are present on both sex chromosomes. As a result, both females (who have two X chromosomes) and males (who have one X and one Y chromosome) normally have two functional copies of the SHOX gene in each cell. The inheritance pattern of Langer mesomelic dysplasia is described as recessive because both copies of the SHOX gene in each cell must be missing or altered to cause the disorder. In females, the condition results when the gene is missing or altered on both copies of the X chromosome; in males, it results when the gene is missing or altered on the X chromosome and the Y chromosome. A related skeletal disorder called Lri-Weill dyschondrosteosis occurs when one copy of the SHOX gene is mutated in each cell. This disorder has signs and symptoms that are similar to, but typically less severe than, those of Langer mesomelic dysplasia. | Langer mesomelic dysplasia |
What are the treatments for Langer mesomelic dysplasia ? | These resources address the diagnosis or management of Langer mesomelic dysplasia: - Genetic Testing Registry: Langer mesomelic dysplasia syndrome These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Langer mesomelic dysplasia |
What is (are) Legius syndrome ? | Legius syndrome is a condition characterized by changes in skin coloring (pigmentation). Almost all affected individuals have multiple caf-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Another pigmentation change, freckles in the armpits and groin, may occur in some affected individuals. Other signs and symptoms of Legius syndrome may include an abnormally large head (macrocephaly) and unusual facial characteristics. Although most people with Legius syndrome have normal intelligence, some affected individuals have been diagnosed with learning disabilities, attention deficit disorder (ADD), or attention deficit hyperactivity disorder (ADHD). Many of the signs and symptoms of Legius syndrome also occur in a similar disorder called neurofibromatosis type 1. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life. | Legius syndrome |
How many people are affected by Legius syndrome ? | The prevalence of Legius syndrome is unknown. Many individuals with this disorder are likely misdiagnosed because the signs and symptoms of Legius syndrome are similar to those of neurofibromatosis type 1. | Legius syndrome |
What are the genetic changes related to Legius syndrome ? | Mutations in the SPRED1 gene cause Legius syndrome. The SPRED1 gene provides instructions for making the Spred-1 protein. This protein controls (regulates) an important cell signaling pathway that is involved in the growth and division of cells (proliferation), the process by which cells mature to carry out specific functions (differentiation), cell movement, and the self-destruction of cells (apoptosis). Mutations in the SPRED1 gene lead to a nonfunctional protein that can no longer regulate the pathway, resulting in overactive signaling. It is unclear how mutations in the SPRED1 gene cause the signs and symptoms of Legius syndrome. | Legius syndrome |
Is Legius syndrome inherited ? | This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. | Legius syndrome |
What are the treatments for Legius syndrome ? | These resources address the diagnosis or management of Legius syndrome: - Children's Tumor Foundation: NF1 or Legius Syndrome--An Emerging Challenge of Clinical Diagnosis - Gene Review: Gene Review: Legius Syndrome - Genetic Testing Registry: Legius syndrome These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Legius syndrome |
What is (are) Huntington disease ? | Huntington disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and loss of thinking ability (cognition). Adult-onset Huntington disease, the most common form of this disorder, usually appears in a person's thirties or forties. Early signs and symptoms can include irritability, depression, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many people with Huntington disease develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these movements become more pronounced. Affected individuals may have trouble walking, speaking, and swallowing. People with this disorder also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with the adult-onset form of Huntington disease usually live about 15 to 20 years after signs and symptoms begin. A less common form of Huntington disease known as the juvenile form begins in childhood or adolescence. It also involves movement problems and mental and emotional changes. Additional signs of the juvenile form include slow movements, clumsiness, frequent falling, rigidity, slurred speech, and drooling. School performance declines as thinking and reasoning abilities become impaired. Seizures occur in 30 percent to 50 percent of children with this condition. Juvenile Huntington disease tends to progress more quickly than the adult-onset form; affected individuals usually live 10 to 15 years after signs and symptoms appear. | Huntington disease |
How many people are affected by Huntington disease ? | Huntington disease affects an estimated 3 to 7 per 100,000 people of European ancestry. The disorder appears to be less common in some other populations, including people of Japanese, Chinese, and African descent. | Huntington disease |
What are the genetic changes related to Huntington disease ? | Mutations in the HTT gene cause Huntington disease. The HTT gene provides instructions for making a protein called huntingtin. Although the function of this protein is unknown, it appears to play an important role in nerve cells (neurons) in the brain. The HTT mutation that causes Huntington disease involves a DNA segment known as a CAG trinucleotide repeat. This segment is made up of a series of three DNA building blocks (cytosine, adenine, and guanine) that appear multiple times in a row. Normally, the CAG segment is repeated 10 to 35 times within the gene. In people with Huntington disease, the CAG segment is repeated 36 to more than 120 times. People with 36 to 39 CAG repeats may or may not develop the signs and symptoms of Huntington disease, while people with 40 or more repeats almost always develop the disorder. An increase in the size of the CAG segment leads to the production of an abnormally long version of the huntingtin protein. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal functions of these cells. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of Huntington disease. | Huntington disease |
Is Huntington disease inherited ? | This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. An affected person usually inherits the altered gene from one affected parent. In rare cases, an individual with Huntington disease does not have a parent with the disorder. As the altered HTT gene is passed from one generation to the next, the size of the CAG trinucleotide repeat often increases in size. A larger number of repeats is usually associated with an earlier onset of signs and symptoms. This phenomenon is called anticipation. People with the adult-onset form of Huntington disease typically have 40 to 50 CAG repeats in the HTT gene, while people with the juvenile form of the disorder tend to have more than 60 CAG repeats. Individuals who have 27 to 35 CAG repeats in the HTT gene do not develop Huntington disease, but they are at risk of having children who will develop the disorder. As the gene is passed from parent to child, the size of the CAG trinucleotide repeat may lengthen into the range associated with Huntington disease (36 repeats or more). | Huntington disease |
What are the treatments for Huntington disease ? | These resources address the diagnosis or management of Huntington disease: - Gene Review: Gene Review: Huntington Disease - Genetic Testing Registry: Huntington's chorea - Huntington's Disease Society of America: HD Care - MedlinePlus Encyclopedia: Huntington Disease - University of Washington Medical Center: Testing for Huntington Disease: Making an Informed Choice These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | Huntington disease |
What is (are) familial thoracic aortic aneurysm and dissection ? | Familial thoracic aortic aneurysm and dissection (familial TAAD) involves problems with the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. Familial TAAD affects the upper part of the aorta, near the heart. This part of the aorta is called the thoracic aorta because it is located in the chest (thorax). Other vessels that carry blood from the heart to the rest of the body (arteries) can also be affected. In familial TAAD, the aorta can become weakened and stretched (aortic dilatation), which can lead to a bulge in the blood vessel wall (an aneurysm). Aortic dilatation may also lead to a sudden tearing of the layers in the aorta wall (aortic dissection), allowing blood to flow abnormally between the layers. These aortic abnormalities are potentially life-threatening because they can decrease blood flow to other parts of the body such as the brain or other vital organs, or cause the aorta to break open (rupture). The occurrence and timing of these aortic abnormalities vary, even within the same affected family. They can begin in childhood or not occur until late in life. Aortic dilatation is generally the first feature of familial TAAD to develop, although in some affected individuals dissection occurs with little or no aortic dilatation. Aortic aneurysms usually have no symptoms. However, depending on the size, growth rate, and location of these abnormalities, they can cause pain in the jaw, neck, chest, or back; swelling in the arms, neck, or head; difficult or painful swallowing; hoarseness; shortness of breath; wheezing; a chronic cough; or coughing up blood. Aortic dissections usually cause severe, sudden chest or back pain, and may also result in unusually pale skin (pallor), a very faint pulse, numbness or tingling (paresthesias) in one or more limbs, or paralysis. Familial TAAD may not be associated with other signs and symptoms. However, some individuals in affected families show mild features of related conditions called Marfan syndrome or Loeys-Dietz syndrome. These features include tall stature, stretch marks on the skin, an unusually large range of joint movement (joint hypermobility), and either a sunken or protruding chest. Occasionally, people with familial TAAD develop aneurysms in the brain or in the section of the aorta located in the abdomen (abdominal aorta). Some people with familial TAAD have heart abnormalities that are present from birth (congenital). Affected individuals may also have a soft out-pouching in the lower abdomen (inguinal hernia), an abnormal curvature of the spine (scoliosis), or a purplish skin discoloration (livedo reticularis) caused by abnormalities in the tiny blood vessels of the skin (dermal capillaries). However, these conditions are also common in the general population. Depending on the genetic cause of familial TAAD in particular families, they may have an increased risk of developing blockages in smaller arteries, which can lead to heart attack and stroke. | familial thoracic aortic aneurysm and dissection |
How many people are affected by familial thoracic aortic aneurysm and dissection ? | Familial TAAD is believed to account for at least 20 percent of thoracic aortic aneurysms and dissections. In the remainder of cases, the abnormalities are thought to be caused by factors that are not inherited, such as damage to the walls of the aorta from aging, tobacco use, injury, or disease. While aortic aneurysms are common worldwide, it is difficult to determine their exact prevalence because they usually cause no symptoms unless they rupture. Ruptured aortic aneurysms and dissections are estimated to cause almost 30,000 deaths in the United States each year. | familial thoracic aortic aneurysm and dissection |
What are the genetic changes related to familial thoracic aortic aneurysm and dissection ? | Mutations in any of several genes are associated with familial TAAD. Mutations in the ACTA2 gene have been identified in 14 to 20 percent of people with this disorder, and TGFBR2 gene mutations have been found in 2.5 percent of affected individuals. Mutations in several other genes account for smaller percentages of cases. The ACTA2 gene provides instructions for making a protein called smooth muscle alpha ()-2 actin, which is found in vascular smooth muscle cells. Layers of these cells are found in the walls of the aorta and other arteries. Within vascular smooth muscle cells, smooth muscle -2 actin forms the core of structures called sarcomeres, which are necessary for muscles to contract. This ability to contract allows the arteries to maintain their shape instead of stretching out as blood is pumped through them. ACTA2 gene mutations that are associated with familial TAAD change single protein building blocks (amino acids) in the smooth muscle -2 actin protein. These changes likely affect the way the protein functions in smooth muscle contraction, interfering with the sarcomeres' ability to prevent the arteries from stretching. The aorta, where the force of blood pumped directly from the heart is most intense, is particularly vulnerable to this stretching. Abnormal stretching of the aorta results in the aortic dilatation, aneurysms, and dissections that characterize familial TAAD. TGFBR2 gene mutations are also associated with familial TAAD. The TGFBR2 gene provides instructions for making a protein called transforming growth factor-beta (TGF-) receptor type 2. This receptor transmits signals from the cell surface into the cell through a process called signal transduction. Through this type of signaling, the environment outside the cell affects activities inside the cell. In particular, the TGF- receptor type 2 protein helps control the growth and division (proliferation) of cells and the process by which cells mature to carry out specific functions (differentiation). It is also involved in the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells. TGFBR2 gene mutations alter the receptor's structure, which disturbs signal transduction. The disturbed signaling can impair cell growth and development. It is not known how these changes result in the specific aortic abnormalities associated with familial TAAD. Mutations in other genes, some of which have not been identified, are also associated with familial TAAD. | familial thoracic aortic aneurysm and dissection |
Is familial thoracic aortic aneurysm and dissection inherited ? | Familial TAAD is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell can be sufficient to cause the condition. In most cases, an affected person has one affected parent. However, some people who inherit an altered gene never develop the aortic abnormalities associated with the condition; this situation is known as reduced penetrance. | familial thoracic aortic aneurysm and dissection |
What are the treatments for familial thoracic aortic aneurysm and dissection ? | These resources address the diagnosis or management of familial TAAD: - Gene Review: Gene Review: Thoracic Aortic Aneurysms and Aortic Dissections - Genetic Testing Registry: Aortic aneurysm, familial thoracic 2 - Genetic Testing Registry: Aortic aneurysm, familial thoracic 4 - Genetic Testing Registry: Aortic aneurysm, familial thoracic 6 - Genetic Testing Registry: Congenital aneurysm of ascending aorta - Genetic Testing Registry: Thoracic aortic aneurysm and aortic dissection These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care | familial thoracic aortic aneurysm and dissection |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.