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What is (are) Nijmegen breakage syndrome ? | Nijmegen breakage syndrome is a condition characterized by short stature, an unusually small head size (microcephaly), distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, intellectual disability, and other health problems. People with this condition typically grow slowly during infancy and early childhood. After this period of slow growth, affected individuals grow at a normal rate but remain shorter than their peers. Microcephaly is apparent from birth in the majority of affected individuals. The head does not grow at the same rate as the rest of the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Individuals with Nijmegen breakage syndrome have distinctive facial features that include a sloping forehead, a prominent nose, large ears, a small jaw, and outside corners of the eyes that point upward (upslanting palpebral fissures). These facial features typically become apparent by age 3. People with Nijmegen breakage syndrome have a malfunctioning immune system (immunodeficiency) with abnormally low levels of immune system proteins called immunoglobulin G (IgG) and immunoglobulin A (IgA). Affected individuals also have a shortage of immune system cells called T cells. The immune system abnormalities increase susceptibility to recurrent infections, such as bronchitis, pneumonia, sinusitis, and other infections affecting the upper respiratory tract and lungs. Individuals with Nijmegen breakage syndrome have an increased risk of developing cancer, most commonly a cancer of immune system cells called non-Hodgkin lymphoma. About half of individuals with Nijmegen breakage syndrome develop non-Hodgkin lymphoma, usually before age 15. Other cancers seen in people with Nijmegen breakage syndrome include brain tumors such as medulloblastoma and glioma, and a cancer of muscle tissue called rhabdomyosarcoma. People with Nijmegen breakage syndrome are 50 times more likely to develop cancer than people without this condition. Intellectual development is normal in most people with this condition for the first year or two of life, but then development becomes delayed. Skills decline over time, and most affected children and adults have mild to moderate intellectual disability. Most affected woman have premature ovarian failure and do not begin menstruation by age 16 (primary amenorrhea) or have infrequent menstrual periods. Most women with Nijmegen breakage syndrome are unable to have biological children (infertile). | Nijmegen breakage syndrome |
How many people are affected by Nijmegen breakage syndrome ? | The exact prevalence of Nijmegen breakage syndrome is unknown. This condition is estimated to affect one in 100,000 newborns worldwide, but is thought to be most common in the Slavic populations of Eastern Europe. | Nijmegen breakage syndrome |
What are the genetic changes related to Nijmegen breakage syndrome ? | Mutations in the NBN gene cause Nijmegen breakage syndrome. The NBN gene provides instructions for making a protein called nibrin. This protein is involved in several critical cellular functions, including the repair of damaged DNA. Nibrin interacts with two other proteins as part of a larger protein complex. This protein complex works to mend broken strands of DNA. DNA can be damaged by agents such as toxic chemicals or radiation. Breaks in DNA strands also occur naturally when chromosomes exchange genetic material in preparation for cell division. Repairing DNA prevents cells from accumulating genetic damage that can cause them to die or to divide uncontrollably. The nibrin protein and the proteins with which it interacts help maintain the stability of a cell's genetic information through its roles in repairing damaged DNA and regulating cell division. The NBN gene mutations that cause this condition typically lead to the production of an abnormally short version of the nibrin protein. The defective protein is missing important regions, preventing it from responding to DNA damage effectively. As a result, affected individuals are sensitive to the effects of radiation exposure and other agents that can cause breaks in DNA. Nijmegen breakage syndrome gets its name from numerous breaks in DNA that occur in affected people's cells. A buildup of mistakes in DNA can trigger cells to grow and divide abnormally, increasing the risk of cancer in people with Nijmegen breakage syndrome. Nibrin's role in regulating cell division and cell growth (proliferation) is thought to lead to the immunodeficiency seen in affected individuals. A lack of functional nibrin results in less immune cell proliferation. A decrease in the amount of immune cells that are produced leads to reduced amounts of immunoglobulins and other features of immunodeficiency. It is unclear how mutations in the NBN gene cause the other features of Nijmegen breakage syndrome. | Nijmegen breakage syndrome |
Is Nijmegen breakage syndrome 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. | Nijmegen breakage syndrome |
What are the treatments for Nijmegen breakage syndrome ? | These resources address the diagnosis or management of Nijmegen breakage syndrome: - Boston Children's Hospital: Pneumonia in Children - Boston Children's Hospital: Sinusitis in Children - Cleveland Clinic: Bronchitis - Gene Review: Gene Review: Nijmegen Breakage Syndrome - Genetic Testing Registry: Microcephaly, normal intelligence and immunodeficiency 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 | Nijmegen breakage syndrome |
What is (are) Gorlin syndrome ? | Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a condition that affects many areas of the body and increases the risk of developing various cancerous and noncancerous tumors. In people with Gorlin syndrome, the type of cancer diagnosed most often is basal cell carcinoma, which is the most common form of skin cancer. Individuals with Gorlin syndrome typically begin to develop basal cell carcinomas during adolescence or early adulthood. These cancers occur most often on the face, chest, and back. The number of basal cell carcinomas that develop during a person's lifetime varies among affected individuals. Some people with Gorlin syndrome never develop any basal cell carcinomas, while others may develop thousands of these cancers. Individuals with lighter skin are more likely to develop basal cell carcinomas than are people with darker skin. Most people with Gorlin syndrome also develop noncancerous (benign) tumors of the jaw, called keratocystic odontogenic tumors. These tumors usually first appear during adolescence, and new tumors form until about age 30. Keratocystic odontogenic tumors rarely develop later in adulthood. If untreated, these tumors may cause painful facial swelling and tooth displacement. Individuals with Gorlin syndrome have a higher risk than the general population of developing other tumors. A small proportion of affected individuals develop a brain tumor called medulloblastoma during childhood. A type of benign tumor called a fibroma can occur in the heart or in a woman's ovaries. Heart (cardiac) fibromas often do not cause any symptoms, but they may obstruct blood flow or cause irregular heartbeats (arrhythmia). Ovarian fibromas are not thought to affect a woman's ability to have children (fertility). Other features of Gorlin syndrome include small depressions (pits) in the skin of the palms of the hands and soles of the feet; an unusually large head size (macrocephaly) with a prominent forehead; and skeletal abnormalities involving the spine, ribs, or skull. These signs and symptoms are typically apparent from birth or become evident in early childhood. | Gorlin syndrome |
How many people are affected by Gorlin syndrome ? | Gorlin syndrome affects an estimated 1 in 31,000 people. While more than 1 million new cases of basal cell carcinoma are diagnosed each year in the United States, fewer than 1 percent of these skin cancers are related to Gorlin syndrome. | Gorlin syndrome |
What are the genetic changes related to Gorlin syndrome ? | Mutations in the PTCH1 gene cause Gorlin syndrome. This gene provides instructions for making a protein called patched-1, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function. A protein called Sonic Hedgehog is the ligand for the patched-1 receptor. Patched-1 blocks cell growth and division (proliferation) until Sonic Hedgehog is attached. The PTCH1 gene is a tumor suppressor gene, which means it stops cells from proliferating too rapidly or in an uncontrolled way. Mutations in this gene prevent the production of patched-1 or lead to the production of an abnormal version of the receptor. An altered or missing patched-1 receptor cannot effectively suppress cell growth and division. As a result, cells proliferate uncontrollably to form the tumors that are characteristic of Gorlin syndrome. It is less clear how PTCH1 gene mutations cause the other signs and symptoms related to this condition. The characteristic features of Gorlin syndrome can also be associated with a chromosomal change called a 9q22.3 microdeletion, in which a small piece of chromosome 9 is deleted in each cell. This deletion includes the segment of chromosome 9 that contains the PTCH1 gene, and as a result, people with a 9q22.3 microdeletion are missing one copy of this gene. Loss of this gene underlies the signs and symptoms of Gorlin syndrome in people with 9q22.3 microdeletions. Affected individuals also have features that are not typically associated with Gorlin syndrome, including delayed development, intellectual disability, overgrowth of the body (macrosomia), and other physical abnormalities. Researchers believe that these other signs and symptoms may result from the loss of additional genes in the deleted region of chromosome 9. | Gorlin syndrome |
Is Gorlin syndrome inherited ? | Gorlin syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the condition. In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the PTCH1 gene and occur in people with no history of the disorder in their family. Having one mutated copy of the PTCH1 gene in each cell is enough to cause the features of Gorlin syndrome that are present early in life, including macrocephaly and skeletal abnormalities. For basal cell carcinomas and other tumors to develop, a mutation in the second copy of the PTCH1 gene must also occur in certain cells during the person's lifetime. Most people who are born with one PTCH1 gene mutation eventually acquire a second mutation in some cells and consequently develop various types of tumors. | Gorlin syndrome |
What are the treatments for Gorlin syndrome ? | These resources address the diagnosis or management of Gorlin syndrome: - Gene Review: Gene Review: Nevoid Basal Cell Carcinoma Syndrome - Genetic Testing Registry: Gorlin syndrome - MedlinePlus Encyclopedia: Basal Cell Nevus 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 | Gorlin syndrome |
What is (are) PDGFRA-associated chronic eosinophilic leukemia ? | PDGFRA-associated chronic eosinophilic leukemia is a form of blood cell cancer characterized by an elevated number of cells called eosinophils in the blood. These cells help fight infections by certain parasites and are involved in the inflammation associated with allergic reactions. However, these circumstances do not account for the increased number of eosinophils in PDGFRA-associated chronic eosinophilic leukemia. Another characteristic feature of PDGFRA-associated chronic eosinophilic leukemia is organ damage caused by the excess eosinophils. Eosinophils release substances to aid in the immune response, but the release of excessive amounts of these substances causes damage to one or more organs, most commonly the heart, skin, lungs, or nervous system. Eosinophil-associated organ damage can lead to a heart condition known as eosinophilic endomyocardial disease, skin rashes, coughing, difficulty breathing, swelling (edema) in the lower limbs, confusion, changes in behavior, or impaired movement or sensations. People with PDGFRA-associated chronic eosinophilic leukemia can also have an enlarged spleen (splenomegaly) and elevated levels of certain chemicals called vitamin B12 and tryptase in the blood. Some people with PDGFRA-associated chronic eosinophilic leukemia have an increased number of other types of white blood cells, such as neutrophils or mast cells. Occasionally, people with PDGFRA-associated chronic eosinophilic leukemia develop other blood cell cancers, such as acute myeloid leukemia or B-cell or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. PDGFRA-associated chronic eosinophilic leukemia is often grouped with a related condition called hypereosinophilic syndrome. These two conditions have very similar signs and symptoms; however, the cause of hypereosinophilic syndrome is unknown. | PDGFRA-associated chronic eosinophilic leukemia |
How many people are affected by PDGFRA-associated chronic eosinophilic leukemia ? | PDGFRA-associated chronic eosinophilic leukemia is a rare condition; however, the exact prevalence is unknown. | PDGFRA-associated chronic eosinophilic leukemia |
What are the genetic changes related to PDGFRA-associated chronic eosinophilic leukemia ? | PDGFRA-associated chronic eosinophilic leukemia is caused by mutations in the PDGFRA gene. This condition usually occurs as a result of genetic rearrangements that fuse part of the PDGFRA gene with part of another gene. Rarely, changes in single DNA building blocks (point mutations) in the PDGFRA gene are found in people with this condition. Genetic rearrangements and point mutations affecting the PDGFRA gene are somatic mutations, which are mutations acquired during a person's lifetime that are present only in certain cells. The somatic mutation occurs initially in a single cell, which continues to grow and divide, producing a group of cells with the same mutation (a clonal population). The most common genetic abnormality in PDGFRA-associated chronic eosinophilic leukemia results from a deletion of genetic material from chromosome 4, which brings together part of the PDGFRA gene and part of the FIP1L1 gene, creating the FIP1L1-PDGFRA fusion gene. The FIP1L1 gene provides instructions for a protein that plays a role in forming the genetic blueprints for making proteins (messenger RNA or mRNA). The PDGFRA gene provides instructions for making a receptor protein that is found in the cell membrane of certain cell types. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. When the ligand attaches (binds), the PDGFRA receptor protein is turned on (activated), which leads to activation of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, such as cell growth and division (proliferation) and cell survival. The FIP1L1-PDGFRA fusion gene (as well as other PDGFRA fusion genes) provides instructions for making a fusion protein that has the function of the normal PDGFRA protein. However, the fusion protein does not require ligand binding to be activated. Similarly, point mutations in the PDGFRA gene can result in a PDGFRA protein that is activated without ligand binding. As a result, the signaling pathways are constantly turned on (constitutively activated), which increases the proliferation and survival of cells. When the FIP1L1-PDGFRA fusion gene mutation or point mutations in the PDGFRA gene occur in blood cell precursors, the growth of eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) is poorly controlled, leading to PDGFRA-associated chronic eosinophilic leukemia. It is unclear why eosinophils are preferentially affected by this genetic change. | PDGFRA-associated chronic eosinophilic leukemia |
Is PDGFRA-associated chronic eosinophilic leukemia inherited ? | PDGFRA-associated chronic eosinophilic leukemia is not inherited and occurs in people with no history of the condition in their families. Mutations that lead to a PDGFRA fusion gene and PDGFRA point mutations are somatic mutations, which means they occur during a person's lifetime and are found only in certain cells. Somatic mutations are not inherited. Males are more likely to develop PDGFRA-associated chronic eosinophilic leukemia than females because, for unknown reasons, PDGFRA fusion genes are found more often in males. | PDGFRA-associated chronic eosinophilic leukemia |
What are the treatments for PDGFRA-associated chronic eosinophilic leukemia ? | These resources address the diagnosis or management of PDGFRA-associated chronic eosinophilic leukemia: - Cancer.Net: Leukemia - Eosinophilic: Treatment - Genetic Testing Registry: Idiopathic hypereosinophilic syndrome - MedlinePlus Encyclopedia: Eosinophil Count - Absolute - Seattle Cancer Care Alliance: Hypereosinophilia 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 | PDGFRA-associated chronic eosinophilic leukemia |
What is (are) mitochondrial complex III deficiency ? | Mitochondrial complex III deficiency is a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and the muscles used for movement (skeletal muscles). Signs and symptoms of mitochondrial complex III deficiency usually begin in infancy but can appear later. The severity of mitochondrial complex III deficiency varies widely among affected individuals. People who are mildly affected tend to have muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). More severely affected individuals have problems with multiple body systems, such as liver disease that can lead to liver failure, kidney abnormalities (tubulopathy), and brain dysfunction (encephalopathy). Encephalopathy can cause delayed development of mental and motor skills (psychomotor delay), movement problems, weak muscle tone (hypotonia), and difficulty with communication. Some affected individuals have a form of heart disease called cardiomyopathy, which can lead to heart failure. Most people with mitochondrial complex III deficiency have a buildup of a chemical called lactic acid in the body (lactic acidosis). Some affected individuals also have buildup of molecules called ketones (ketoacidosis) or high blood sugar levels (hyperglycemia). Abnormally high levels of these chemicals in the body can be life-threatening. Mitochondrial complex III deficiency can be fatal in childhood, although individuals with mild signs and symptoms can survive into adolescence or adulthood. | mitochondrial complex III deficiency |
How many people are affected by mitochondrial complex III deficiency ? | The prevalence of mitochondrial complex III deficiency is unknown, although the condition is thought to be rare. | mitochondrial complex III deficiency |
What are the genetic changes related to mitochondrial complex III deficiency ? | Mitochondrial complex III deficiency can be caused by mutations in one of several genes. The proteins produced from these genes either are a part of or help assemble a group of proteins called complex III. The two most commonly mutated genes involved in mitochondrial complex III deficiency are MT-CYB and BCS1L. It is likely that genes that have not been identified are also involved in this condition. Cytochrome b, produced from the MT-CYB gene, is one component of complex III, and the protein produced from the BCS1L gene is critical for the formation of the complex. Complex III is found in cell structures called mitochondria, which convert the energy from food into a form that cells can use. Complex III is one of several complexes that carry out a multistep process called oxidative phosphorylation, through which cells derive much of their energy. As a byproduct of its action in oxidative phosphorylation, complex III produces reactive oxygen species, which are harmful molecules that can damage DNA and tissues. MT-CYB and BCS1L gene mutations impair the formation of complex III molecules. As a result, complex III activity and oxidative phosphorylation are reduced. Researchers believe that impaired oxidative phosphorylation can lead to cell death by reducing the amount of energy available in the cell. It is thought that tissues and organs that require a lot of energy, such as the brain, liver, kidneys, and skeletal muscles, are most affected by a reduction in oxidative phosphorylation. In addition, for unknown reasons, BCS1L gene mutations lead to increased overall production of reactive oxygen species, although production by complex III is reduced. Damage from reduced energy and from reactive oxygen species likely contributes to the signs and symptoms of mitochondrial complex III deficiency. Unlike most genes, the MT-CYB gene is found in DNA located in mitochondria, called mitochondrial DNA (mtDNA). This location may help explain why some people have more severe features of the condition than others. Most of the body's cells contain thousands of mitochondria, each with one or more copies of mtDNA. These cells can have a mix of mitochondria containing mutated and unmutated DNA (heteroplasmy). When caused by MT-CYB gene mutations, the severity of mitochondrial complex III deficiency is thought to be associated with the percentage of mitochondria with the gene mutation. The other genes known to be involved in this condition are found in DNA packaged in chromosomes within the cell nucleus (nuclear DNA). It is not clear why the severity of the condition varies in people with mutations in these other genes. | mitochondrial complex III deficiency |
Is mitochondrial complex III deficiency inherited ? | Mitochondrial complex III deficiency is usually 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. In some cases caused by mutations in the MT-CYB gene, the condition is not inherited; it is caused by new mutations in the gene that occur in people with no history of the condition in their family. Other cases caused by mutations in the MT-CYB gene are inherited in a mitochondrial pattern, which is also known as maternal inheritance. This pattern of inheritance applies to genes contained in mtDNA. Because egg cells, but not sperm cells, contribute mitochondria to the developing embryo, children can only inherit disorders resulting from mtDNA mutations from their mother. These disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass traits associated with changes in mtDNA to their children. | mitochondrial complex III deficiency |
What are the treatments for mitochondrial complex III deficiency ? | These resources address the diagnosis or management of mitochondrial complex III deficiency: - Gene Review: Gene Review: Mitochondrial Disorders Overview - Genetic Testing Registry: MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 6 - Genetic Testing Registry: MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 7 - Genetic Testing Registry: MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 8 - Genetic Testing Registry: Mitochondrial complex III deficiency - Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 2 - Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 3 - Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 4 - Genetic Testing Registry: Mitochondrial complex III deficiency, nuclear type 5 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 | mitochondrial complex III deficiency |
What is (are) primary myelofibrosis ? | Primary myelofibrosis is a condition characterized by the buildup of scar tissue (fibrosis) in the bone marrow, the tissue that produces blood cells. Because of the fibrosis, the bone marrow is unable to make enough normal blood cells. The shortage of blood cells causes many of the signs and symptoms of primary myelofibrosis. Initially, most people with primary myelofibrosis have no signs or symptoms. Eventually, fibrosis can lead to a reduction in the number of red blood cells, white blood cells, and platelets. A shortage of red blood cells (anemia) often causes extreme tiredness (fatigue) or shortness of breath. A loss of white blood cells can lead to an increased number of infections, and a reduction of platelets can cause easy bleeding or bruising. Because blood cell formation (hematopoiesis) in the bone marrow is disrupted, other organs such as the spleen or liver may begin to produce blood cells. This process, called extramedullary hematopoiesis, often leads to an enlarged spleen (splenomegaly) or an enlarged liver (hepatomegaly). People with splenomegaly may feel pain or fullness in the abdomen, especially below the ribs on the left side. Other common signs and symptoms of primary myelofibrosis include fever, night sweats, and bone pain. Primary myelofibrosis is most commonly diagnosed in people aged 50 to 80 but can occur at any age. | primary myelofibrosis |
How many people are affected by primary myelofibrosis ? | Primary myelofibrosis is a rare condition that affects approximately 1 in 500,000 people worldwide. | primary myelofibrosis |
What are the genetic changes related to primary myelofibrosis ? | Mutations in the JAK2, MPL, CALR, and TET2 genes are associated with most cases of primary myelofibrosis. The JAK2 and MPL genes provide instructions for making proteins that promote the growth and division (proliferation) of blood cells. The CALR gene provides instructions for making a protein with multiple functions, including ensuring the proper folding of newly formed proteins and maintaining the correct levels of stored calcium in cells. The TET2 gene provides instructions for making a protein whose function is unknown. The proteins produced from the JAK2 and MPL genes are both part of a signaling pathway called the JAK/STAT pathway, which transmits chemical signals from outside the cell to the cell's nucleus. The protein produced from the MPL gene, called thrombopoietin receptor, turns on (activates) the pathway, and the JAK2 protein transmits signals after activation. Through the JAK/STAT pathway, these two proteins promote the proliferation of blood cells, particularly a type of blood cell known as a megakaryocyte. Mutations in either the JAK2 gene or the MPL gene that are associated with primary myelofibrosis lead to overactivation of the JAK/STAT pathway. The abnormal activation of JAK/STAT signaling leads to overproduction of abnormal megakaryocytes, and these megakaryocytes stimulate another type of cell to release collagen. Collagen is a protein that normally provides structural support for the cells in the bone marrow. However, in primary myelofibrosis, the excess collagen forms scar tissue in the bone marrow. Although mutations in the CALR gene and the TET2 gene are relatively common in primary myelofibrosis, it is unclear how these mutations are involved in the development of the condition. Some people with primary myelofibrosis do not have a mutation in any of the known genes associated with this condition. Researchers are working to identify other genes that may be involved in the condition. | primary myelofibrosis |
Is primary myelofibrosis inherited ? | This condition is generally not inherited but arises from gene mutations that occur in early blood-forming cells after conception. These alterations are called somatic mutations. | primary myelofibrosis |
What are the treatments for primary myelofibrosis ? | These resources address the diagnosis or management of primary myelofibrosis: - Genetic Testing Registry: Myelofibrosis - Merck Manual Professional Version: Primary Myelofibrosis - Myeloproliferative Neoplasm (MPN) Research Foundation: Primary Myelofibrosis (PMF) 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 | primary myelofibrosis |
What is (are) Freeman-Sheldon syndrome ? | Freeman-Sheldon syndrome is a condition that primarily affects the face, hands, and feet. People with this disorder have a distinctive facial appearance including a small mouth (microstomia) with pursed lips, giving the appearance of a "whistling face." For this reason, the condition is sometimes called "whistling face syndrome." People with Freeman-Sheldon syndrome may also have a prominent forehead and brow ridges, a sunken appearance of the middle of the face (midface hypoplasia), a short nose, a long area between the nose and mouth (philtrum), deep folds in the skin between the nose and lips (nasolabial folds), full cheeks, and a chin dimple shaped like an "H" or "V". Affected individuals may have a number of abnormalities that affect the eyes. These may include widely spaced eyes (hypertelorism), deep-set eyes, outside corners of the eyes that point downward (down-slanting palpebral fissures), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), and eyes that do not look in the same direction (strabismus). Other facial features that may occur in Freeman-Sheldon syndrome include an unusually small tongue (microglossia) and jaw (micrognathia) and a high arch in the roof of the mouth (high-arched palate). People with this disorder may have difficulty swallowing (dysphagia), a failure to gain weight and grow at the expected rate (failure to thrive), and respiratory complications that may be life-threatening. Speech problems are also common in this disorder. Some affected individuals have hearing loss. Freeman-Sheldon syndrome is also characterized by joint deformities (contractures) that restrict movement. People with this disorder typically have multiple contractures in the hands and feet at birth (distal arthrogryposis). These contractures lead to permanently bent fingers and toes (camptodactyly), a hand deformity in which all of the fingers are angled outward toward the fifth finger (ulnar deviation, also called "windmill vane hand"), and inward- and downward-turning feet (clubfoot). Affected individuals may also have a spine that curves to the side (scoliosis). People with Freeman-Sheldon syndrome also have an increased risk of developing a severe reaction to certain drugs used during surgery and other invasive procedures. This reaction is called malignant hyperthermia. Malignant hyperthermia occurs in response to some anesthetic gases, which are used to block the sensation of pain. A particular type of muscle relaxant may also trigger the reaction. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. The complications of malignant hyperthermia can be life-threatening unless they are treated promptly. Intelligence is unaffected in most people with Freeman-Sheldon syndrome, but approximately one-third have some degree of intellectual disability. | Freeman-Sheldon syndrome |
How many people are affected by Freeman-Sheldon syndrome ? | Freeman-Sheldon syndrome is a rare disorder; its exact prevalence is unknown. | Freeman-Sheldon syndrome |
What are the genetic changes related to Freeman-Sheldon syndrome ? | Freeman-Sheldon syndrome may be caused by mutations in the MYH3 gene. The MYH3 gene provides instructions for making a protein called embryonic skeletal muscle myosin heavy chain 3. This protein belongs to a group of proteins called myosins, which are involved in cell movement and transport of materials within and between cells. Myosin and another protein called actin are the primary components of muscle fibers and are important for the tensing of muscles (muscle contraction). Embryonic skeletal muscle myosin heavy chain 3 forms part of a myosin protein complex that is active before birth and is important for normal development of the muscles. MYH3 gene mutations that cause Freeman-Sheldon syndrome likely disrupt the function of the embryonic skeletal muscle myosin heavy chain 3 protein, reducing the ability of fetal muscle cells to contract. This impairment of muscle contraction may interfere with muscle development in the fetus, resulting in the contractures and other muscle and skeletal abnormalities associated with Freeman-Sheldon syndrome. It is unclear how MYH3 gene mutations may cause other features of this disorder. Some people with Freeman-Sheldon syndrome do not have mutations in the MYH3 gene. In these individuals, the cause of the disorder is unknown. | Freeman-Sheldon syndrome |
Is Freeman-Sheldon syndrome inherited ? | Freeman-Sheldon syndrome can have different inheritance patterns. In some cases, the 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. The condition can also have an autosomal recessive inheritance 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. In some cases, the inheritance pattern is unknown. | Freeman-Sheldon syndrome |
What are the treatments for Freeman-Sheldon syndrome ? | These resources address the diagnosis or management of Freeman-Sheldon syndrome: - Genetic Testing Registry: Freeman-Sheldon 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 | Freeman-Sheldon syndrome |
What is (are) Opitz G/BBB syndrome ? | Opitz G/BBB syndrome is a genetic condition that causes several abnormalities along the midline of the body. "G/BBB" represents the first letters of the last names of the families first diagnosed with this disorder and "Opitz" is the last name of the doctor who first described the signs and symptoms. There are two forms of Opitz G/BBB syndrome, X-linked Opitz G/BBB syndrome and autosomal dominant Opitz G/BBB syndrome. The two forms are distinguished by their genetic causes and patterns of inheritance. The signs and symptoms of the two forms are generally the same. Nearly everyone with Opitz G/BBB syndrome has wide-spaced eyes (ocular hypertelorism). Affected individuals commonly have defects of the voice box (larynx), windpipe (trachea), or esophagus. These throat abnormalities can cause difficulty swallowing or breathing, in some cases resulting in recurrent pneumonia or life-threatening breathing problems. A common defect is a gap between the trachea and esophagus (laryngeal cleft) that allows food or fluids to enter the airway. The cleft can vary in size, and infants may struggle to breathe when feeding. Most males with Opitz G/BBB syndrome have genital abnormalities such as the urethra opening on the underside of the penis (hypospadias), undescended testes (cryptorchidism), an underdeveloped scrotum, or a scrotum divided into two lobes (bifid scrotum). These genital abnormalities can lead to problems in the urinary tract. Mild intellectual disability and developmental delay occur in about 50 percent of people with Opitz G/BBB syndrome. Affected individuals have delayed motor skills, such as walking, speech delay, and learning difficulties. Some people with Opitz G/BBB syndrome have features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills. About half of affected individuals also have an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate). Some have cleft palate without cleft lip. Less common features of Opitz G/BBB syndrome, affecting less than half of people with this disorder, include minor heart defects, an obstruction of the anal opening (imperforate anus), and brain defects such as a small or absent connection between the left and right halves of the brain (corpus callosum). Distinct facial features that may be seen in this disorder include a prominent forehead, widow's peak hairline, flat nasal bridge, thin upper lip, and low-set ears. These features vary among affected individuals, even within the same family. | Opitz G/BBB syndrome |
How many people are affected by Opitz G/BBB syndrome ? | X-linked Opitz G/BBB syndrome is thought to affect 1 in 10,000 to 50,000 males, although it is likely that this condition is underdiagnosed. The incidence of autosomal dominant Opitz G/BBB syndrome is unknown. It is part of a larger condition known as 22q11.2 deletion syndrome, which is estimated to affect 1 in 4,000 people. | Opitz G/BBB syndrome |
What are the genetic changes related to Opitz G/BBB syndrome ? | X-linked Opitz G/BBB syndrome is caused by mutations in the MID1 gene. The MID1 gene provides instructions for making a protein called midline-1. This protein attaches (binds) to microtubules, which are rigid, hollow fibers that make up the cell's structural framework (the cytoskeleton). Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the movement of cells (cell migration). Midline-1 assists in recycling certain proteins that need to be reused instead of broken down. MID1 gene mutations lead to a decrease in midline-1 function, which prevents protein recycling. The resulting accumulation of proteins impairs microtubule function, leading to problems with cell division and migration. It is unclear how these changes disrupt normal development and cause the signs and symptoms of Opitz G/BBB syndrome. Autosomal dominant Opitz G/BBB syndrome is caused by changes in chromosome 22. Some affected individuals have a deletion of a small piece of chromosome 22, specifically at an area of the chromosome designated 22q11.2. Because this same region is deleted in another condition called 22q11.2 deletion syndrome, researchers often consider Opitz/GBBB syndrome caused by this genetic change to be a form of 22q11.2 deletion syndrome. It is not known which of the deleted genes contribute to the signs and symptoms of Opitz G/BBB syndrome. In other people, autosomal dominant Opitz/GBBB syndrome is caused by a mutation in the SPECC1L gene, which is near the 22q11.2 region but is not in the area that is typically deleted in other individuals with autosomal dominant Opitz G/BBB syndrome or 22q11.2 deletion syndrome. The SPECC1L gene provides instructions for making a protein called cytospin-A. This protein interacts with components of the cytoskeleton and stabilizes microtubules, which is necessary for these fibers to regulate various cell processes including the movement of cells to their proper location (cell migration). Cytospin-A is particularly involved in the migration of cells that will form the facial features. Mutations in the SPECC1L gene result in the production of a protein with a decreased ability to interact with components of the cytoskeleton. As a result, microtubules are disorganized and cells have trouble migrating to their proper location. Because the SPECC1L gene plays a role in facial development, mutations in this gene likely account for the cleft lip and palate seen in some individuals with Opitz G/BBB syndrome, but it is unclear how SPECC1L gene mutations cause the other features of this disorder. Some people with Opitz G/BBB syndrome do not have any of the genetic changes described above. The cause of the condition in these individuals is unknown. | Opitz G/BBB syndrome |
Is Opitz G/BBB syndrome inherited ? | When caused by mutations in the MID1 gene, Opitz G/BBB syndrome has an X-linked pattern of inheritance. It is considered X-linked because the MID1 gene is located on the X chromosome, one of the two sex chromosomes in each cell. In males, who have only one X chromosome, a mutation in the only copy of the gene in each cell is sufficient to cause the condition. In females, who have two copies of the X chromosome, one altered copy of the gene in each cell can lead to less severe features of the condition or may cause no symptoms at all. Because it is unlikely that females will have two altered copies of the MID1 gene, females with X-linked Opitz G/BBB syndrome typically have hypertelorism as the only sign of the disorder. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Rarely, Opitz G/BBB syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. These cases are caused by a mutation in the SPECC1L gene or by a deletion of genetic material from one copy of chromosome 22 in each cell. Males and females with autosomal dominant Opitz G/BBB syndrome usually have the same severity of symptoms. In both types of Opitz G/BBB syndrome, some affected people inherit the genetic change from an affected parent. Other cases may result from new mutations. These cases occur in people with no history of the disorder in their family. | Opitz G/BBB syndrome |
What are the treatments for Opitz G/BBB syndrome ? | These resources address the diagnosis or management of Opitz G/BBB syndrome: - Gene Review: Gene Review: 22q11.2 Deletion Syndrome - Gene Review: Gene Review: X-Linked Opitz G/BBB Syndrome - Genetic Testing Registry: Opitz G/BBB syndrome - Genetic Testing Registry: Opitz-Frias syndrome - MedlinePlus Encyclopedia: Hypospadias - MedlinePlus Encyclopedia: Imperforate Anus 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 | Opitz G/BBB syndrome |
What is (are) alpha thalassemia X-linked intellectual disability syndrome ? | Alpha thalassemia X-linked intellectual disability syndrome is an inherited disorder that affects many parts of the body. This condition occurs almost exclusively in males. Males with alpha thalassemia X-linked intellectual disability syndrome have intellectual disability and delayed development. Their speech is significantly delayed, and most never speak or sign more than a few words. Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with this disorder are never able to walk independently. Almost everyone with alpha thalassemia X-linked intellectual disability syndrome has distinctive facial features, including widely spaced eyes, a small nose with upturned nostrils, and low-set ears. The upper lip is shaped like an upside-down "V," and the lower lip tends to be prominent. These facial characteristics are most apparent in early childhood. Over time, the facial features become coarser, including a flatter face with a shortened nose. Most affected individuals have mild signs of a blood disorder called alpha thalassemia. This disorder reduces the production of hemoglobin, which is the protein in red blood cells that carries oxygen to cells throughout the body. A reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Rarely, affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, and fatigue. Additional features of alpha thalassemia X-linked intellectual disability syndrome include an unusually small head size (microcephaly), short stature, and skeletal abnormalities. Many affected individuals have problems with the digestive system, such as a backflow of stomach acids into the esophagus (gastroesophageal reflux) and chronic constipation. Genital abnormalities are also common; affected males may have undescended testes and the opening of the urethra on the underside of the penis (hypospadias). In more severe cases, the external genitalia do not look clearly male or female (ambiguous genitalia). | alpha thalassemia X-linked intellectual disability syndrome |
How many people are affected by alpha thalassemia X-linked intellectual disability syndrome ? | Alpha thalassemia X-linked intellectual disability syndrome appears to be a rare condition, although its exact prevalence is unknown. More than 200 affected individuals have been reported. | alpha thalassemia X-linked intellectual disability syndrome |
What are the genetic changes related to alpha thalassemia X-linked intellectual disability syndrome ? | Alpha thalassemia X-linked intellectual disability syndrome results from mutations in the ATRX gene. This gene provides instructions for making a protein that plays an essential role in normal development. Although the exact function of the ATRX protein is unknown, studies suggest that it helps regulate the activity (expression) of other genes. Among these genes are HBA1 and HBA2, which are necessary for normal hemoglobin production. Mutations in the ATRX gene change the structure of the ATRX protein, which likely prevents it from effectively regulating gene expression. Reduced activity of the HBA1 and HBA2 genes causes alpha thalassemia. Abnormal expression of other genes, which have not been identified, probably causes developmental delay, distinctive facial features, and the other signs and symptoms of alpha thalassemia X-linked intellectual disability syndrome. | alpha thalassemia X-linked intellectual disability syndrome |
Is alpha thalassemia X-linked intellectual disability syndrome inherited ? | This condition is inherited in an X-linked recessive pattern. The ATRX gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), one working copy of the ATRX gene can usually compensate for the mutated copy. Therefore, females who carry a single mutated ATRX gene almost never have signs of alpha thalassemia X-linked intellectual disability syndrome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. | alpha thalassemia X-linked intellectual disability syndrome |
What are the treatments for alpha thalassemia X-linked intellectual disability syndrome ? | These resources address the diagnosis or management of alpha thalassemia X-linked intellectual disability syndrome: - Gene Review: Gene Review: Alpha-Thalassemia X-Linked Intellectual Disability Syndrome - Genetic Testing Registry: ATR-X syndrome - MedlinePlus Encyclopedia: Ambiguous Genitalia - MedlinePlus Encyclopedia: Hypospadias 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 | alpha thalassemia X-linked intellectual disability syndrome |
What is (are) nephrogenic diabetes insipidus ? | Nephrogenic diabetes insipidus is a disorder of water balance. The body normally balances fluid intake with the excretion of fluid in urine. However, people with nephrogenic diabetes insipidus produce too much urine (polyuria), which causes them to be excessively thirsty (polydipsia). Affected individuals can quickly become dehydrated if they do not drink enough water, especially in hot weather or when they are sick. Nephrogenic diabetes insipidus can be either acquired or hereditary. The acquired form is brought on by certain drugs and chronic diseases and can occur at any time during life. The hereditary form is caused by genetic mutations, and its signs and symptoms usually become apparent within the first few months of life. Infants with hereditary nephrogenic diabetes insipidus may eat poorly and fail to gain weight and grow at the expected rate (failure to thrive). They may also be irritable and experience fevers, diarrhea, and vomiting. Recurrent episodes of dehydration can lead to slow growth and delayed development. If the condition is not well-managed, over time it can damage the bladder and kidneys leading to pain, infections, and kidney failure. With appropriate treatment, affected individuals usually have few complications and a normal lifespan. Nephrogenic diabetes insipidus should not be confused with diabetes mellitus, which is much more common. Diabetes mellitus is characterized by high blood sugar levels resulting from a shortage of the hormone insulin or an insensitivity to this hormone. Although nephrogenic diabetes insipidus and diabetes mellitus have some features in common, they are separate disorders with different causes. | nephrogenic diabetes insipidus |
How many people are affected by nephrogenic diabetes insipidus ? | The prevalence of nephrogenic diabetes insipidus is unknown, although the condition is thought to be rare. The acquired form occurs more frequently than the hereditary form. | nephrogenic diabetes insipidus |
What are the genetic changes related to nephrogenic diabetes insipidus ? | The hereditary form of nephrogenic diabetes insipidus can be caused by mutations in at least two genes. About 90 percent of all cases of hereditary nephrogenic diabetes insipidus result from mutations in the AVPR2 gene. Most of the remaining 10 percent of cases are caused by mutations in the AQP2 gene. Both of these genes provide instructions for making proteins that help determine how much water is excreted in urine. The acquired form of nephrogenic diabetes insipidus can result from chronic kidney disease, certain medications (such as lithium), low levels of potassium in the blood (hypokalemia), high levels of calcium in the blood (hypercalcemia), or an obstruction of the urinary tract. The kidneys filter the blood to remove waste and excess fluid, which are stored in the bladder as urine. The balance between fluid intake and urine excretion is controlled by a hormone called vasopressin or antidiuretic hormone (ADH). ADH directs the kidneys to concentrate urine by reabsorbing some of the water into the bloodstream. Normally, when a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), increased levels of ADH in the blood tell the kidneys to make less urine. When fluid intake is adequate, lower levels of ADH tell the kidneys to make more urine. Mutations in the AVPR2 or AQP2 genes prevent the kidneys from responding to signals from ADH. Chronic kidney disease, certain drugs, and other factors can also impair the kidneys' ability to respond to this hormone. As a result, the kidneys do not reabsorb water as they should, and the body makes excessive amounts of urine. These problems with water balance are characteristic of nephrogenic diabetes insipidus. | nephrogenic diabetes insipidus |
Is nephrogenic diabetes insipidus inherited ? | When nephrogenic diabetes insipidus results from mutations in the AVPR2 gene, the condition has an X-linked recessive pattern of inheritance. The AVPR2 gene is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation usually has to occur in both copies of the gene to cause the disorder. However, some females who carry a single mutated copy of the AVPR2 gene have features of nephrogenic diabetes insipidus, including polyuria and polydipsia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. When nephrogenic diabetes insipidus is caused by mutations in the AQP2 gene, it can have either an autosomal recessive or, less commonly, an autosomal dominant pattern of inheritance. In autosomal recessive inheritance, 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. In autosomal dominant inheritance, one mutated copy of the AQP2 gene in each cell is sufficient to cause the disorder. | nephrogenic diabetes insipidus |
What are the treatments for nephrogenic diabetes insipidus ? | These resources address the diagnosis or management of nephrogenic diabetes insipidus: - Gene Review: Gene Review: Nephrogenic Diabetes Insipidus - Genetic Testing Registry: Nephrogenic diabetes insipidus - Genetic Testing Registry: Nephrogenic diabetes insipidus, X-linked - Genetic Testing Registry: Nephrogenic diabetes insipidus, autosomal - MedlinePlus Encyclopedia: ADH - MedlinePlus Encyclopedia: Diabetes Insipidus - Nephrogenic 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 | nephrogenic diabetes insipidus |
What is (are) 1p36 deletion syndrome ? | 1p36 deletion syndrome is a disorder that typically causes severe intellectual disability. Most affected individuals do not speak, or speak only a few words. They may have temper tantrums, bite themselves, or exhibit other behavior problems. Most have structural abnormalities of the brain, and seizures occur in more than half of individuals with this disorder. Affected individuals usually have weak muscle tone (hypotonia) and swallowing difficulties (dysphagia). People with 1p36 deletion syndrome have a small head that is also unusually short and wide in proportion to its size (microbrachycephaly). Affected individuals also have distinctive facial features including deep-set eyes with straight eyebrows; a sunken appearance of the middle of the face (midface hypoplasia); a broad, flat nose; a long area between the nose and mouth (philtrum); a pointed chin; and ears that are low-set, rotated backwards, and abnormally shaped. People with 1p36 deletion syndrome may have vision or hearing problems. Some have abnormalities of the skeleton, heart, gastrointestinal system, kidneys, or genitalia. | 1p36 deletion syndrome |
How many people are affected by 1p36 deletion syndrome ? | 1p36 deletion syndrome is believed to affect between 1 in 5,000 and 1 in 10,000 newborns. However, this may be an underestimate because some affected individuals are likely never diagnosed. | 1p36 deletion syndrome |
What are the genetic changes related to 1p36 deletion syndrome ? | 1p36 deletion syndrome is caused by a deletion of genetic material from a specific region in the short (p) arm of chromosome 1. The signs and symptoms of 1p36 deletion syndrome are probably related to the loss of multiple genes in this region. The size of the deletion varies among affected individuals. | 1p36 deletion syndrome |
Is 1p36 deletion syndrome inherited ? | Most cases of 1p36 deletion syndrome are not inherited. They result from a chromosomal deletion that occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early fetal development. Affected people typically have no history of the disorder in their family. About 20 percent of people with 1p36 deletion syndrome inherit the chromosome with a deleted segment from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called a balanced translocation, in which no genetic material is gained or lost. Balanced translocations usually do not cause any health problems; however, they can become unbalanced as they are passed to the next generation. Children who inherit an unbalanced translocation can have a chromosomal rearrangement with extra or missing genetic material. Individuals with 1p36 deletion syndrome who inherit an unbalanced translocation are missing genetic material from the short arm of chromosome 1, which results in birth defects and other health problems characteristic of this disorder. | 1p36 deletion syndrome |
What are the treatments for 1p36 deletion syndrome ? | These resources address the diagnosis or management of 1p36 deletion syndrome: - Gene Review: Gene Review: 1p36 Deletion Syndrome - Genetic Testing Registry: Chromosome 1p36 deletion 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 | 1p36 deletion syndrome |
What is (are) mevalonate kinase deficiency ? | Mevalonate kinase deficiency is a condition characterized by recurrent episodes of fever, which typically begin during infancy. Each episode of fever lasts about 3 to 6 days, and the frequency of the episodes varies among affected individuals. In childhood the fevers seem to be more frequent, occurring as often as 25 times a year, but as the individual gets older the episodes occur less often. Mevalonate kinase deficiency has additional signs and symptoms, and the severity depends on the type of the condition. There are two types of mevalonate kinase deficiency: a less severe type called hyperimmunoglobulinemia D syndrome (HIDS) and a more severe type called mevalonic aciduria (MVA). During episodes of fever, people with HIDS typically have enlargement of the lymph nodes (lymphadenopathy), abdominal pain, joint pain, diarrhea, skin rashes, and headache. Occasionally they will have painful sores called aphthous ulcers around their mouth. In females, these may also occur around the vagina. A small number of people with HIDS have intellectual disability, problems with movement and balance (ataxia), eye problems, and recurrent seizures (epilepsy). Rarely, people with HIDS develop a buildup of protein deposits (amyloidosis) in the kidneys that can lead to kidney failure. Fever episodes in individuals with HIDS can be triggered by vaccinations, surgery, injury, or stress. Most people with HIDS have abnormally high levels of immune system proteins called immunoglobulin D (IgD) and immunoglobulin A (IgA) in the blood. It is unclear why people with HIDS have high levels of IgD and IgA. Elevated levels of these immunoglobulins do not appear to cause any signs or symptoms. Individuals with HIDS do not have any signs and symptoms of the condition between fever episodes and typically have a normal life expectancy. People with MVA have signs and symptoms of the condition at all times, not just during episodes of fever. Affected children have developmental delay, progressive ataxia, progressive problems with vision, and failure to gain weight and grow at the expected rate (failure to thrive). Individuals with MVA typically have an unusually small, elongated head. In childhood or adolescence, affected individuals may develop eye problems such as inflammation of the eye (uveitis), a blue tint in the white part of the eye (blue sclera), an eye disorder called retinitis pigmentosa that causes vision loss, or clouding of the lens of the eye (cataracts). Affected adults may have short stature and may develop muscle weakness (myopathy) later in life. During fever episodes, people with MVA may have an enlarged liver and spleen (hepatosplenomegaly), lymphadenopathy, abdominal pain, diarrhea, and skin rashes. Children with MVA who are severely affected with multiple problems may live only into early childhood; mildly affected individuals may have a normal life expectancy. | mevalonate kinase deficiency |
How many people are affected by mevalonate kinase deficiency ? | More than 200 people with mevalonate kinase deficiency have been reported worldwide; the majority of these individuals have HIDS. | mevalonate kinase deficiency |
What are the genetic changes related to mevalonate kinase deficiency ? | Mutations in the MVK gene cause mevalonate kinase deficiency. The MVK gene provides instructions for making the mevalonate kinase enzyme. This enzyme is involved in the production of cholesterol, which is later converted into steroid hormones and bile acids. Steroid hormones are needed for normal development and reproduction, and bile acids are used to digest fats. Mevalonate kinase also helps to produce other substances that are necessary for certain cellular functions, such as cell growth, cell maturation (differentiation), formation of the cell's structural framework (the cytoskeleton), gene activity (expression), and protein production and modification. Most MVK gene mutations that cause mevalonate kinase deficiency result in an enzyme that is unstable and folded into an incorrect 3-dimensional shape, leading to a reduction of mevalonate kinase enzyme activity. Despite this shortage (deficiency) of mevalonate kinase activity, people with mevalonate kinase deficiency typically have normal production of cholesterol, steroid hormones, and bile acids. It is unclear how a lack of mevalonate kinase activity causes the signs and symptoms of this condition. Some researchers believe the features may be due to a buildup of mevalonic acid, the substance that mevalonate kinase normally acts on. Other researchers think that a shortage of the substances produced from mevalonic acid, such as those substances necessary for certain cellular functions, causes the fever episodes and other features of this condition. The severity of the enzyme deficiency determines the severity of the condition. People who have approximately 1 to 20 percent of normal mevalonate kinase activity typically develop HIDS. Individuals who have less than 1 percent of normal enzyme activity usually develop MVA. | mevalonate kinase deficiency |
Is mevalonate kinase 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. | mevalonate kinase deficiency |
What are the treatments for mevalonate kinase deficiency ? | These resources address the diagnosis or management of mevalonate kinase deficiency: - Genetic Testing Registry: Hyperimmunoglobulin D with periodic fever - Genetic Testing Registry: Mevalonic aciduria 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 | mevalonate kinase deficiency |
What is (are) cystinuria ? | Cystinuria is a condition characterized by the buildup of the amino acid cystine, a building block of most proteins, in the kidneys and bladder. As the kidneys filter blood to create urine, cystine is normally absorbed back into the bloodstream. People with cystinuria cannot properly reabsorb cystine into their bloodstream, so the amino acid accumulates in their urine. As urine becomes more concentrated in the kidneys, the excess cystine forms crystals. Larger crystals become stones that may lodge in the kidneys or in the bladder. Sometimes cystine crystals combine with calcium molecules in the kidneys to form large stones. These crystals and stones can create blockages in the urinary tract and reduce the ability of the kidneys to eliminate waste through urine. The stones also provide sites where bacteria may cause infections. | cystinuria |
How many people are affected by cystinuria ? | Cystinuria affects approximately 1 in 10,000 people. | cystinuria |
What are the genetic changes related to cystinuria ? | Mutations in the SLC3A1 or SLC7A9 gene cause cystinuria. The SLC3A1 and SLC7A9 genes provide instructions for making the two parts (subunits) of a protein complex that is primarily found in the kidneys. Normally this protein complex controls the reabsorption of certain amino acids, including cystine, into the blood from the filtered fluid that will become urine. Mutations in either the SLC3A1 gene or SLC7A9 gene disrupt the ability of the protein complex to reabsorb amino acids, which causes the amino acids to become concentrated in the urine. As the levels of cystine in the urine increase, the crystals typical of cystinuria form. The other amino acids that are reabsorbed by the protein complex do not create crystals when they accumulate in the urine. | cystinuria |
Is cystinuria 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. | cystinuria |
What are the treatments for cystinuria ? | These resources address the diagnosis or management of cystinuria: - Genetic Testing Registry: Cystinuria - MedlinePlus Encyclopedia: Cystinuria - MedlinePlus Encyclopedia: Cystinuria (image) 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 | cystinuria |
What is (are) myostatin-related muscle hypertrophy ? | Myostatin-related muscle hypertrophy is a rare condition characterized by reduced body fat and increased muscle size. Affected individuals have up to twice the usual amount of muscle mass in their bodies. They also tend to have increased muscle strength. Myostatin-related muscle hypertrophy is not known to cause any medical problems, and affected individuals are intellectually normal. | myostatin-related muscle hypertrophy |
How many people are affected by myostatin-related muscle hypertrophy ? | The prevalence of this condition is unknown. | myostatin-related muscle hypertrophy |
What are the genetic changes related to myostatin-related muscle hypertrophy ? | Mutations in the MSTN gene cause myostatin-related muscle hypertrophy. The MSTN gene provides instructions for making a protein called myostatin, which is active in muscles used for movement (skeletal muscles) both before and after birth. This protein normally restrains muscle growth, ensuring that muscles do not grow too large. Mutations that reduce the production of functional myostatin lead to an overgrowth of muscle tissue. | myostatin-related muscle hypertrophy |
Is myostatin-related muscle hypertrophy inherited ? | Myostatin-related muscle hypertrophy has a pattern of inheritance known as incomplete autosomal dominance. People with a mutation in both copies of the MSTN gene in each cell (homozygotes) have significantly increased muscle mass and strength. People with a mutation in one copy of the MSTN gene in each cell (heterozygotes) also have increased muscle bulk, but to a lesser degree. | myostatin-related muscle hypertrophy |
What are the treatments for myostatin-related muscle hypertrophy ? | These resources address the diagnosis or management of myostatin-related muscle hypertrophy: - Gene Review: Gene Review: Myostatin-Related Muscle Hypertrophy - Genetic Testing Registry: Myostatin-related muscle hypertrophy 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 | myostatin-related muscle hypertrophy |
What is (are) small fiber neuropathy ? | Small fiber neuropathy is a condition characterized by severe pain attacks that typically begin in the feet or hands. As a person ages, the pain attacks can affect other regions. Some people initially experience a more generalized, whole-body pain. The attacks usually consist of pain described as stabbing or burning, or abnormal skin sensations such as tingling or itchiness. In some individuals, the pain is more severe during times of rest or at night. The signs and symptoms of small fiber neuropathy usually begin in adolescence to mid-adulthood. Individuals with small fiber neuropathy cannot feel pain that is concentrated in a very small area, such as the prick of a pin. However, they have an increased sensitivity to pain in general (hyperalgesia) and experience pain from stimulation that typically does not cause pain (hypoesthesia). People affected with this condition may also have a reduced ability to differentiate between hot and cold. However, in some individuals, the pain attacks are provoked by cold or warm triggers. Some affected individuals have urinary or bowel problems, episodes of rapid heartbeat (palpitations), dry eyes or mouth, or abnormal sweating. They can also experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain. | small fiber neuropathy |
How many people are affected by small fiber neuropathy ? | The prevalence of small fiber neuropathy is unknown. | small fiber neuropathy |
What are the genetic changes related to small fiber neuropathy ? | Mutations in the SCN9A or SCN10A gene can cause small fiber neuropathy. These genes provide instructions for making pieces (the alpha subunits) of sodium channels. The SCN9A gene instructs the production of the alpha subunit for the NaV1.7 sodium channel and the SCN10A gene instructs the production of the alpha subunit for the NaV1.8 sodium channel. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. The NaV1.7 and NaV1.8 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. The SCN9A gene mutations that cause small fiber neuropathy result in NaV1.7 sodium channels that do not close completely when the channel is turned off. Many SCN10A gene mutations result in NaV1.8 sodium channels that open more easily than usual. The altered channels allow sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, causing individuals to be more sensitive to stimulation that might otherwise not cause pain. In this condition, the small fibers that extend from the nociceptors through which pain signals are transmitted (axons) degenerate over time. The cause of this degeneration is unknown, but it likely accounts for signs and symptoms such as the loss of temperature differentiation and pinprick sensation. The combination of increased pain signaling and degeneration of pain-transmitting fibers leads to a variable condition with signs and symptoms that can change over time. SCN9A gene mutations have been found in approximately 30 percent of individuals with small fiber neuropathy; SCN10A gene mutations are responsible for about 5 percent of cases. In some instances, other health conditions cause this disorder. Diabetes mellitus and impaired glucose tolerance are the most common diseases that lead to this disorder, with 6 to 50 percent of diabetics or pre-diabetics developing small fiber neuropathy. Other causes of this condition include a metabolic disorder called Fabry disease, immune disorders such as celiac disease or Sjogren syndrome, an inflammatory condition called sarcoidosis, and human immunodeficiency virus (HIV) infection. | small fiber neuropathy |
Is small fiber neuropathy inherited ? | Small fiber neuropathy is inherited in an autosomal dominant pattern, which means one copy of the altered SCN9A gene or SCN10A 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 result from new mutations in the gene and occur in people with no history of the disorder in their family. When the genetic cause of small fiber neuropathy is unknown or when the condition is caused by another disorder, the inheritance pattern is unclear. | small fiber neuropathy |
What are the treatments for small fiber neuropathy ? | These resources address the diagnosis or management of small fiber neuropathy: - Genetic Testing Registry: Small fiber neuropathy 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 | small fiber neuropathy |
What is (are) Lynch syndrome ? | Lynch syndrome, often called hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disorder that increases the risk of many types of cancer, particularly cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. People with Lynch syndrome also have an increased risk of cancers of the stomach, small intestine, liver, gallbladder ducts, upper urinary tract, brain, and skin. Additionally, women with this disorder have a high risk of cancer of the ovaries and lining of the uterus (the endometrium). People with Lynch syndrome may occasionally have noncancerous (benign) growths (polyps) in the colon, called colon polyps. In individuals with this disorder, colon polyps occur earlier but not in greater numbers than they do in the general population. | Lynch syndrome |
How many people are affected by Lynch syndrome ? | In the United States, about 140,000 new cases of colorectal cancer are diagnosed each year. Approximately 3 to 5 percent of these cancers are caused by Lynch syndrome. | Lynch syndrome |
What are the genetic changes related to Lynch syndrome ? | Variations in the MLH1, MSH2, MSH6, PMS2, or EPCAM gene increase the risk of developing Lynch syndrome. The MLH1, MSH2, MSH6, and PMS2 genes are involved in the repair of mistakes that occur when DNA is copied in preparation for cell division (a process called DNA replication). Mutations in any of these genes prevent the proper repair of DNA replication mistakes. As the abnormal cells continue to divide, the accumulated mistakes can lead to uncontrolled cell growth and possibly cancer. Mutations in the EPCAM gene also lead to impaired DNA repair, although the gene is not itself involved in this process. The EPCAM gene lies next to the MSH2 gene on chromosome 2; certain EPCAM gene mutations cause the MSH2 gene to be turned off (inactivated), interrupting DNA repair and leading to accumulated DNA mistakes. Although mutations in these genes predispose individuals to cancer, not all people who carry these mutations develop cancerous tumors. | Lynch syndrome |
Is Lynch syndrome inherited ? | Lynch syndrome cancer risk is inherited in an autosomal dominant pattern, which means one inherited copy of the altered gene in each cell is sufficient to increase cancer risk. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer. | Lynch syndrome |
What are the treatments for Lynch syndrome ? | These resources address the diagnosis or management of Lynch syndrome: - American Medical Association and National Coalition for Health Professional Education in Genetics: Understand the Basics of Genetic Testing for Hereditary Colorectal Cancer - Gene Review: Gene Review: Lynch Syndrome - GeneFacts: Lynch Syndrome: Management - Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 3 - Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 4 - Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 5 - Genetic Testing Registry: Hereditary nonpolyposis colorectal cancer type 8 - Genetic Testing Registry: Lynch syndrome - Genetic Testing Registry: Lynch syndrome I - Genetic Testing Registry: Lynch syndrome II - Genomics Education Programme (UK) - MedlinePlus Encyclopedia: Colon Cancer - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes 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 | Lynch syndrome |
What is (are) MECP2 duplication syndrome ? | MECP2 duplication syndrome is a condition that occurs almost exclusively in males and is characterized by moderate to severe intellectual disability. Most people with this condition also have weak muscle tone in infancy, feeding difficulties, poor or absent speech, seizures that may not improve with treatment, or muscle stiffness (spasticity). Individuals with MECP2 duplication syndrome have delayed development of motor skills such as sitting and walking. Some affected individuals experience the loss of previously acquired skills (developmental regression). Approximately one third of people with this condition cannot walk without assistance. Many individuals with MECP2 duplication syndrome have recurrent respiratory tract infections. These respiratory infections are a major cause of death in affected individuals, with almost half succumbing by age 25. | MECP2 duplication syndrome |
How many people are affected by MECP2 duplication syndrome ? | The prevalence of MECP2 duplication syndrome is unknown; approximately 120 affected individuals have been reported in the scientific literature. It is estimated that this condition is responsible for 1 to 2 percent of all cases of intellectual disability caused by changes in the X chromosome. | MECP2 duplication syndrome |
What are the genetic changes related to MECP2 duplication syndrome ? | MECP2 duplication syndrome is caused by a genetic change in which there is an extra copy of the MECP2 gene in each cell. This extra copy of the MECP2 gene is caused by a duplication of genetic material on the long (q) arm of the X chromosome. The size of the duplication varies from 100,000 to 900,000 DNA building blocks (base pairs), also written as 100 to 900 kilobases (kb). The MECP2 gene is always included in this duplication, and other genes may be involved, depending on the size of the duplicated segment. Extra copies of these other genes do not seem to affect the severity of the condition, because people with larger duplications have signs and symptoms that are similar to people with smaller duplications. The MECP2 gene provides instructions for making a protein called MeCP2 that is critical for normal brain function. Researchers believe that this protein has several functions, including regulating other genes in the brain by switching them off when they are not needed. An extra copy of the MECP2 gene leads to the production of excess MeCP2 protein, which is unable to properly regulate the expression of other genes. The misregulation of gene expression in the brain results in abnormal nerve cell (neuronal) function. These neuronal abnormalities cause irregular brain activity, leading to the signs and symptoms of MECP2 duplication syndrome. | MECP2 duplication syndrome |
Is MECP2 duplication syndrome inherited ? | MECP2 duplication syndrome is inherited in an X-linked pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), a duplication of the only copy of the MECP2 gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a duplication of one of the two copies of the gene typically does not cause the disorder. Females usually do not have signs and symptoms of MECP2 duplication syndrome because the X chromosome that contains the duplication may be turned off (inactive) due to a process called X-inactivation. Early in embryonic development in females, one of the two X chromosomes is permanently inactivated in somatic cells (cells other than egg and sperm cells). X-inactivation ensures that females, like males, have only one active copy of the X chromosome in each body cell. Usually X-inactivation occurs randomly, such that each X chromosome is active in about half of the body cells. Sometimes X-inactivation is not random, and one X chromosome is active in more than half of cells. When X-inactivation does not occur randomly, it is called skewed X-inactivation. Research shows that females with an MECP2 gene duplication have skewed X-inactivation, which results in the inactivation of the X chromosome containing the duplication in most cells of the body. This skewed X inactivation ensures that only the chromosome with the normal MECP2 gene is expressed. This skewed X-inactivation is why females with an MECP2 gene duplication typically do not have any features related to the additional genetic material. | MECP2 duplication syndrome |
What are the treatments for MECP2 duplication syndrome ? | These resources address the diagnosis or management of MECP2 duplication syndrome: - Cincinnati Children's Hospital: MECP2-Related Disorders - Cleveland Clinic: Spasticity - Gene Review: Gene Review: MECP2 Duplication Syndrome - Genetic Testing Registry: MECP2 duplication 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 | MECP2 duplication syndrome |
What is (are) aromatase excess syndrome ? | Aromatase excess syndrome is a condition characterized by elevated levels of the female sex hormone estrogen in both males and females. Males with aromatase excess syndrome experience breast enlargement (gynecomastia) in late childhood or adolescence. The bones of affected males grow and develop more quickly and stop growing sooner than usual (advanced bone age). As a result males have an early growth spurt, typically during late childhood, with short stature as an adult. Affected females rarely show signs and symptoms of the condition, but they may have increased breast growth (macromastia), irregular menstrual periods, and short stature. The ability to have children (fertility) is usually normal in both males and females with aromatase excess syndrome. | aromatase excess syndrome |
How many people are affected by aromatase excess syndrome ? | The prevalence of aromatase excess syndrome is unknown; more than 20 cases have been described in the medical literature. | aromatase excess syndrome |
What are the genetic changes related to aromatase excess syndrome ? | Rearrangements of genetic material involving the CYP19A1 gene cause aromatase excess syndrome. The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of estrogen. In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen plays a role in regulating bone growth. The condition can result from several types of genetic rearrangements involving the CYP19A1 gene. These rearrangements alter the activity of the gene and lead to an increase in aromatase production. In affected males, the increased aromatase and subsequent conversion of androgens to estrogen are responsible for the gynecomastia and limited bone growth characteristic of aromatase excess syndrome. Increased estrogen in females can cause symptoms such as irregular menstrual periods and short stature. | aromatase excess syndrome |
Is aromatase excess syndrome inherited ? | This condition is inherited in an autosomal dominant pattern, which means a genetic rearrangement involving one copy of the CYP19A1 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 result from new genetic changes and occur in people with no history of the disorder in their family. | aromatase excess syndrome |
What are the treatments for aromatase excess syndrome ? | These resources address the diagnosis or management of aromatase excess syndrome: - Genetic Testing Registry: Familial gynecomastia, due to increased aromatase activity 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 | aromatase excess syndrome |
What is (are) hereditary fructose intolerance ? | Hereditary fructose intolerance is a condition that affects a person's ability to digest the sugar fructose. Fructose is a simple sugar found primarily in fruits. Affected individuals develop signs and symptoms of the disorder in infancy when fruits, juices, or other foods containing fructose are introduced into the diet. After ingesting fructose, individuals with hereditary fructose intolerance may experience nausea, bloating, abdominal pain, diarrhea, vomiting, and low blood sugar (hypoglycemia). Affected infants may fail to grow and gain weight at the expected rate (failure to thrive). Repeated ingestion of fructose-containing foods can lead to liver and kidney damage. The liver damage can result in a yellowing of the skin and whites of the eyes (jaundice), an enlarged liver (hepatomegaly), and chronic liver disease (cirrhosis). Continued exposure to fructose may result in seizures, coma, and ultimately death from liver and kidney failure. Due to the severity of symptoms experienced when fructose is ingested, most people with hereditary fructose intolerance develop a dislike for fruits, juices, and other foods containing fructose. Hereditary fructose intolerance should not be confused with a condition called fructose malabsorption. In people with fructose malabsorption, the cells of the intestine cannot absorb fructose normally, leading to bloating, diarrhea or constipation, flatulence, and stomach pain. Fructose malabsorption is thought to affect approximately 40 percent of individuals in the Western hemisphere; its cause is unknown. | hereditary fructose intolerance |
How many people are affected by hereditary fructose intolerance ? | The incidence of hereditary fructose intolerance is estimated to be 1 in 20,000 to 30,000 individuals each year worldwide. | hereditary fructose intolerance |
What are the genetic changes related to hereditary fructose intolerance ? | Mutations in the ALDOB gene cause hereditary fructose intolerance. The ALDOB gene provides instructions for making the aldolase B enzyme. This enzyme is found primarily in the liver and is involved in the breakdown (metabolism) of fructose so this sugar can be used as energy. Aldolase B is responsible for the second step in the metabolism of fructose, which breaks down the molecule fructose-1-phosphate into other molecules called glyceraldehyde and dihydroxyacetone phosphate. ALDOB gene mutations reduce the function of the enzyme, impairing its ability to metabolize fructose. A lack of functional aldolase B results in an accumulation of fructose-1-phosphate in liver cells. This buildup is toxic, resulting in the death of liver cells over time. Additionally, the breakdown products of fructose-1-phosphase are needed in the body to produce energy and to maintain blood sugar levels. The combination of decreased cellular energy, low blood sugar, and liver cell death leads to the features of hereditary fructose intolerance. | hereditary fructose intolerance |
Is hereditary fructose intolerance 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. | hereditary fructose intolerance |
What are the treatments for hereditary fructose intolerance ? | These resources address the diagnosis or management of hereditary fructose intolerance: - Boston University: Specifics of Hereditary Fructose Intolerance and Its Diagnosis - Gene Review: Gene Review: Hereditary Fructose Intolerance - Genetic Testing Registry: Hereditary fructosuria - MedlinePlus Encyclopedia: Hereditary Fructose Intolerance 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 | hereditary fructose intolerance |
What is (are) Shwachman-Diamond syndrome ? | Shwachman-Diamond syndrome is an inherited condition that affects many parts of the body, particularly the bone marrow, pancreas, and skeletal system. The major function of bone marrow is to produce new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infection; and platelets, which are necessary for normal blood clotting. In Shwachman-Diamond syndrome, the bone marrow malfunctions and does not make some or all types of white blood cells. A shortage of neutrophils, the most common type of white blood cell, causes a condition called neutropenia. Most people with Shwachman-Diamond syndrome have at least occasional episodes of neutropenia, which makes them more vulnerable to infections such as pneumonia, recurrent ear infections (otitis media), and skin infections. Less commonly, bone marrow abnormalities lead to a shortage of red blood cells (anemia), which causes fatigue and weakness, or a reduction in the amount of platelets (thrombocytopenia), which can result in easy bruising and abnormal bleeding. People with Shwachman-Diamond syndrome 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) and aplastic anemia, which are disorders that affect blood cell production, and a cancer of blood-forming tissue known as acute myeloid leukemia (AML). Shwachman-Diamond syndrome also affects the pancreas, which is an organ that plays an essential role in digestion. One of this organ's main functions is to produce enzymes that help break down and use the nutrients from food. In most infants with Shwachman-Diamond syndrome, the pancreas does not produce enough of these enzymes. This condition is known as pancreatic insufficiency. Infants with pancreatic insufficiency have trouble digesting food and absorbing nutrients that are needed for growth. As a result, they often have fatty, foul-smelling stools (steatorrhea); are slow to grow and gain weight (failure to thrive); and experience malnutrition. Pancreatic insufficiency often improves with age in people with Shwachman-Diamond syndrome. Skeletal abnormalities are another common feature of Shwachman-Diamond syndrome. Many affected individuals have problems with bone formation and growth, most often affecting the hips and knees. Low bone density is also frequently associated with this condition. Some infants are born with a narrow rib cage and short ribs, which can cause life-threatening problems with breathing. The combination of skeletal abnormalities and slow growth results in short stature in most people with this disorder. The complications of this condition can affect several other parts of the body, including the liver, heart, endocrine system (which produces hormones), eyes, teeth, and skin. Additionally, studies suggest that Shwachman-Diamond syndrome may be associated with delayed speech and the delayed development of motor skills such as sitting, standing, and walking. | Shwachman-Diamond syndrome |
How many people are affected by Shwachman-Diamond syndrome ? | Researchers are not sure how common Shwachman-Diamond syndrome is. Several hundred cases have been reported in scientific studies. | Shwachman-Diamond syndrome |
What are the genetic changes related to Shwachman-Diamond syndrome ? | Mutations in the SBDS gene have been identified in about 90 percent of people with the characteristic features of Shwachman-Diamond syndrome. This gene provides instructions for making a protein whose function is unknown, although it is active in cells throughout the body. Researchers suspect that the SBDS protein may play a role in processing RNA (a molecule that is a chemical cousin of DNA). This protein may also be involved in building ribosomes, which are cellular structures that process the cell's genetic instructions to create proteins. It is unclear how SBDS mutations lead to the major signs and symptoms of Shwachman-Diamond syndrome. In cases where no SBDS mutation is found, the cause of this disorder is unknown. | Shwachman-Diamond syndrome |
Is Shwachman-Diamond syndrome 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. | Shwachman-Diamond syndrome |
What are the treatments for Shwachman-Diamond syndrome ? | These resources address the diagnosis or management of Shwachman-Diamond syndrome: - Gene Review: Gene Review: Shwachman-Diamond Syndrome - Genetic Testing Registry: Shwachman syndrome - MedlinePlus Encyclopedia: Malabsorption 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 | Shwachman-Diamond syndrome |
What is (are) Myhre syndrome ? | Myhre syndrome is a condition with features affecting many systems and functions of the body. People with Myhre syndrome usually have delayed development of language and motor skills such as crawling and walking. Most have intellectual disability that ranges from mild to moderate. Some have behavioral issues such as features of autism or related developmental disorders affecting communication and social interaction. People with Myhre syndrome often have hearing loss, which can be caused by changes in the inner ear (sensorineural deafness), changes in the middle ear (conductive hearing loss), or both (mixed hearing loss). Growth is reduced in people with this disorder, beginning before birth and continuing through adolescence. Affected individuals have a low birth weight and are generally shorter than about 97 percent of their peers throughout life. People with Myhre syndrome typically have stiffness of the skin and are usually described as having a muscular appearance. Skeletal abnormalities associated with this disorder include thickening of the skull bones, flattened bones of the spine (platyspondyly), broad ribs, underdevelopment of the winglike structures of the pelvis (hypoplastic iliac wings), and unusually short fingers and toes (brachydactyly). Affected individuals often have joint problems (arthropathy), including stiffness and limited mobility. Typical facial features in people with Myhre syndrome include narrow openings of the eyelids (short palpebral fissures), a shortened distance between the nose and upper lip (a short philtrum), a sunken appearance of the middle of the face (midface hypoplasia), a small mouth with a thin upper lip, and a protruding jaw (prognathism). Some affected individuals also have an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both. Other features that occur in some people with this disorder include constriction of the throat (laryngotracheal stenosis), high blood pressure (hypertension), heart or eye abnormalities, and in males, undescended testes (cryptorchidism). A disorder sometimes called laryngotracheal stenosis, arthropathy, prognathism, and short stature (LAPS) syndrome is now generally considered to be the same condition as Myhre syndrome because it has similar symptoms and the same genetic cause. | Myhre syndrome |
How many people are affected by Myhre syndrome ? | Myhre syndrome is a rare disorder. Only about 30 cases have been documented in the medical literature. For reasons that are unknown, most affected individuals have been males. | Myhre syndrome |
What are the genetic changes related to Myhre syndrome ? | Mutations in the SMAD4 gene cause Myhre syndrome. The SMAD4 gene provides instructions for making a protein involved in transmitting chemical signals from the cell surface to the nucleus. This signaling pathway, called the transforming growth factor beta (TGF-) pathway, allows the environment outside the cell to affect how the cell produces other proteins. As part of this pathway, the SMAD4 protein interacts with other proteins to control the activity of particular genes. These genes influence many areas of development. Some researchers believe that the SMAD4 gene mutations that cause Myhre syndrome impair the ability of the SMAD4 protein to attach (bind) properly with the other proteins involved in the signaling pathway. Other studies have suggested that these mutations result in an abnormally stable SMAD4 protein that remains active in the cell longer. Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome. | Myhre syndrome |
Is Myhre 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. | Myhre syndrome |
What are the treatments for Myhre syndrome ? | These resources address the diagnosis or management of Myhre syndrome: - Centers for Disease Control and Prevention: Types of Hearing Loss - Genetic Testing Registry: Myhre syndrome - National Institute on Deafness and Other Communication Disorders: Communication Considerations for Parents of Deaf and Hard-of-Hearing Children 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 | Myhre syndrome |
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