Menkes disease (MNK), also known as Menkes syndrome, is an X-linked recessive disorder caused by mutations in genes coding for the copper-transport protein ATP7A, leading to copper deficiency. Characteristic findings include kinky hair, growth failure, and nervous system deterioration. Like all X-linked recessive conditions, Menkes disease is more common in males than in females. The disorder was first described by John Hans Menkes in 1962. Onset occurs during infancy, with incidence of about 1 in 100,000 to 250,000 newborns; affected infants often do not live past the age of three years, though there are rare cases in which less severe symptoms emerge later in childhood. Signs and symptoms Affected infants may be born prematurely. Signs and symptoms appear during infancy, typically after a two- to three-month period of normal or slightly slowed development that is followed by a loss of early developmental skills and subsequent developmental delay. Patients exhibit hypotonia (weak muscle tone), failure to thrive, hypothermia (subnormal body temperature), sagging facial features, seizures, and metaphyseal widening. Hair appears strikingly peculiar: kinky, colorless or silvery, and brittle. There can be extensive neurodegeneration in the gray matter of the brain. Arteries in the brain can also be twisted with frayed and split inner walls. This can lead to rupture or blockage of the arteries. Weakened bones (osteoporosis) may result in fractures. Occipital horn syndrome (sometimes called X-linked cutis laxa or Ehlers-Danlos type 9) is a mild form of Menkes syndrome that begins in early to middle childhood. It is characterized by calcium deposits in a bone at the base of the skull (occipital bone), coarse hair, and loose skin and joints. Cause Mutations in the ATP7A gene, located on chromosome Xq21.1, lead to Menkes syndrome. This condition is inherited in an X-linked recessive pattern. About 30% of MNK cases are due to new mutations and 70% are inherited, almost always from the mother. Even though the disease is more common in males, females can still be a carrier of the disease. As the result of a mutation in the ATP7A gene, copper is poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels and the