Congenital hemidysplasia with ichthyosiform erythroderma and limb defects, more commonly known by the acronym CHILD syndrome, is a condition that affects the development of several parts of the body. The signs and symptoms of this disorder are typically limited to either the right side or the left side of the body. ("Hemi-" means "half," and "dysplasia" refers to abnormal growth.) The right side is affected about twice as often as the left side.

People with CHILD syndrome have a skin condition characterized by large patches of skin that are red and inflamed (erythroderma) and covered with flaky scales (ichthyosis). This condition is most likely to occur in skin folds and creases and usually does not affect the face. The skin abnormalities are present at birth and persist throughout life.

CHILD syndrome also disrupts the formation of the arms and legs during early development. Children with this disorder may be born with one or more limbs that are shortened or missing. The limb abnormalities occur on the same side of the body as the skin abnormalities.

Additionally, CHILD syndrome may affect the development of the brain, heart, lungs, and kidneys.

Mutations in the NSDHL gene cause CHILD syndrome. This gene provides instructions for making an enzyme that is involved in the production of cholesterol. Cholesterol is a type of fat that is produced in the body and obtained from foods that come from animals, particularly egg yolks, meat, fish, and dairy products. Although high cholesterol levels are a well-known risk factor for heart disease, the body needs some cholesterol to develop and function normally both before and after birth. Cholesterol is an important component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays a role in the production of certain hormones and digestive acids.

The mutations that underlie CHILD syndrome eliminate the activity of the NSDHL enzyme, which disrupts the normal production of cholesterol within cells. A shortage of this enzyme may also allow potentially toxic byproducts of cholesterol production to build up in the body's tissues. Researchers suspect that low cholesterol levels and/or an accumulation of other substances disrupt the growth and development of many parts of the body. It is not known, however, how a disturbance in cholesterol production leads to the specific features of CHILD syndrome.

Normal Function

The NSDHL gene provides instructions for making an enzyme that is involved in the production (synthesis) of cholesterol. Cholesterol is a lipid (fat) that is obtained from foods that come from animals, particularly egg yolks, meat, fish, and dairy products. The body can also make (synthesize) its own cholesterol. During cholesterol synthesis, the NSDHL enzyme participates in one of several steps that convert a molecule called lanosterol to cholesterol. Specifically, the NSDHL enzyme removes a carbon atom and three hydrogen atoms (a methyl group) in the conversion of lanosterol to cholesterol.

Although high cholesterol levels are a well-known risk factor for heart disease, the body needs some cholesterol to develop and function normally. Before birth, cholesterol interacts with signaling proteins that control early development of the brain, limbs, genital tract, and other structures. It is also an important component of cell membranes and myelin, the fatty covering that insulates nerve cells. Additionally, cholesterol is used to make certain hormones and is important for the production of acids used in digestion (bile acids).

Health Conditions Related to Genetic Changes

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects

At least 18 mutations in the NSDHL gene have been found to cause congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD syndrome). Most of these mutations change single protein building blocks (amino acids) in the NSDHL enzyme. A few other mutations delete part or all of the NSDHL gene. Each of the identified mutations likely prevents the production of any functional NSDHL enzyme, which disrupts the normal synthesis of cholesterol within cells. A shortage of this enzyme may also allow potentially toxic byproducts of cholesterol synthesis to build up in the body's tissues. Researchers suspect that low cholesterol levels and/or an accumulation of other substances disrupts the growth and development of many parts of the body. It is not known, however, how a disturbance in cholesterol synthesis leads to the specific features of CHILD syndrome.

Other Names for This Gene

• H105E3
• NSDHL_HUMAN
• SDR31E1
• Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating
• XAP104

Genomic Location

This condition has an X-linked dominant pattern of inheritance. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. The inheritance is dominant if one copy of the altered gene in each cell is sufficient to cause the condition.

Most cases of CHILD syndrome occur sporadically, which means only one member of a family is affected. Rarely, the condition can run in families and is passed from mother to daughter. Researchers believe that CHILD syndrome occurs almost exclusively in females because affected males die before birth. Only one male with CHILD syndrome has been reported.

CHILD syndrome is a rare disorder; it has been reported in about 60 people worldwide. This condition occurs almost exclusively in females.