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NSDHL gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

NSDHL gene

The NSDHL gene provides instructions for making an enzyme essential for cholesterol synthesis and normal development before birth.

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, and dairy products. The body can also make 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 is part of an enzyme complex that removes a carbon atom and three hydrogen atoms (a methyl group) from lanosterol.

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 the 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 that are used in digestion (bile acids).

Health Conditions Related to Genetic Changes

CHILD syndrome

Several variants (also called mutations) in the NSDHL gene have been found to cause CHILD syndrome, a condition that can affect the development of the arms, legs, and other parts of the body. The signs and symptoms of this disorder are typically limited to only one side of the body.

Most of the variants in the NSDHL gene change single protein building blocks (amino acids) in the NSDHL enzyme. A few other variants delete part or all of the NSDHL gene. Many of these variants prevent 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 can contribute to problems with the growth and development of many parts of the body.

Other Disorders

Variants in the NSDHL gene can cause CK syndrome, a condition characterized by intellectual disabilities and behavior problems in males. Additional symptoms may include:

  • Seizures
  • Small head size (microcephaly)
  • Brain abnormalities

Females who have a variant that causes CK syndrome are typically unaffected; however, some may experience mild behavior problems such as irritability or aggression. CK syndrome is very rare; fewer than 30 people with this condition have been reported in the medical literature.

Other Names for This Gene

  • H105e3
  • NAD(P) dependent steroid dehydrogenase-like
  • SDR31E1
  • XAP104

Frequently Asked Questions

Since most cases of CHILD syndrome are due to somatic mutations that occur after fertilization, the condition is generally not inherited. This means that affected individuals usually do not pass the mutation to their children. However, in rare instances where the mutation is present in the germline (eggs or sperm), there is a potential for inheritance, though this is extremely uncommon. Genetic counseling is recommended to clarify the specific risk based on the family history and the type of mutation.
CHILD syndrome is caused by a mutation in the NSDHL gene that is usually acquired after conception (somatic mutation) rather than inherited. Because the mutation occurs in a specific cluster of cells during early embryonic development, only the tissues derived from that cluster are affected. This results in the characteristic unilateral (one-sided) presentation, where one arm, leg, or side of the face may be underdeveloped or have skin changes while the other side remains normal.
The skin manifestations, which often include ichthyosis (scaly, thickened skin) and hyperpigmentation, can be managed with emollients, keratolytic agents, and sometimes topical retinoids to reduce scaling. While the underlying genetic defect is permanent, the severity of skin symptoms can fluctuate and may improve with age. However, the structural abnormalities, such as limb hypoplasia (underdevelopment), are permanent and may require orthopedic or reconstructive interventions.
The NSDHL enzyme is critical for cholesterol synthesis, and cholesterol is essential for the development of the brain and nervous system. In CHILD syndrome, the deficiency can lead to neurological complications, including intellectual disability, seizures, or motor delays, particularly if the brain tissue on the affected side is involved. The severity of neurological symptoms varies widely among patients and depends on the extent of the cholesterol synthesis disruption in neural tissues.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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