Cerebrotendinous Xanthomatosis

Cerebrotendinous xanthomatosis (CTX) is an inherited lipid storage disorder that causes progressive neurological problems. This is due to the defective enzyme sterol 27-hydroxylase. Infants with CTX may have chronic diarrhea. They will also develop cataracts. Teenagers and young adults with CTX develop nodules on the Achilles tendon and on tendons of the hands, elbows, knees, and neck. These nodules may also occur in the lungs, bones, and brain. The majority of individuals with CTX are intellectually normal until puberty. In adulthood, individuals with CTX develop neurological problems which may include intellectual disability or dementia, seizures, hallucinations, depression, and difficulty coordinating movement and speech. Long-term treatment with chenodeoxycholic acid (CDCA) has shown to stabilize many of the symptoms associated with CTX except for neurologic deficits. CTX is caused by pathogenic variants in the CYP27A1 gene.

CTX is inherited in an autosomal recessive manner. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene for a person to have the genetic disease. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. The child must inherit a pathogenic variant from each carrier parent in order to be affected. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for CTX. However, the risk to have a child affected with CTX is increased. Testing of reproductive partners is recommended for carriers of CTX.

CTX is a rare disorder, estimated to affect 3 to 5 per 100,000 newborns worldwide. CTX is more common in the Moroccan Jewish population, affecting 1 in 108 newborns.

Genetics Home Reference: Cerebrotendinous Xanthomatosis (http://ghr.nlm.nih.gov/)
Genetic Alliance: Cerebrotendinous Xanthomatosis (http://www.diseaseinfosearch.org/)

OMIM [CTX: 213700] (http://www.ncbi.nlm.nih.gov/omim)
Gene Reviews: Cerebrotendinous Xanthomatosis (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

• Full gene sequencing