OMIM ID:
Cerebrotendinous Xanthomatosis
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Juvenile cataracts are the primary ocular feature of this disorder and are found in virtually all patients. These often cause the first symptoms and become evident in the first decade and almost always by the third decade of life. Lens opacification may require extraction at that time and aspirated lens material may contain lipid-containing vacuoles. However, some cataracts may not be diagnosed until the 5th or 6th decades after the onset of neurological symptoms, usually because the opacities are located in the peripheral cortex and do not cause visual symptoms.
Optic atrophy occurs in nearly half of affected individuals. Yellowish flakes resembling cholesterol crystals can sometimes be seen in the vitreous. The fundus may have scattered hard exudates and cholesterol-like deposits along the vascular arcades and arterioles show evidence of atherosclerosis. RPE window defects are common.
Systemic Features
CTX has serious systemic neurologic signs and symptoms resulting from a deficiency of a mitochondrial enzyme, sterol 27-hydroxylase. The result is reduced bile acid synthesis and increased levels of cholestanol in plasma, tissues, and CSF. This results in a characteristic phenotype of tendon xanthomas, and neurological dysfunction including mental regression or illness, cerebellar ataxia, peripheral neuropathy, seizures, and pyramidal signs to various degrees. Neonatal jaundice and diarrhea are common.
Genetics
Inheritance
This autosomal recessive disorder results from a mutation in the CYP27A1 gene (2q33-qter) encoding sterol 27-hydroxylase.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.