Hypomyelination and Congenital Cataract

Abstract

CLINICAL CHARACTERISTICS Hypomyelination and congenital cataract (HCC) is usually characterized by bilateral congenital cataracts and normal psychomotor development in the first year of life, followed by slowly progressive neurologic impairment manifest as ataxia, spasticity (brisk tendon reflexes and bilateral extensor plantar responses), and mild to moderate cognitive impairment. Dysarthria and truncal hypotonia are observed. Cerebellar signs (truncal titubation and intention tremor) and peripheral neuropathy (muscle weakness and wasting of the legs) are present in the majority of affected individuals. Seizures can occur. In a few cases cataracts may be absent. DIAGNOSIS/TESTING HCC can be diagnosed with confidence in individuals with typical clinical findings, characteristic abnormalities on brain MRI, and identifiable pathogenic variants in FAM126A (also known as DRCTNNB1A or HCC). MANAGEMENT Treatment of manifestations: Physical therapy to improve motor function; special education; antiepileptic drugs as needed. Surveillance: Periodic neurologic evaluations to identify neurologic complications; evaluations by a physiatrist to aid with assistive devices as needed; eye examinations if cataracts are not identified in the neonatal period. GENETIC COUNSELING HCC is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Individuals with HCC do not reproduce. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family are known.