Hypomyelination and Congenital Cataract

Excerpt

Clinical characteristics: Hypomyelination and congenital cataract (HCC) is usually characterized by bilateral congenital cataracts and normal psychomotor or only mildly delayed 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. Cataracts may be absent in some individuals.

Diagnosis/testing: The diagnosis of HCC can be established in individuals with typical clinical findings, characteristic abnormalities on brain MRI, and biallelic pathogenic variants in HYCC1 (formerly FAM126A) identified by molecular genetic testing.

Management: Treatment of manifestations: Cataract extraction usually in the first months of life. Therapy support for developmental delays; special education; physical medicine and rehabilitation for spasticity and ataxia. Consider pharmacologic agents for spasticity; anti-seizure medication as needed. Treatment for scoliosis and contractures per orthopedist; feeding therapy and or gastrostomy tube as needed.

Surveillance: Eye examinations if cataracts were not identified in neonatal period. Developmental, neurologic, and musculoskeletal assessments at each visit. Growth measurement, nutrition assessment, and assessment of family need for social work support and care coordination at each visit.

Genetic counseling: HCC is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a HYCC1 pathogenic variant, each sib of an affected individual has at conception 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. Once the HYCC1 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.