VLDLR Cerebellar Hypoplasia

Excerpt

Clinical characteristics: VLDLR cerebellar hypoplasia (VLDLR-CH) is characterized by non-progressive congenital ataxia that is predominantly truncal and results in delayed ambulation, moderate-to-profound intellectual disability, dysarthria, strabismus, and seizures. Children either learn to walk very late (often after age 6 years) or never achieve independent ambulation. Brain MRI findings include hypoplasia of the inferior portion of the cerebellar vermis and hemispheres, simplified gyration of the cerebral hemispheres, and small brain stem – particularly the pons.

Diagnosis/testing: The diagnosis of VLDLR cerebellar hypoplasia is established in a proband with suggestive clinical and brain MRI findings by identification of biallelic pathogenic variants in VLDLR on molecular genetic testing.

Management: Treatment of manifestations: Seizures and strabismus are treated in the standard manner. Referral to an early intervention program is recommended for access to occupational, physical, and speech therapy, as well as infant mental health services and special educators.

Surveillance: Annual neurologic and rehabilitation evaluations.

Genetic counseling: VLDLR-CH 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. Carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible when the pathogenic variants in a family are known.