WDR62 Primary Microcephaly

Excerpt

Clinical characteristics: In WDR62 primary microcephaly (WDR62-MCPH), microcephaly (occipitofrontal circumference [OFC] ≥2 standard deviations below the mean) is usually present at birth, but in some instances becomes evident later in the first year of life. Growth is otherwise normal. Except for brain malformations in most affected individuals, no other congenital malformations are observed. Central nervous system involvement can include delayed motor development, mild-to-severe intellectual disability (ID), behavior problems, epilepsy, spasticity, and ataxia.

Diagnosis/testing: The diagnosis of WDR62-MCPH is established in a proband with suggestive clinical findings and biallelic pathogenic variants in WDR62 identified by molecular genetic testing.

Management: Treatment of manifestations: Treatment is symptomatic. Care by a multidisciplinary team (often including a pediatric neurologist, developmental pediatrician, speech-language pathologist, occupational and physical therapist, medical geneticist, and social worker) is recommended.

Surveillance: Follow up at each visit to assess: neurologic manifestations and response to medications for those with seizures; developmental progress and educational needs; speech-language development; behavior; physical therapy / occupational therapy needs; and social support.

Genetic counseling: WDR62-MCPH is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a WDR62 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 WDR62 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing, and preimplantation genetic testing are possible.