Nicolaides-Baraitser Syndrome

Clinical characteristics: Nicolaides-Baraitser syndrome (NCBRS) is characterized by sparse scalp hair, prominence of the inter-phalangeal joints and distal phalanges due to decreased subcutaneous fat, characteristic coarse facial features, microcephaly, seizures, and developmental delay / intellectual disability. Seizures are of various types and can be difficult to manage. Developmental delay / intellectual disability (ID) is severe in nearly a half, moderate in a third, and mild in the remainder. Nearly a third never develop speech or language skills.

Diagnosis/testing: The diagnosis of NCBRS is established in a proband with suggestive clinical findings and the identification of a heterozygous SMARCA2 pathogenic variant by molecular genetic testing.

Management: Treatment of manifestations: Anti-seizure medication (ASM) for seizures under the care of a neurologist or epileptologist; occupational, physical, and/or speech therapy; routine management of refractive errors and hearing loss.

Surveillance: At least yearly evaluation by a neurologist to assess for and/or manage seizures; yearly evaluation by a developmental pediatrician to assess developmental progress and therapeutic and educational interventions; regular follow up of ophthalmologic and/or audiologic abnormalities.

Genetic counseling: NCBRS is inherited in an autosomal dominant manner. All affected individuals reported to date have NCBRS as the result of a de novo SMARCA2 pathogenic variant. Although no affected sibs have been reported, the risk to sibs is presumed to be greater than in the general population because of the possibility of germline mosaicism in a parent. If the SMARCA2 pathogenic variant has been identified in an affected family member, prenatal testing for pregnancies at theoretic increased risk is possible.