Neurodevelopmental Disorder

CLINICAL CHARACTERISTICS

neurodevelopmental disorder (-NDD) is associated with developmental delay (DD) / intellectual disability (ID), speech delay, gait or truncal ataxia, hypotonia, behavioral problems, and facial dysmorphism. Variability between individuals with -NDD is significant. Although all affected children have DD noted in early infancy, intellect generally ranges from mild to severe ID, with two individuals functioning in the low normal range. Less common issues can include genitourinary abnormalities and gastrointestinal and/or musculoskeletal involvement. To date, 42 symptomatic individuals from 39 families have been reported.

DIAGNOSIS/TESTING: The diagnosis of -NDD is established in a proband with suggestive findings and a heterozygous pathogenic variant in identified by molecular genetic testing.

MANAGEMENT

Developmental delay / intellectual disability, speech delay, hypotonia and ataxia, behavioral issues, genitourinary abnormalities, gastrointestinal involvement, and musculoskeletal involvement are managed as per standard care. Follow up of manifestations at each clinic visit.

GENETIC COUNSELING

-NDD is an autosomal dominant disorder typically caused by a pathogenic variant. If a parent is known to have the pathogenic variant identified in the proband, the risk to the sibs of inheriting the pathogenic variant is 50%. If the pathogenic variant identified in the proband cannot be detected in the leukocyte DNA of either parent, the recurrence risk to sibs is slightly greater than that of the general population because of the possibility of parental germline mosaicism. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.