Clinical characteristics: SETD1B-related neurodevelopmental disorder (SETD1B-NDD) is characterized by developmental delay (mainly affecting speech and language), intellectual disability, seizures, autism spectrum disorder or autism-like behaviors, and additional behavioral concerns. Speech delay and/or language disorder has been reported in most affected individuals. Delay in gross motor skills and mild-to-moderate intellectual disability are common. Most affected individuals have seizures with variable onset and seizure type. Behavioral issues including hyperactivity, aggression, anxiety, and sleep disorders have been reported in approximately half of individuals. Less common features include ophthalmologic manifestations and feeding issues.
Diagnosis/testing: The diagnosis of SETD1B-NDD is established in a proband with developmental delay / intellectual disability and a heterozygous pathogenic variant in SETD1B identified by molecular genetic testing.
Management: Treatment of manifestations: Developmental support services and educational intervention; standard treatment with anti-seizure medication in those with seizures; early intervention as needed for feeding problems; standard orthopedic management and therapies for spasticity; routine management of ophthalmologic issues and hearing impairment; social work support and care coordination.
Surveillance: At each visit, assessment of growth, feeding, developmental progress, changes in seizures, behavioral issues, sleep issues, musculoskeletal issues, mobility, and need for social work support and care coordination.
Genetic counseling: SETD1B-NDD is an autosomal dominant disorder typically caused by a de novo pathogenic variant. Most individuals diagnosed with SETD1B-NDD have the disorder as the result of a de novo pathogenic variant. Vertical transmission of a SETD1B pathogenic variant from an affected mother to an affected child has been reported in one family. Each child of an individual with SETD1B-NDD has a 50% chance of inheriting the pathogenic variant. Once the SETD1B pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
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