-Related Disorder

CLINICAL CHARACTERISTICS

-related disorder is characterized by moderate-to-profound developmental delay with subsequent intellectual disability, hypotonia, dysmorphic features, seizures, neurobehavioral manifestations (autistic features, sleep issues, stereotypic movements particularly of the hands), vision issues, and cardiac manifestations. Individuals who are able to speak typically only use a few words and are not able to communicate in sentences. Approximately half of individuals are unable to walk independently; however, many are able to walk with some assistance.

DIAGNOSIS/TESTING: The diagnosis of -related disorder is established in a proband by identification of a heterozygous pathogenic variant in by molecular genetic testing.

MANAGEMENT

Developmental and educational services; treatment of gait abnormalities per orthopedist, physical medicine and rehabilitation specialist, and/or physical or occupational therapist; feeding support as needed; standard treatment for gastroesophageal reflux disease, constipation, and seizures; treatment of cardiac manifestations per cardiologist; treatment of refractive errors and strabismus per ophthalmologist; more complex findings or treatment per ophthalmic subspecialist; antibiotics as needed for recurrent respiratory infections and recurrent otitis media; referral to otolaryngologist for tympanostomy tubes as needed for recurrent otitis; family and social work support. At each visit, assess developmental progress, educational needs, gait issues, motor abnormalities, growth parameters, nutritional status, safety of oral intake, gastroesophageal reflux disease, and constipation; assess new or changing seizures, tone, and movement disorders at each visit or per neurologist; annual behavioral assessment; cardiology assessment per cardiologist; ophthalmology evaluation for strabismus and refractive errors per ophthalmologist; assessment for recurrent respiratory infections and/or recurrent otitis media annually or as needed; hearing evaluation in those with recurrent otitis annually or as needed; assess family needs at each visit.

GENETIC COUNSELING

-related disorder is an autosomal dominant disorder. Most probands reported to date with -related disorder whose parents have undergone molecular genetic testing have the disorder as the result of a pathogenic variant. Rarely, a proband diagnosed with -related disorder has the disorder as the result of a pathogenic variant inherited from an affected heterozygous parent or an unaffected mosaic parent. Each child of an individual with -related disorder has a 50% chance of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.