Syndrome

CLINICAL CHARACTERISTICS

syndrome is characterized by mild-to-profound developmental delay, intellectual disability, and hypotonia. Neurobehavioral manifestations (autistic features, agitation/aggression, restlessness, self-harm, tantrums, frustration, overfriendliness, and/or hyperactivity) are also reported. Some individuals have abnormal findings on brain imaging (ventriculomegaly, delayed or lack of myelination, thin or absent corpus callosum, periventricular foci, and/or subcortical white matter abnormalities). Dysmorphic facial features, including depressed nasal bridge, bulbous nose, and hypotonic open mouth, are present in most individuals. Distal limb and/or digit anomalies, ocular manifestations and vision issues, and congenital heart defects have been reported. Other reported features include seizures and/or hearing impairment.

DIAGNOSIS/TESTING: The diagnosis of syndrome is established in a proband with a heterozygous pathogenic variant in identified by molecular genetic testing.

MANAGEMENT

Standardized treatment for developmental, intellectual, and behavioral issues and seizures; treatment of orthopedic manifestations, congenital heart disease, and ocular manifestations per relevant specialist; hearing aids may be helpful per otolaryngologist; community hearing services through early intervention or the school district; treatment of neonatal respiratory issues per intensivist and/or pulmonologist; feeding therapy; gastrostomy tube placement as needed; social work and family support. Monitor developmental progress, educational needs, behavior issues, and development of or changes in seizures at each visit; assessment of mobility and self-help skills at each visit; clinical assessment for scoliosis at each visit with radiographs as needed; assess for changes in visual acuity and strabismus per treating ophthalmologist; audiology evaluation annually or as needed; monitor for evidence of aspiration and/or respiratory insufficiency, nutritional status, safety of oral intake, and family needs at each visit.

GENETIC COUNSELING

syndrome is an autosomal dominant disorder. The majority of probands reported to date whose parents have undergone molecular genetic testing have the disorder as the result of a pathogenic variant that occurred as a event in the proband. Rarely, individuals diagnosed with syndrome have the disorder as the result of a pathogenic variant inherited from a mosaic, apparently unaffected parent. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.