Okur-Chung Neurodevelopmental Syndrome

CLINICAL CHARACTERISTICS

Individuals with Okur-Chung neurodevelopmental syndrome (OCNDS) frequently have nonspecific clinical features, delayed language development, motor delay, intellectual disability (typically in the mild-to-moderate range), generalized hypotonia starting in infancy, difficulty feeding, and nonspecific dysmorphic facial features. Developmental delay affects all areas of development, but language is more impaired than gross motor skills in most individuals. Intellectual disability has been reported in about three quarters of individuals. Less common findings may include kyphoscoliosis, postnatal short stature, disrupted circadian rhythm leading to sleep disturbance, seizures, and poor coordination.

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

MANAGEMENT

Feeding therapy and consideration of gastrostomy tube placement in those with persistent feeding issues; consideration of growth hormone therapy (as directed by an endocrinologist) in those with short stature and evidence of partial growth hormone deficiency; standard treatment of epilepsy (as directed by a neurologist) with anti-seizure medication; consideration of intravenous immune globulin treatment (as directed by an immunologist) for demonstrated hypogammaglobulinemia; physical therapy / occupational therapy / rehabilitation medicine for those with hypotonia and/or motor coordination issues; standard supportive developmental therapies; standard treatment of scoliosis, constipation, congenital heart defects, renal anomalies / pelviectasis, and sleep disorders. : At each visit: measure growth parameters, growth velocity, and nutritional status; monitor for signs of ongoing feeding issues / safety of oral intake and constipation; assess new neurologic manifestations (seizures, changes in tone, movement disorders, poor coordination); monitor developmental progress, behavior, and educational needs; monitor for evidence of frequent or unusual infections and for signs and symptoms of sleep disturbance. Every one to three years: ophthalmology evaluation.

GENETIC COUNSELING

OCNDS disorder is expressed in an autosomal dominant manner and typically caused by a pathogenic variant. Therefore, the risk to other family members is presumed to be low. Rarely, individuals diagnosed with OCNDS have the disorder as the result of a pathogenic variant inherited from an affected parent or an unaffected parent with low-level mosaicism in the blood. Once a pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing are possible.