ANKRD17-Related Neurodevelopmental Syndrome

Excerpt

Clinical characteristics: ANKRD17-related neurodevelopmental syndrome is characterized by developmental delay – particularly affecting speech – and variable intellectual disability. Additional features include autism spectrum disorder, attention-deficit/hyperactivity disorder, ophthalmologic abnormalities (strabismus and refractive errors), growth deficiency, feeding difficulties, recurrent infections, gait and/or balance disturbances, and epilepsy. Characteristic craniofacial features include triangular face shape, high anterior hairline, deep-set and/or almond-shaped eyes with periorbital fullness, low-set ears, thick nasal alae and flared nostrils, full cheeks, and thin vermilion of the upper lip. Less common but distinctive features include cleft palate with Pierre Robin sequence, renal agenesis, and scoliosis.

Diagnosis/testing: The diagnosis of ANKRD17-related neurodevelopmental syndrome is established in a proband with a heterozygous pathogenic variant in ANKRD17 identified by molecular genetic testing.

Management: Treatment of manifestations: Developmental and educational support; standard treatments for seizures, behavioral findings, ophthalmologic involvement, genitourinary anomalies, and spasticity; feeding therapy with gastrostomy tube placement as needed for persistent feeding issues; routine immunizations; referral to immunologist for those with recurrent infections; family support and care coordination as needed.

Surveillance: Assess developmental progress, educational needs, seizures, changes in tone, movement disorders, growth, nutrition, feeding, and family needs at each visit; assess behavioral and musculoskeletal manifestations annually or as needed.

Pregnancy management: The teratogenic risk to the fetus associated with the use of anti-seizure medication during pregnancy depends on the type of anti-seizure medication used, the dose, and the gestational age of the fetus.

Genetic counseling: ANKRD17-related neurodevelopmental syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant. If the ANKRD17 pathogenic variant identified in the proband is not identified in either parent, the risk to sibs is low but greater than that of the general population because of the possibility of parental germline mosaicism. Once the ANKRD17 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.