KPTN-Related Disorder

Excerpt

Clinical characteristics: KPTN-related disorder is characterized by mild-to-profound intellectual disability, global developmental delay, neurobehavioral/psychiatric manifestations (anxiety, stereotypies, hyperactivity, repetitive speech, and impaired social communication), hypotonia, postnatal and progressive macrocephaly, and seizures. Generalized megalencephaly is often present on brain imaging. Some individuals have recurrent infections, conductive hearing impairment, strabismus, nystagmus, ketotic hypoglycemia, thyroid dysfunction, and/or mild skeletal manifestations.

Diagnosis/testing: The diagnosis of KPTN-related disorder is established in a proband with suggestive findings and biallelic pathogenic variants in KPTN identified by molecular genetic testing.

Management: Treatment of manifestations: Developmental and educational support; standard management for behavioral and psychiatric manifestations; standard treatment with anti-seizure medications by an experienced neurologist; pressure-equalizing tubes and/or tonsillectomy and/or adenoidectomy as needed for recurrent upper respiratory tract infections; standard treatment for ophthalmologic involvement; standard treatment for endocrine manifestations; treatment of skeletal manifestations per orthopedist; social work support and care coordination as needed.

Surveillance: At each visit (at least annually), assess developmental progress, educational needs, mobility and self-help skills, head circumference, seizures, balance problems, oral apraxia, frequency and type of infections, musculoskeletal manifestations, and family needs; annual behavioral assessment; annual audiology evaluation; annual assessment for strabismus and vision deficits; assess for hypoglycemia in neonates and then at each visit or with intercurrent illness; educate parents and caregivers on symptoms of hypoglycemia; annual assessment of thyroid function.

Genetic counseling: KPTN-related disorder is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a KPTN pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the KPTN pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.