TECPR2-Related Hereditary Sensory and Autonomic Neuropathy with Intellectual Disability

Excerpt

Clinical characteristics: TECPR2-related hereditary sensory and autonomic neuropathy with intellectual disability (TECPR2-HSAN with ID) is characterized by developmental delay and subsequent intellectual disability, behavioral abnormalities, neurologic manifestations (muscular hypotonia, sensory neuropathy with lower-limb hypo- or areflexia and ataxic gait), and autonomic dysfunction (including central hypoventilation and apnea, gastrointestinal dysmotility, dysphagia, and gastroesophageal reflux disease with recurrent aspiration). To date, more than 30 individuals with TECPR2-HSAN with ID have been identified.

Diagnosis/testing: The diagnosis of TECPR2-HSAN with ID is established in a proband with suggestive findings and biallelic pathogenic (or likely pathogenic) variants in TECPR2 identified by molecular genetic testing.

Management: Treatment of manifestations: Currently there are no specific disease-modifying treatments for TECPR2-HSAN with ID. Supportive care is recommended to improve quality of life, maximize function, reduce complications, and minimize risk for apnea and asphyxia, the two most common causes of death. Supportive care can include multidisciplinary care by pediatric specialists in neurology, development, behavior, feeding, pulmonology, gastroenterology, orthopedics, ethics, and medical genetics.

Surveillance: Routinely monitor existing manifestations, response to supportive care, and emergence of new manifestations.

Agents/circumstances to avoid: Avoid drugs that cause decreased consciousness, hypopnea, and CO₂ retention such as benzodiazepines or antihistamines; or if necessary, use at low doses with close monitoring.

Genetic counseling: TECPR2-HSAN with ID is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a TECPR2 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 inheriting neither of the familial pathogenic variants. Once the TECPR2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.