pili torti-developmental delay-neurological abnormalities syndrome

Pili torti-developmental delay-neurological abnormalities syndrome is a multi-system condition characterized by distinctive hair abnormalities, developmental delays, and neurological challenges. The condition has been linked to pathogenic variants in the HEPHL1 gene and is inherited in an autosomal recessive pattern. It has been described in siblings born to consanguineous Puerto Rican parents, highlighting an increased risk when parents share a common ancestor. This condition is very rare, affecting fewer than 1 in one million people.

Individuals with this syndrome exhibit a range of clinical features involving multiple systems. Characteristic findings include pili torti (abnormal twisting of the hair), alongside dermatologic issues such as alopecia, fragile nails, and sparse lateral eyebrows. Neurologically, affected children display poor speech, dysarthria, and aggressive behavior, and they also experience developmental regression. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, with subsequent challenges in communication and behavior. That not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the HEPHL1 gene. HEPHL1 is implicated in the processes that influence hair formation and neurological development, and its disruption leads to the characteristic manifestations of this syndrome. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two mutated copies of the gene, one from each parent. It tends to occur more frequently in families where the parents share a common ancestor, and genetic counseling is recommended to understand the risks for family members.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the individual. Because there are no FDA-approved or foundational therapies available for this condition, a multidisciplinary team is important to address developmental, neurological, and other systemic issues. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients are encouraged to discuss treatment options with their healthcare team and consider genetic counseling to understand the implications for family planning.

The clinical course of pili torti-developmental delay-neurological abnormalities syndrome is highly variable. With current standards of care, outcomes depend on factors such as symptom severity, age at diagnosis, and access to specialized support. Although affected children experience an initial phase of developmental regression, subsequent progression may include periods of relative stabilization with variability in later functional development. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists and genetic counselors to understand available support and plan for ongoing management.