developmental and epileptic encephalopathy, 38

Developmental and epileptic encephalopathy, 38 is a severe early infantile neurological condition characterized by intractable seizures and profound developmental impairment. It is caused by biallelic mutations in the ARV1 gene, which is essential for normal brain function. Affected children typically present in infancy with multiple, challenging neurological symptoms, although precise prevalence data is not available. The condition is recognized as very rare, and management centers on supportive care given the severity of symptoms.

Affected infants exhibit a constellation of neurological and systemic features. Characteristic findings include hypsarrhythmia, status epilepticus, multifocal seizures, and a profound intellectual disability accompanied by global developmental delay. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, with additional features such as dystonia, ataxia, poor suck, irritability, and limb hypertonia, as well as high hypermetropia and retinal abnormalities. Not all individuals experience all features, and severity varies considerably.

This condition is caused by mutations in the ARV1 gene and follows an autosomal recessive inheritance pattern. Disruption of ARV1 function interferes with normal neurological development and other vital cellular processes. Families with an affected child are encouraged to seek genetic counseling to understand the implications for family planning and recurrence risks.

Currently, management focuses on supportive care and symptom control, with treatment tailored to the individual. Although no FDA-approved treatments exist for this condition, care is typically provided by a multidisciplinary team that may include neurologists, developmental specialists, and therapists. Regular surveillance is an essential part of long-term management, with ongoing monitoring to detect and address potential complications. Patients should discuss treatment options with their healthcare team to determine the most appropriate approach for their situation.

This lifelong neurodevelopmental condition is characterized by an initial period of developmental regression followed by a phase of relative stabilization, although some individuals may experience later motor decline. Outcomes vary depending on symptom severity, age at diagnosis, and access to specialized care, and severity and symptoms vary widely between individuals. With current standards of care, many individuals benefit from ongoing supportive management, and outcomes continue to evolve as treatment strategies improve. Connecting with a genetic counselor and specialists experienced in managing this condition can provide families with critical guidance as they plan for long-term care.