developmental and epileptic encephalopathy, 76

Developmental and epileptic encephalopathy, 76 is a severe neurodevelopmental disorder marked by early onset seizures and significant delays in cognitive and motor skills. It is caused by pathogenic variants in the ACTL6B gene, which plays a critical role in normal brain development. The condition generally presents in early childhood and frequently includes profound intellectual challenges, absent speech, and abnormal muscle tone. Precise prevalence data are not well established, reflecting the rarity and complexity of the disorder.

Individuals with this condition exhibit a range of neurological and developmental challenges. Core features include persistent seizures, intellectual disability, absent speech, and axial hypotonia, while many also experience difficulties with walking and feeding in infancy. Additional clinical findings, observed in a subset of cases, include multifocal epileptiform discharges, hypoplasia of the corpus callosum, microcephaly, cerebral atrophy, delayed central nervous system myelination, cerebellar atrophy, and periventricular white matter hyperintensities. Not all individuals experience all features, and the severity varies considerably, underscoring the variable impact on cognitive and neurological function.

This condition is caused by pathogenic variants in the ACTL6B gene, which is important for the development and proper functioning of the brain. It is inherited in an autosomal recessive pattern, meaning that an affected individual inherits one altered copy of the gene from each parent. This pattern of inheritance highlights the importance of genetic counseling for families, particularly in contexts where parents may share a common ancestor.

Currently, management focuses on supportive care and symptom relief, as no treatments have been specifically approved for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team to address seizures, motor difficulties, feeding challenges, and communication delays. Genetic counseling is recommended to help families understand inheritance patterns and to explore long-term care and support options. Patients should discuss treatment options with their healthcare team to determine which therapies may be best suited for their situation.

This condition is a lifelong neurodevelopmental disorder with a course that can vary widely between individuals. Outcomes described in medical literature continue to evolve as standards of care improve, and the severity and range of symptoms differ significantly from one person to another. Many individuals experience an initial period of significant neurological impairment followed by phases of stabilization, although later challenges may emerge over time. Families often find it helpful to connect with genetic counselors and specialized care centers to receive ongoing support and up-to-date information.