developmental and epileptic encephalopathy 104

Developmental and epileptic encephalopathy 104 is a neurodevelopmental disorder marked by early-onset seizures and delays in multiple areas of development, including speech, motor skills, and cognition. It is associated with pathogenic variants in the ATP6V0A1 gene, which plays an important role in cellular processes. The condition follows an autosomal dominant inheritance pattern and typically presents in infancy. Precise prevalence estimates are not well established, and there is considerable variability in the severity of symptoms between affected individuals.

The clinical presentation of this condition is primarily characterized by persistent seizures, such as focal impaired awareness seizures and bilateral tonic-clonic seizures that are always present, along with epileptic spasms and hypsarrhythmia in a significant number of cases. In addition, all affected individuals experience global developmental delay, delayed speech and language development, delayed motor milestones like walking and rolling over, and intellectual disability. Affected children may also exhibit additional features including hyperactivity, poor suck in infancy, self-injurious behavior, autistic behaviors, visual impairment, and agitation, though not every individual will experience every symptom. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the ATP6V0A1 gene. It is inherited in an autosomal dominant pattern, which means that a single altered copy of the gene can lead to the disorder, and an affected individual has a 50% chance of passing the variant on to each child. That even within the same family, the severity and specific symptoms can vary significantly, reflecting variable expressivity. Genetic counseling is recommended to help families understand the implications for family planning.

Currently, management focuses on supportive care and symptom management, with treatment plans tailored to the needs of the individual. A multidisciplinary team approach is essential and may include neurologists, developmental specialists, and therapists who work together to control seizures and support developmental progress. Regular surveillance is an essential part of long-term care, helping to identify potential complications early and adjust interventions as needed. Patients should discuss treatment options with their healthcare team to determine the best approach, and genetic counseling is advised for affected families.

The long-term outlook for individuals with developmental and epileptic encephalopathy 104 is highly variable, with outcomes depending on the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, many individuals benefit from supportive, multidisciplinary management, although the course may include challenges related to ongoing seizure activity and developmental impairments. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition to navigate care and treatment decisions.