developmental and epileptic encephalopathy, 71

Developmental and epileptic encephalopathy, 71 is a severe neurological condition that affects brain function and development, leading to persistent seizures and significant challenges in motor and respiratory systems. It is associated with pathogenic variants in the GLS gene, which plays a role in glutaminase activity, essential for proper neural metabolism. The disorder typically presents in early infancy with symptoms such as epileptic encephalopathy, hypotonia, and abnormal EEG findings. It is very rare, affecting fewer than 1 in 1,000,000 individuals.

The clinical presentation is marked by a constellation of severe neurological symptoms. Affected individuals consistently experience epileptic encephalopathy, seizures, and hypotonia, with EEG studies showing a burst suppression pattern. Respiratory insufficiency is always present, and many patients go on to develop respiratory failure, signs of CNS demyelination, a simplified gyral pattern, and gliosis, with some also exhibiting Cheyne-Stokes respiration. Not all individuals experience all features, and severity varies considerably, with significant cognitive and developmental challenges impacting quality of life.

This condition is caused by pathogenic variants in the GLS gene, which is crucial for the proper metabolism of glutamine in the brain. The disruption in enzyme function can severely affect neural development and stability, leading to the neurological features observed in affected individuals. It is inherited in an autosomal recessive pattern, meaning that an individual must inherit two altered copies of the gene, one from each parent, to be affected. This condition is more common when parents share a common ancestor, as the likelihood of harboring the same rare genetic variant increases, and families are encouraged to seek genetic counseling to understand recurrence risks for future pregnancies.

Currently, management focuses on supportive care and symptom management. Treatment is tailored to the individual and typically involves a multidisciplinary team to address complex neurological, respiratory, and developmental needs. Supportive therapies may include seizure management, respiratory support, physical and occupational therapy, and careful developmental monitoring. Genetic counseling is recommended for affected families to discuss implications and potential risks, and patients should work closely with their healthcare team to determine the most appropriate interventions.

The long‐term outlook for individuals with developmental and epileptic encephalopathy, 71 is variable, with outcomes depending on the severity of symptoms, early intervention, and access to specialist care. With current standards of care, many individuals benefit from ongoing supportive management, although they may experience a lifelong clinical course marked by significant neurological and respiratory challenges. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with genetic counselors and specialized clinicians to get personalized guidance on managing the condition.