developmental and epileptic encephalopathy, 39

Developmental and epileptic encephalopathy, 39 is a very rare mitochondrial substrate carrier disorder that primarily affects the brain and muscles from infancy. It is caused by pathogenic variants in the SLC25A12 gene, which disrupt normal mitochondrial function and myelination. Most affected children present within the first year of life with severe seizures, marked developmental delays, and neurological impairments. Given its extremely low prevalence, affecting fewer than 1 in 1,000,000 individuals, families may face unique challenges in obtaining specialized care.

The clinical presentation is dominated by striking neurological and developmental abnormalities. Characteristic features include global cerebral hypomyelination seen on imaging, consistently observed seizures (including tonic and generalized-onset types), and severe muscular hypotonia. Affected children also experience significant motor delays, as evidenced by delayed ability to roll over and walk, as well as absent speech and reduced eye contact. Additional findings such as apnea, myoclonus, a single transverse palmar crease, tapered fingers, and generalized hyperreflexia further define the condition. Not all individuals experience every symptom, and severity varies considerably.

Pathogenic variants in the SLC25A12 gene are responsible for developmental and epileptic encephalopathy, 39. The SLC25A12 protein is involved in the transport of mitochondrial substrates critical for energy production and proper myelination of the brain, so its disruption leads to severe neurological deficits and developmental delays. This condition is inherited in an autosomal recessive pattern, meaning that affected children inherit one altered copy of the gene from each parent. It is also more common when parents share a common ancestor, which increases the likelihood that both carry the same rare genetic variant. Genetic counseling is recommended to discuss inheritance patterns and implications for family planning.

Currently, management focuses on supportive care and symptom management since no foundational therapies or FDA-approved treatments are available for developmental and epileptic encephalopathy, 39. Treatment is individualized with an emphasis on controlling seizures, improving motor function, and addressing developmental challenges. A multidisciplinary team—including neurologists, physical and occupational therapists, and developmental specialists—plays a critical role in ongoing surveillance and management. Regular monitoring is an essential component of care to detect and address emerging complications, and genetic counseling is recommended to help families understand all available treatment options.

Developmental and epileptic encephalopathy, 39 is a lifelong neurodevelopmental condition characterized by early-onset neurological symptoms and marked developmental challenges. Outcomes vary depending on symptom severity, age at diagnosis, and access to multidisciplinary care, with some individuals benefiting from supportive management that can improve quality of life. With current standards of care, many affected individuals experience a course that may include periods of relative stabilization despite significant early challenges. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with genetic counselors and specialist teams for personalized guidance.

There is one clinical trial underway exploring new treatment approaches for developmental and epileptic encephalopathy, 39. Individuals interested in clinical trials can search ClinicalTrials.gov or speak with their care team about eligibility.