developmental and epileptic encephalopathy, 82

Developmental and epileptic encephalopathy, 82 is a severe multisystem disorder that primarily affects neurological development and function. It is linked to pathogenic variants in the GOT2 gene, a critical gene involved in mitochondrial metabolism. Affected individuals, most often presenting in infancy, exhibit early-onset seizures and profound developmental delays. Precise prevalence data are not well established, and the condition is considered very rare.

The clinical presentation of this condition is marked by a constellation of features affecting multiple systems. Neurologically, nearly all affected individuals experience seizures, severe intellectual disability, and delayed speech and language development. Other consistent findings include increased circulating lactate levels, neonatal hypotonia, and progressive microcephaly, all of which underscore central nervous system involvement. In addition to these core neurological symptoms, many children also exhibit recurrent infections, feeding difficulties in infancy, and hyperammonemia. A subset of individuals may develop spastic paraparesis, cerebellar vermis hypoplasia, cerebral atrophy, spastic tetraplegia, absent speech, inability to walk, hypoplasia of the corpus callosum, short stature, and decreased body weight. Not all individuals experience every feature, and severity varies considerably.

The condition is caused by pathogenic variants in the GOT2 gene. GOT2 encodes an enzyme that plays an essential role in mitochondrial metabolism, and disruption of this function leads to widespread metabolic and neurological complications. It is inherited in an autosomal recessive pattern, meaning that an affected child inherits one altered copy of the gene from each parent. This inheritance pattern implies a 25% recurrence risk for each pregnancy when both parents are carriers, and genetic counseling is recommended for families to discuss these implications.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically linked to this condition. Treatment is highly individualized and typically involves a multidisciplinary team to address the various aspects of the disorder. Supportive interventions may include antiepileptic medications to manage seizures, nutritional support to address feeding difficulties, and physical and occupational therapy to help with motor delay and challenges. Regular surveillance is an essential part of long-term care, helping to identify potential complications early on. Genetic counseling is also recommended to assist families in understanding the condition, inheritance patterns, and family planning options.

Outcomes for individuals with developmental and epileptic encephalopathy, 82 vary widely and depend on the severity of symptoms, age at diagnosis, and access to specialized care. The disease is characterized by significant neurological challenges that may lead to a progressive motor decline, although periods of stabilization are also observed. With current standards of care, many individuals benefit from improvements in seizure management and supportive therapies, and outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with genetic counselors, expert centers, and support groups for ongoing guidance and to stay informed about emerging therapies.