developmental and epileptic encephalopathy, 16

Developmental and epileptic encephalopathy, 16 is a severe neurodevelopmental disorder that primarily affects infants, with seizure onset typically occurring within the first weeks or months of life. The condition has a material basis in pathogenic variants in the TBC1D24 gene, where affected individuals have homozygous or compound heterozygous mutations. It is characterized by early onset seizures, delayed psychomotor development, and hypotonia, and no specific prevalence data is available. The disorder is inherited in an autosomal recessive manner, meaning that both parents must pass on a mutated gene for the condition to manifest.

The clinical presentation of this condition is marked by prominent neurological features. Affected children display cerebral atrophy, hypotonia, clonic seizures, and epileptic encephalopathy, all of which are nearly always present. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, accompanied by feeding difficulties and global developmental delay. In addition, a subset of individuals may present with sudden unexpected death in epilepsy, microcephaly, and optic atrophy. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the TBC1D24 gene. TBC1D24 plays a critical role in neuronal development and function, and disruptions in its sequence impair normal brain activity, leading to seizures and developmental challenges. The disorder is inherited in an autosomal recessive manner, which means that an individual must inherit a mutated copy of the gene from each parent. Families are encouraged to seek genetic counseling to better understand inheritance patterns and the implications for future family planning.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments or foundational therapies linked to this condition. Treatment is individualized and typically involves a multidisciplinary team to address neurological, developmental, and supportive needs. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to help families understand the condition and plan for the future.

The clinical course of developmental and epileptic encephalopathy, 16 is highly variable. It is characterized by an initial period of typical early development, followed by a phase of developmental regression, and in many cases, a period of relative stabilization with potential later motor decline. With current standards of care, outcomes vary depending on symptom severity, age at diagnosis, and access to specialized care. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with specialists and genetic counselors to explore ongoing support and management options.

Clinical trials are currently underway exploring new treatment approaches for this condition. Individuals interested in learning more about emerging therapies are encouraged to search ClinicalTrials.gov or discuss trial eligibility with their care team.