developmental and epileptic encephalopathy, 63

Developmental and epileptic encephalopathy, 63 is a severe neurodevelopmental condition that primarily affects young children, presenting with early onset seizures and significant delays in motor and speech development. The condition is associated with pathogenic variants in the CPLX1 gene, which plays an important role in synaptic vesicle release in the brain. Affected individuals typically present in infancy with multiple neurological symptoms, and the disruption in brain function leads to a complex clinical picture. Precise prevalence data are not well established, and severity can vary considerably between individuals.

The clinical features of this condition are predominantly neurological. All affected individuals exhibit seizures, including bilateral tonic-clonic, generalized myoclonic, and generalized tonic seizures, along with epileptic encephalopathy that fundamentally disrupts normal brain function. In addition, there is global developmental delay, intellectual disability, absent speech, and an inability to walk, with delays in acquiring motor skills and poor head control. Other features, such as hypotonia, thin upper lip vermilion, cleft palate, cerebral palsy, and various craniofacial differences (including midface retrusion, long philtrum, hypertelorism, and thick eyebrows), are seen in a subset of individuals. Not all individuals experience all features, and severity varies considerably.

This condition results from pathogenic variants in the CPLX1 gene, which encodes complexin 1, a protein essential for proper synaptic function and neurotransmitter release in the brain. It is inherited in an autosomal recessive pattern, meaning that an affected child has received two altered copies of the gene, one from each asymptomatic carrier parent. Given this inheritance pattern, there is a 25% recurrence risk for future pregnancies when both parents are carriers. Genetic counseling is recommended to help families understand inheritance patterns, assess recurrence risks, and consider family planning options.

Currently, management focuses on supportive care and symptomatic treatment, as no FDA-approved or foundational therapies are specifically linked to this condition. Treatment is tailored to each individual and typically involves a multidisciplinary team—including neurologists, developmental pediatricians, and therapists—to address both seizure control and developmental needs. Regular surveillance is an essential part of long-term care, helping to identify potential complications early and guide adjustments in therapy. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended to provide further guidance.

Outcomes for developmental and epileptic encephalopathy, 63 vary widely depending on symptom severity, age of diagnosis, and access to specialized care. The condition is characterized by significant neurodevelopmental challenges and lifelong epilepsy, with a clinical course that may include periods of relative stabilization and times when symptoms are more pronounced. Outcomes described in medical literature continue to evolve as standards of care improve, and while supportive care has advanced, individual trajectories can differ significantly. Families often find it helpful to connect with specialists familiar with this condition to better understand and manage the complex nature of its progression.

Clinical trials are underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility, as ongoing research continues to evolve the understanding and management of these complex neurodevelopmental challenges.