cortical dysplasia-focal epilepsy syndrome

Cortical dysplasia-focal epilepsy syndrome is a neurodevelopmental disorder characterized by the onset of intractable seizures and cognitive challenges after a period of normal early development. The condition is caused by mutations in the CNTNAP2 gene, which plays an important role in neural connectivity and brain development. It typically presents in early childhood, with affected children experiencing seizures between the ages of 1 and 9 years, followed by language regression and behavioral changes. Although precise prevalence data are not available, the condition is considered rare and its outcomes remain variable as research and care continue to evolve.

After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, particularly in language and social interaction. The clinical features are predominantly neurological and include intractable focal seizures, both focal impaired awareness and focal-onset seizures, as well as bilateral tonic-clonic seizures. In addition, intellectual disability and receptive language delay are obligate features, accompanied by hyperactivity, impulsive behaviors, and a high likelihood of later meeting criteria for autism spectrum disorder. Other common features include macrocephaly, strabismus, and even manifestations such as schizophrenia, with the understanding that not all individuals experience all features and severity varies considerably.

This condition is caused by mutations in the CNTNAP2 gene. CNTNAP2 encodes contactin-associated protein-like 2, a protein important for the development and function of the nervous system. Cortical dysplasia-focal epilepsy syndrome follows an autosomal recessive inheritance pattern, meaning that affected individuals have inherited two mutated copies of the gene, one from each parent. Genetic counseling is recommended to help families understand the inheritance risk, especially in families where parents share a common ancestor.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically linked to this condition. Seizure control and management of behavioral concerns are addressed through a multidisciplinary approach, which may include neurologists, developmental pediatricians, and other specialists. Long-term care involves regular surveillance to monitor neurological development and to identify emerging complications early. Genetic counseling is recommended, and patients should discuss treatment options with their healthcare team to determine the most appropriate interventions for their situation.

Cortical dysplasia-focal epilepsy syndrome is a lifelong neurodevelopmental condition characterized by an initial regression following typical early development, followed by a period of relative stabilization and, in some individuals, later motor and cognitive challenges. Outcomes vary depending on symptom severity, age at diagnosis, and access to specialized care. With current standards of care and ongoing improvements in research and clinical management, many individuals experience stabilization of symptoms, although the overall trajectory can differ significantly among patients. Outcomes described in medical literature continue to evolve as standards of care improve, and families are encouraged to connect with genetic counselors and specialized care teams for ongoing support.

Clinical trials are underway exploring new treatment approaches for cortical dysplasia-focal epilepsy syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility and emerging therapies.