developmental and epileptic encephalopathy, 67

Developmental and epileptic encephalopathy, 67 is a neurological disorder that primarily affects brain function in early childhood. It is characterized by abnormal electrical activity in the brain and is associated with pathogenic variants in the CUX2 gene. Affected children typically present with global developmental delay, intellectual disability, and multiple types of seizures. Precise prevalence estimates are not well established, and the condition is understood to be rare.

The clinical presentation is marked by a combination of neurological and developmental features. Almost all affected individuals show an abnormal EEG pattern, intellectual disability, and global developmental delay. Seizure types such as bilateral tonic-clonic, generalized myoclonic, generalized non-motor (absence), and tonic seizures are observed in a notable proportion of cases, while other features including focal hemiclonic seizures, atonic seizures, and hypsarrhythmia tend to occur in a subset of affected children. In addition, some children display movement disturbances such as dyskinesia, dystonia, athetosis, and recurrent hand flapping, with reduced eye contact and cerebellar atrophy noted in a smaller percentage. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, and not all individuals experience all features as severity varies considerably.

Pathogenic variants in the CUX2 gene, which plays a critical role in neuronal development, are responsible for this condition. It is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene is sufficient to cause the disorder. As a result, a family history may be present, and genetic counseling is recommended to help families understand their risks and the implications for family planning.

Currently, management focuses on supportive care and symptom management, as there are no treatments that are specifically approved for this condition. Care typically involves a multidisciplinary team who guide both acute interventions and long-term surveillance. Regular monitoring plays an essential role in identifying any emergent complications and in optimizing individualized therapies, which may include seizure management, developmental therapies, and supportive services. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended as part of comprehensive care.

Outcomes vary widely among affected individuals. While many children experience an initial developmental regression, there may be a subsequent period of stabilization, and in some cases, later improvements are observed with appropriate supportive care. Severity and symptoms vary widely between individuals, and outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition as well as with genetic counselors to guide future planning.