developmental and epileptic encephalopathy, 28

Developmental and epileptic encephalopathy, 28 is a severe early-onset neurological condition characterized by frequent seizures and profound developmental challenges. It is caused by pathogenic variants in the WWOX gene, which plays an important role in cellular regulation and brain development. Affected infants typically exhibit multiple distinctive physical features and abnormal neurological findings from the earliest stages of life. Because precise prevalence data is not available, the condition is understood to be extremely uncommon.

Individuals with this condition display a constellation of clinical features that primarily affect the central nervous system. Characteristic findings include a high forehead, epicanthus, and bilateral tonic-clonic seizures, which occur along with other manifestations of epileptic encephalopathy such as status epilepticus and abnormal EEG patterns. Additional observations, noted in all affected individuals, include hand clenching, hypoplasia of the corpus callosum, global developmental delay, a long philtrum, cerebral calcification, and a simplified gyral pattern. In some patients, features such as hypokinesia, spasticity, reduced eye contact, hyperreflexia, secondary microcephaly, sudden unexpected death in epilepsy, and epileptic spasms may also be observed. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the WWOX gene. The WWOX gene is involved in diverse cellular processes including regulation of apoptosis and proper brain development, and mutations can significantly disrupt these functions. In this autosomal recessive disorder, an affected individual inherits two mutated copies of the gene – one from each parent – which explains the absence of a family history in many cases. Families are encouraged to seek genetic counseling to better understand the implications for future pregnancies and to discuss recurrence risks.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically for this condition. Treatment plans are highly individualized and commonly rely on a multidisciplinary team – including neurologists, epileptologists, and developmental specialists – to address seizure control, developmental delays, and other complications. Regular surveillance is an essential part of long-term care, with ongoing monitoring helping to identify potential complications early. Genetic counseling is recommended to provide families with guidance regarding treatment options and future family planning.

The course of developmental and epileptic encephalopathy, 28 is highly variable. With current standards of care, outcomes differ depending on the severity of neurological involvement, age at diagnosis, and access to specialized support. Outcomes described in medical literature continue to evolve as standards of care improve, and many families benefit from connecting with specialists familiar with the condition. That while the condition is lifelong, the specific progression may range from stabilization after initial challenges to further complications later in life.

Clinical trials are underway exploring new treatment approaches for developmental and epileptic encephalopathy, 28. Individuals interested in these investigational therapies can search ClinicalTrials.gov or discuss eligibility options with their care team.