developmental and epileptic encephalopathy, 46

Developmental and epileptic encephalopathy, 46 is an early-onset neurodevelopmental disorder that typically presents in infancy with significant seizure activity and delays in cognitive and motor development. The condition is caused by mutations in the GRIN2D gene, which plays a key role in brain signaling. It is inherited in an autosomal dominant pattern, meaning that a single altered copy of the gene is sufficient to lead to the condition. Precise prevalence estimates are not well established, and the clinical presentation can vary considerably between affected individuals.

Affected individuals most commonly present with epileptic encephalopathy and seizures, alongside global developmental delay that impacts cognitive and motor skills. Universal features include pes planus, axial hypotonia, and limb hypertonia, while a subset of patients may also experience microcephaly, feeding difficulties, cerebral visual impairment, and other challenges such as drooling, tremor, dysphagia, and hypsarrhythmia. These features are primarily neurological and developmental in nature, highlighting the impact on brain function. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the GRIN2D gene, which is integral to normal neuronal communication. It is inherited in an autosomal dominant manner, meaning that a single mutated copy of the gene can lead to the disorder. While the precise origin of the mutation may vary from case to case, genetic counseling is recommended to help families understand the inheritance implications and discuss personalized recurrence risks.

Currently, management focuses on supportive care and symptom management, as no treatments have been specifically approved for this condition. Treatment is tailored to the individual and typically involves a multidisciplinary team that addresses seizure control, developmental interventions, and supportive therapies. Regular surveillance is an essential part of long-term care, helping to identify potential complications early. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended for guidance regarding inheritance and family planning.

The long-term outlook for developmental and epileptic encephalopathy, 46 is variable, with outcomes depending on the severity of symptoms, timing of diagnosis, and access to specialized care. With current standards of care, many individuals benefit from interventions that help manage seizures and support developmental progress. Outcomes described in medical literature continue to evolve as standards of care improve, and while some individuals may face ongoing challenges, others may experience periods of stabilization. Families are encouraged to connect with specialists and genetic counselors to discuss individualized care and long-term management strategies.

There is an active clinical trial exploring potential treatment approaches for this condition. Clinical trials are underway investigating new therapies, and individuals interested in research opportunities can search ClinicalTrials.gov or consult their care team about eligibility.