developmental and epileptic encephalopathy, 49

Developmental and epileptic encephalopathy, 49 is an early-onset neurological condition caused by mutations in the DENND5A gene. It is characterized by severe impairment in brain development, leading to profound epileptic activity and global developmental delay. Affected infants typically present in early life with striking features including abnormal facial characteristics and seizures, with no single prevalence estimate established. The disorder primarily impacts the central nervous system, resulting in significant cognitive and neurological challenges that require ongoing management.

Individuals with developmental and epileptic encephalopathy, 49 commonly present with a constellation of clinical features that affect both appearance and neurological function. Characteristic findings include microcephaly, coarse facial features, thick eyebrows, an everted lower lip vermilion, open mouth, tented upper lip vermilion, short philtrum, prominent nose, and long eyelashes. Neurologically, bilateral tonic-clonic seizures, abnormal EEG findings, and epileptic encephalopathy are always reported, alongside severe global developmental delay that impacts cognitive and adaptive skills. In addition, a subset of affected individuals may experience features such as cerebellar vermis hypoplasia, spastic tetraplegia, absent speech, myoclonus, exaggerated startle response, and anxiety. Not all individuals experience all features, and severity varies considerably.

The underlying cause of this condition is a mutation in the DENND5A gene, which plays a critical role in neuronal development. It is inherited in an autosomal recessive pattern, meaning that an affected individual has received one mutated copy of the gene from each parent. This inheritance pattern implies that parents, who each carry one copy of the altered gene, typically do not show symptoms but have a 25% chance with each pregnancy of having an affected child. Families are encouraged to seek genetic counseling to better understand their risks and options for future family planning.

Currently, management of developmental and epileptic encephalopathy, 49 focuses on supportive care and symptom management through a multidisciplinary approach. Although there are no FDA-approved treatments specifically for this condition, care is tailored to each individual and generally involves regular surveillance to monitor for neurological complications and other emerging issues. Health care providers may recommend therapies such as antiepileptic medications, physical and speech therapy, and other interventions aimed at improving quality of life. Families should discuss treatment options with their healthcare team and consider connecting with specialists experienced in managing complex neurodevelopmental conditions.

The overall course of developmental and epileptic encephalopathy, 49 is highly variable, with outcomes depending on the severity of neurological involvement and access to specialized care. With current standards of care, many affected individuals experience significant challenges related to cognitive and motor functions, while some aspects of the condition may stabilize over time. Outcomes described in medical literature continue to evolve as standards of care improve, and variability in clinical presentation means that not all individuals will experience the same degree of impairment. Families often find it helpful to connect with genetic counselors and specialists familiar with this condition to receive guidance and support for long-term management.