developmental and epileptic encephalopathy, 47

Developmental and epileptic encephalopathy, 47 is an early infantile neurological condition marked by severe epilepsy and profound developmental challenges. It is caused by a mutation in the FGF12 gene, which is critical for normal neuronal function. Typically, after a period of apparently typical early development, affected children experience a phase of developmental regression and the onset of intractable seizures. Prevalence estimates are not well established, reflecting the extreme rarity of the condition.

After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills. The clinical picture consistently includes developmental regression, feeding difficulties, secondary microcephaly, limb ataxia, and tonic seizures. Children also present with epileptic encephalopathy, multifocal epileptiform discharges, cerebellar atrophy, and profound intellectual disability, indicating significant cognitive and neurological involvement. In addition, a subset of individuals may experience optic disc pallor, focal-onset seizures, cerebral visual impairment, various forms of hypotonia, agitation, axial hypotonia, bilateral tonic-clonic seizures, hypsarrhythmia, ataxia, attenuation of retinal blood vessels, absent speech, and episodes of status epilepticus. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the FGF12 gene. FGF12 plays an important role in the regulation of voltage-gated sodium channels in neurons, and disruption of its function can lead to abnormal neuronal excitability and seizure activity. It is inherited in an autosomal dominant manner, meaning that a single altered copy of the gene can result in the disorder. Families are advised to seek genetic counseling to understand the implications for current and future pregnancies.

Currently, management focuses on supportive care and symptom management as there are no treatments specifically approved for this condition. A multidisciplinary care approach is essential, involving neurologists, developmental specialists, and other experts to tailor care to each individual’s needs. Long-term management includes regular surveillance and monitoring to detect and address emerging complications early. Genetic counseling is recommended to help guide families in understanding treatment options and planning for the future.

The long-term outlook for individuals with developmental and epileptic encephalopathy, 47 is variable. This lifelong neurodevelopmental condition is characterized by an initial regression followed by a period of relative stabilization, with some individuals experiencing later motor decline. Outcomes depend on a range of factors including the severity of symptoms, age at diagnosis, and access to specialized care. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists familiar with this condition.