developmental and epileptic encephalopathy, 73

Developmental and epileptic encephalopathy, 73 is a severe neurodevelopmental condition that primarily affects the central nervous system, manifesting early in life. It is caused by pathogenic variants in the RNF13 gene, a gene that plays an important role in normal cellular and neurological functions. The condition is inherited in an autosomal dominant manner, meaning that a single altered copy of RNF13 can lead to the disorder. This disorder is very rare, affecting fewer than 1 in 1,000,000 people.

The clinical features of this condition are extensive and impact multiple organ systems, with a predominant involvement of the brain. Characteristic findings include restlessness, seizures, profound intellectual disability, hypertonia, and cerebral visual impairment, all of which are consistently observed. Other common features include flexion contractures, scoliosis, failure to thrive, hypoplasia of the corpus callosum, and sensorineural hearing impairment. In addition, some individuals may exhibit facial dysmorphisms such as a short chin, midface retrusion, and a narrow nasal bridge, along with feeding difficulties and orthopedic complications like hip dysplasia. 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, with severity varying considerably.

The underlying cause of developmental and epileptic encephalopathy, 73 is a pathogenic variant in the RNF13 gene. RNF13 is involved in cellular regulatory processes, and disruptions in its function interfere with normal neurological development. This condition is inherited in an autosomal dominant pattern, meaning that only one altered copy of the gene is sufficient to cause the disorder, thus having important implications for family members. Genetic counseling is recommended to discuss recurrence risks and family planning.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically linked to this condition. Treatment is tailored to each individual and typically involves a multidisciplinary team, including neurologists, physical therapists, and other specialists experienced in managing complex neurodevelopmental disorders. Regular surveillance is an essential part of long-term care, helping to identify potential complications related to seizures, developmental delays, and orthopedic issues before they become more serious. Genetic counseling is recommended to assist families in understanding their options and planning for the future, and patients should discuss treatment options with their healthcare team to determine the most appropriate management plan.

Developmental and epileptic encephalopathy, 73 is a lifelong neurodevelopmental condition characterized by an initial regression, followed by a period of relative stabilization and, in some individuals, later motor decline. Outcomes vary depending on symptom severity, age of diagnosis, and access to specialized care, and severity and symptoms vary widely between individuals. With current standards of care, many individuals benefit from ongoing supportive therapies, 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 and to seek genetic counseling for additional guidance.