developmental and epileptic encephalopathy, 29

Developmental and epileptic encephalopathy, 29 is an early-onset neurological disorder that presents in infancy and is characterized by severe impairments in motor and cognitive development. The condition is caused by pathogenic variants in the AARS1 gene, which plays a critical role in protein synthesis. Affected children experience profound developmental delays, movement abnormalities, and seizures. Precise prevalence estimates are not well established, and the disorder is inherited in an autosomal recessive pattern.

The clinical presentation is marked by a constellation of neurological and musculoskeletal features. Characteristically, affected individuals show rocker bottom feet, areflexia, global developmental delay, and a range of movement disorders including limb dystonia, chorea, spasticity, and blepharospasm. Additional manifestations include cerebral atrophy, microcephaly, orofacial dyskinesia, and myoclonic seizures. In some cases, features such as intrauterine growth retardation, axial hypotonia, short stature, CNS hypomyelination, nystagmus, and hip dislocation are present. Not all individuals experience all features, and severity varies considerably.

This condition is caused by pathogenic variants in the AARS1 gene, which encodes an enzyme essential for the proper charging of tRNAs during protein synthesis. The loss of proper enzyme function disrupts normal cellular protein production, critically affecting neurological and muscular development. It is inherited in an autosomal recessive pattern, meaning that an affected individual has received a mutated copy of the gene from each parent. Families are advised to seek genetic counseling to better understand the recurrence risk and implications for future pregnancies.

Currently, management focuses on supportive care and symptom management, with treatment approaches tailored to each individual’s needs. A multidisciplinary team, including neurologists, developmental specialists, and therapists, is typically involved to provide comprehensive care and regular surveillance to monitor for complications. Since no specific treatments have been approved for this condition, interventions are aimed at optimizing developmental potential and quality of life. Patients should discuss treatment options with their healthcare team, and genetic counseling is recommended for affected families.

This lifelong neurodevelopmental condition is associated with significant challenges in motor and cognitive development. The course of the disorder can vary widely between individuals, with some experiencing more severe impairments than others. With current standards of care, many individuals benefit from supportive interventions that help maximize developmental potential, although the condition may progress, stabilize, or show a variable course over time. 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.

Clinical trials are underway exploring new treatment approaches for this condition. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.