developmental and epileptic encephalopathy, 36

Developmental and epileptic encephalopathy, 36 is a severe neurodevelopmental disorder that affects the brain and other organ systems. This condition is associated with variants in the ALG13 gene, which plays an important role in the glycosylation process critical for normal cellular function. It most commonly presents in early childhood, and as an X-linked disorder, its manifestation can vary between males and females, with female carriers potentially experiencing symptoms due to skewed X-inactivation. Given its very rare occurrence, it is understood to affect fewer than 1 in a million people.

Affected individuals present with a broad range of clinical features. Neurologically, severe intellectual disability, global developmental delay, and seizures including infantile spasms are consistently reported. In several cases, children may show some early developmental progress followed by a period of regression marked by loss of certain acquired skills, although the extent and timing of this regression can vary widely. In addition to the CNS involvement, physical challenges such as feeding difficulties, recurrent infections, cerebral atrophy, microcephaly, scoliosis, and various craniofacial and musculoskeletal abnormalities (for example, microretrognathia, small hands, horizontal nystagmus, low-set ears, and flexion contractures) are also prominent. Not all individuals experience every feature, and severity varies considerably.

The underlying cause of developmental and epileptic encephalopathy, 36 is linked to variants in the ALG13 gene. Disruption of ALG13 interferes with normal glycosylation processes, which are essential for proper growth and cellular functioning. Inheritance occurs in an X-linked pattern, meaning that while affected males often present with a severe phenotype, female carriers may also exhibit symptoms as a result of variable X-inactivation. It is recommended that families consider genetic counseling to better understand the implications for family planning and monitoring.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the individual through consultation with a multidisciplinary team. Due to the multi-system nature of the condition, regular surveillance is an essential part of long-term care, helping to identify potential complications such as issues related to feeding, musculoskeletal challenges, and neurologic concerns at an early stage. In the absence of approved treatments for this condition, families are encouraged to discuss available supportive interventions and consider genetic counseling as part of their ongoing care planning.

The outlook for individuals with developmental and epileptic encephalopathy, 36 is highly variable, reflecting differences in the severity of symptoms and responses to supportive care. The condition is characterized by an early impact on neurodevelopment that may be followed by a period of stabilization and, in some individuals, later motor challenges. Outcomes described in medical literature continue to evolve as standards of care improve, and many families find it beneficial to connect with specialists to navigate ongoing care. Genetic counseling remains an important next step to help manage the uncertainties and complex needs associated with the condition.

There is an active clinical trial investigating new treatment approaches for this condition. Individuals interested in learning more about ongoing research or in exploring clinical trial eligibility should consult ClinicalTrials.gov or speak with their care team.