developmental and epileptic encephalopathy 105 with hypopituitarism

Developmental and epileptic encephalopathy 105 with hypopituitarism is a severe, early-onset neurological condition that affects both brain development and pituitary function. The disorder presents within the first weeks or months of life and is marked by profound developmental impairments and seizure activity. It arises from homozygous or compound heterozygous mutations in the HID1 gene and is inherited in an autosomal recessive pattern. Precise prevalence estimates are not well established, and severity varies widely among affected individuals.

Clinically, affected individuals consistently exhibit motor delay, synophrys, absent speech, and pituitary hypothyroidism, all of which are observed in 100% of cases. Seizure activity is common and can include bilateral tonic-clonic, tonic, myoclonic, and focal impaired awareness seizures, accompanied by abnormal EEG patterns such as generalized slow activity and focal sharp slow waves. Other neurological and craniofacial features, including a thin corpus callosum, long eyelashes, and anterior pituitary hypoplasia, are frequently reported, with additional findings like hypotonia, spasticity, and brain atrophy present in a subset of patients. Not all individuals experience all features, and severity varies considerably, highlighting the variable neurodevelopmental and endocrine involvement in this condition.

This condition is caused by pathogenic variants in the HID1 gene, which plays a crucial role in normal cellular functioning and intracellular processes. Disruption of this gene leads to abnormalities in brain development and pituitary function. It is inherited in an autosomal recessive manner, meaning that an affected individual has mutations in both copies of the gene. Consequently, when both parents are carriers, there is a 25% recurrence risk for each pregnancy. Genetic counseling is recommended to help families understand the implications for future pregnancies.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the individual’s needs. A multidisciplinary team, including neurology, endocrinology, and developmental specialists, guides the care, addressing both neurological and endocrine aspects of the disorder. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Patients and families are encouraged to discuss treatment options with their healthcare team, and genetic counseling is recommended to support informed decision making.

This lifelong neurodevelopmental condition is characterized by early impairments and seizure activity, with outcomes that vary widely among affected individuals. With current standards of care, many individuals benefit from early supportive interventions, although the course may include periods of stabilization and variable progression over time. Outcomes described in medical literature continue to evolve as standards of care improve, and families are advised that individual experiences can differ significantly. Connecting with specialized healthcare providers and genetic counseling can provide valuable guidance for ongoing management.