developmental and epileptic encephalopathy, 77

Developmental and epileptic encephalopathy, 77 is a complex condition that primarily affects early neurodevelopment and is characterized by seizures along with multiple congenital anomalies. The condition results from pathogenic variants in the PIGQ gene, which plays a critical role in glycosylphosphatidylinositol (GPI) biosynthesis. It generally presents in infancy with hypotonia, feeding difficulties, and distinctive facial and physical features, although precise prevalence estimates are not well established. Because it follows an autosomal recessive pattern, the disorder tends to occur when both parents carry a variant in the PIGQ gene.

Affected infants typically present with poor head control and floppy infant characteristics, accompanied by feeding difficulties and myoclonic seizures. In addition, individuals exhibit a range of consistent physical features, including coarse facial features, a long philtrum, anteverted nares, a thin upper lip vermilion, and full cheeks. Other commonly observed clinical signs include cerebral visual impairment, vertical nystagmus, and musculoskeletal findings such as abdominal wall muscle weakness, diastasis recti, and scoliosis. Not all individuals experience every feature, and severity varies considerably.

This condition is caused by pathogenic variants in the PIGQ gene, which is involved in the biosynthesis of glycosylphosphatidylinositol, an important molecule that anchors proteins to the cell membrane. It is inherited in an autosomal recessive manner, meaning that an affected individual has inherited a defective copy of the gene from each parent. As a result, both parents are typically asymptomatic carriers, and there is an approximately 25% chance with each pregnancy of having an affected child. Genetic counseling is recommended for affected families to further understand these implications.

Currently, management focuses on supportive care and symptom management, with treatment tailored to the individual. A multidisciplinary care approach is critical, with various specialists addressing neurological issues, feeding difficulties, musculoskeletal concerns, and other associated features. Regular surveillance is an essential part of long-term management, helping to identify potential complications before they become serious. Families are encouraged to engage with genetic counseling and to discuss available treatment options with their healthcare team to determine the best approach for their situation.

The course of developmental and epileptic encephalopathy, 77 is highly variable, with outcomes dependent on the severity of symptoms and the age at which diagnosis and supportive interventions begin. With current standards of care, many individuals benefit from a multidisciplinary management approach that addresses both neurological and systemic issues. Outcomes described in medical literature continue to evolve as standards of care improve, and families are advised to connect with specialists and genetic counselors for ongoing guidance and support. That severity and symptoms vary widely between individuals.