Epidermolysis bullosa simplex with pyloric atresia

Epidermolysis bullosa simplex with pyloric atresia (EBS-PA) is an extremely rare and severe subtype of epidermolysis bullosa simplex, a group of inherited skin fragility disorders. This condition is characterized by two hallmark features present at birth: widespread blistering of the skin and mucous membranes, and pyloric atresia — a congenital obstruction of the pylorus (the outlet of the stomach into the small intestine). The skin blistering results from defects in proteins that maintain the structural integrity of the basal layer of the epidermis, leading to intraepidermal separation with minimal trauma. Pyloric atresia causes an inability to pass stomach contents into the intestine, resulting in feeding intolerance and vomiting in the newborn period. EBS-PA is caused by biallelic pathogenic variants in the PLEC gene (encoding plectin), and less commonly in the ITGA6 or ITGB4 genes (encoding integrin alpha-6 and integrin beta-4, respectively). Plectin is a cytoskeletal linker protein critical for mechanical stability in epithelial cells, muscle, and other tissues. Affected infants typically present immediately after birth with generalized skin blistering, aplasia cutis (areas of absent skin), and signs of gastrointestinal obstruction due to pyloric atresia. Additional features may include urological abnormalities and, in some cases, late-onset muscular dystrophy in surviving patients with PLEC mutations. The prognosis for EBS-PA is generally very poor, with many affected infants dying in the neonatal period or early infancy due to complications such as sepsis, fluid and electrolyte imbalances, and failure to thrive. Surgical correction of the pyloric atresia is necessary for survival but does not address the underlying skin fragility. Treatment is primarily supportive and includes meticulous wound care to prevent infection, nutritional support, pain management, and surgical intervention for the gastrointestinal obstruction. There is currently no cure or disease-modifying therapy available. Genetic counseling is recommended for affected families.

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