Clinical outcomes and molecular profile of patients with Carmi syndrome: A systematic review and evidence quality assessment.

Purpose: Carmi syndrome is a rare genetic disorder characterized by junctional epidermolysis bullosa (JEB) and pyloric atresia (PA). We reviewed the clinicopathologic and molecular features of patients with Carmi syndrome to identify predictors of clinical outcome and guide surgical PA repair.

Methods: A PRISMA-compliant systematic literature review of PubMed, CINAHL, and the Cochrane Library was performed.

Results: 63 original studies including a total of 100 patients were included. PA type 1 and 2 were equally prevalent (47.2%, 95% CI: 34.4-60.3). Heineke-Mikulicz pyloroplasty (96%, 95% CI: 78.8-99) and gastroduodenostomy (72%, 95% CI: 52.2-85.9) were the most common type 1 and 2 PA repairs, respectively. Seventy lethal cases were identified (74.5%, 95% CI: 64.8-83.5). Of the 73 patients that received an operation, 49 died (67.1%, 95% CI: 55.7-76.8) and 24 survived (32.9%, 95% CI: 23.2-44.3). Integrin α6β4 expression was absent or markedly reduced in lethal cases. Integrin α6, plectin-1, cephalic integrin β4 (exon 3 to intron 11), and premature termination codon mutations were also associated with poor prognosis.

Conclusions: Although Carmi syndrome typically has poor prognosis, 1 in 4 patients exhibits nonlethal phenotypes. Immunofluorescence mapping and genetic consultation can guide surgical intervention and provide valuable family planning information.

Evidence Rating/classification: Prognosis study, Level IV.