Clinical Spectrum, Genetic Profile, and Genotype-Phenotype Correlations in Microvillus Inclusion Disease: A Systematic Review.

Abstract

Microvillus inclusion disease (MVID) is a rare congenital enteropathy caused by defects in intestinal epithelial apical trafficking and polarity. Although its genetic basis is well established, the clinical spectrum and genotype-phenotype correlations remain incompletely defined. We aimed to systematically characterize the clinical and genetic features of MVID and investigate genotype-phenotype correlations. A systematic review of MVID literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, with database searches performed from inception to August 5, 2026. A total of 118 studies comprising 336 patients were included. Intractable diarrhea was reported in 98.8% (332/336). Extraintestinal involvement was documented in 243 patients and was most often hepatic (127/243, 52.3%), with cholestasis in 80/127 (63.0%), cirrhosis in 16/127 (12.6%), and hepatic failure in 8/127 (6.3%). Among 287 patients with treatment data, 280 (97.6%) received total parenteral nutrition (TPN). Management patterns changed across reporting eras, with intestinal transplantation reported in 33.3% (23/69) of patients in 1996-2010 and 12.9% (16/124) in 2011-2026. Pathogenic variants were identified most commonly in MYO5B, followed by STXBP2, STX3, and UNC45A. Bi-allelic null MYO5B variants were associated with earlier onset than bi-allelic non-null variants (p < 0.001); in severe hepatic involvement, the presence of at least one null MYO5B variant was associated with reduced liver-intestine transplant-free survival (log-rank p = 0.040). MVID is characterized by intractable diarrhea and substantial hepatic involvement. Molecular diagnosis clarifies the genetic etiology and provides a basis for genotype-informed clinical stratification. Treatment strategies should be interpreted in an era-specific context. Systematic Review Registration: PROSPERO (CRD42024503464).