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

MYO5B

Defective apical trafficking and polarity of intestinal epithelial cells; pathogenic variants most often in MYO5B, followed by STXBP2, STX3 and UNC45A

This systematic review, conducted according to PRISMA with PROSPERO registration (CRD42024503464), includes 118 studies and 336 patients with microvillus inclusion disease (MVID). Intractable diarrhoea was present in 98.8% of patients and extra-intestinal involvement in 243, most often hepatic (52.3%), with cholestasis in 63.0% of those. Of 287 patients with treatment data, 97.6% received total parenteral nutrition, and intestinal transplantation fell from 33.3% (1996-2010) to 12.9% (2011-2026). Pathogenic variants mostly affect MYO5B; bi-allelic null MYO5B variants are associated with earlier onset than non-null variants (p < 0.001), and at least one null variant is associated with reduced liver-intestine transplant-free survival in severe hepatic involvement (log-rank p = 0.040).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Stratification by MYO5B variant type (null versus non-null) is the actionable result for prognosis and genetic counselling. Like any synthesis of published cases, it inherits publication bias and heterogeneity of care, which the authors acknowledge by asking that treatments be read by era. A review that makes a MYO5B variant more informative at interpretation in exome/genome is worth more than yet another argument for a panel.

Analysis by Dr Thibaut Benquey