Connective tissue and genetics in the pathogenesis of rectal prolapse: A scoping review.

Abstract

Rectal prolapse can occur in individuals who lack the established risk factors (constipation, obstetric trauma and advanced age). A recognised association with hereditary connective tissue diseases may indicate a role for variants in connective tissue-related genes in the pathogenesis of the disease. This scoping review evaluates the evidence supporting this. A scoping review was performed using a systematic search of Medline, Embase, CINAHL and The Cochrane Library in March 2026. Studies describing any of the following in the context of rectal prolapse were included: epidemiology in individuals with hereditary connective tissue disease, tissue morphology, disease heritability or genetic testing of affected individuals. Study design and key findings were collated and summarised. Sixty of 4442 screened sources were eligible for inclusion. Rectal prolapse is common in Ehlers-Danlos Syndrome (3.2%-18%), Marfan's syndrome (6%) and joint hypermobility (4.9%-11%). Hypermobility is associated with post-operative recurrence and younger age of onset. Abnormal pelvic floor collagen and elastin organisation, reduced myofibroblast density and increased dermal elastin density were key examples of abnormal tissue morphology in individuals with rectal prolapse. Patterns of heritability have not been adequately evaluated, but novel variants in connective tissue-related genes (e.g. EFEMP1, COLGALT2, FBLN5 and TNXB) are reported in individuals with rectal prolapse. An association with hereditary connective tissue disease, and the presence of abnormal morphology of the extracellular matrix characterise the relationship between connective tissue and rectal prolapse. There is evidence to support a genetic association with rectal prolapse, though further characterisation of heritability and larger scale association studies are required.