Family History and Clinical Severity of Functional Constipation: Sex-Stratified Findings From the FAMI-CON+ Multicenter Retrospective Study

INTRODUCTION: Functional constipation (FC) is one of the most prevalent disorders of gut-brain interaction (DGBIs), associated with reduced quality of life and increased morbidity and mortality. Although several studies have examined risk factors in children, research focusing on adult populations is considerably limited. The present study investigated the association between family history and the clinical phenotype of FC using an adult cohort and a standardized constipation scoring system, building on prior population-based findings suggesting familial influences on disease prevalence and severity. METHODS: A retrospective multicenter study of adults diagnosed with FC according to the Rome IV criteria was conducted at 9 Japanese centers. Collected data included family history, demographic characteristics, age at symptom onset, modified Constipation Scoring System (mCSS) scores before and after treatment, and prescribed medications, with onset age and mCSS selected to evaluate potential familial associations with earlier disease onset and greater symptom severity. RESULTS: Data from 266 patients were analyzed. A family history was present in 30.1% of patients and was more common in women (34.5%) than in men (22.1%) (OR 1.86, 95% CI 1.04-3.31; p = 0.037). Among the women, a positive family history was associated with earlier onset (median 30 vs. 40 years, p = 0.043) and higher baseline mCSS scores (median 11 vs. 8, p = 0.039), whereas no significant associations were observed in men. Subscore analyses showed higher ratings for "feeling of incomplete evacuation" and "minutes in lavatory per attempt" in women with a family history. Although women with a family history required more medications, treatment response, as measured by improvement in mCSS, was comparable to those without such history. CONCLUSION: Family history is associated with sex-specific differences in the clinical presentation of FC. This pattern may reflect interactions between genetic susceptibility, hormonal factors, and shared familial environments.