Histogenetic Classification Predicts Outcomes in 130 Adults With Chronic Intestinal Pseudo-Obstruction

INTRODUCTION: Chronic intestinal pseudo-obstruction (CIPO) is a rare, heterogeneous disorder associated with severe morbidity. Genetic variants and histopathological lesions have been described, but their combined evaluation has rarely been assessed in adult CIPO cohorts. This study aimed to evaluate the contribution of integrated genetic and histological analyses in adults with CIPO. METHODS: We conducted a retrospective observational study of adults with CIPO followed at a national tertiary referral center. Patients with CIPO underwent genomic profiling, including next-generation sequencing (NGS) panel, long-range polymerase chain reaction (PCR), whole-exome, and whole-genome sequencing. Centralized histological analysis of full-thickness bowel biopsies and resections was integrated with genomic data to assess their combined impact on disease outcomes. RESULTS: The cohort included 130 patients (75 females, 55 males, aged 19-74 years), followed for up to 64 years. Genetic and histological analyses characterized 82% of the patients (genetic diagnosis: n = 65/112, 58%; histological diagnosis: n = 73/96, 76%), allowing the classification of patients into 6 groups: monogenic myopathy (n = 42), mitochondriopathy (n = 19), unspecified myopathy (n = 26), autoimmune myopathy (n = 8), neuropathy (n = 9), and others (n = 26). Survival and postoperative outcomes differed across groups. In this cohort, patients with monogenic myopathy had the most favorable long-term survival (adjusted hazard ratio: 0.06, 95% CI: 0.01-0.42; P = 0.004) and higher rates of improvement after bowel resection compared with other patients. DISCUSSION: Integrated genetic and histological evaluation informed etiological classification in adults with CIPO and may aid clinical decision-making.