Phenotype and genotype in hereditary chronic intestinal pseudo-obstruction with small intestine involvement

Chronic intestinal pseudo-obstruction (CIPO) is a rare and severe intestinal motility disorder with poor long-term prognosis and high mortality rate, especially when the small intestine is involved. Due to the non-specificity of clinical symptoms, CIPO has long faced diagnostic challenges. With the advancements of sequencing technology, many hereditary CIPOs have been identified. Establishing the relationship between genotype and phenotype of hereditary CIPO to make diagnosis early has become a focal point for clinicians. This article reviewed hereditary CIPO with small intestine involvement reported in the past 25 years, collecting patients’ phenotypic and genetic information, and categorizing them into several groups for comparative analysis based on the involved intestinal segments and pathological features. A total of 75 cases were included. We found that the CIPO group with both small and large intestine involvement (SLI) had a higher proportion of bloating and constipation, while the CIPO group with isolated small intestine involvement (ISI) had a higher proportion of diarrhea and was more likely to be associated with mitochondrial disorders. Hereditary CIPO patients associated with mitochondrial disorders exhibited a later age of onset, higher prevalence of malnutrition, and more prominent multi-system involvement. Other myogenic CIPO patients, in which ACTG2 was the most frequently mutated gene, showed more frequent SLI and a high incidence of malrotation. This article preliminarily explores the correlation between genotype and phenotype in hereditary CIPO, focusing specifically on patients with small intestine involvement, aiming to provide valuable clues for the early identification and diagnosis of hereditary CIPO with small intestine involvement.