# Clinical, manometric, genetic, and histologic associations in pediatric intestinal pseudo‐obstruction: A case series

## TL;DR

This study examines the clinical and genetic features of pediatric intestinal pseudo-obstruction, finding that ACTG2 mutations are linked to myopathic cases and highlighting the genetic diversity in neuropathic cases.

## Contribution

The study identifies ACTG2 mutations as a key genetic cause of myopathic PIPO and reveals greater genetic variability in neuropathic PIPO.

## Key findings

- ACTG2 mutations were found in all myopathic PIPO cases, linking them to a specific genetic cause.
- Neuropathic PIPO showed more genetic variability with fewer known disease-causing variants.
- Surgical interventions were more common in myopathic PIPO compared to other subtypes.

## Abstract

Pediatric intestinal pseudo‐obstruction (PIPO) is a severe bowel motility disorder characterized by impaired propulsion of gastrointestinal contents without mechanical obstruction. PIPO encompasses congenital and acquired disorders, including neuropathies, myopathies, and mesenchymopathies. PIPO presents with abdominal distension, bilious vomiting, and severe constipation. Diagnosis is based on objective measures of neuromuscular dysfunction, dilated bowel on imaging, parenteral and/or enteral nutrition dependence, and genetic or metabolic testing. Antroduodenal manometry permits objective assessment of proximal bowel neuromuscular function. Genetic testing is increasingly valuable although causes of PIPO often remain incompletely defined. Understanding genotype‐phenotype correlations is essential for clarifying disease mechanisms and guiding therapies. This study aimed to characterize the clinical and genetic profiles of children with PIPO, utilizing manometric data for subtype classification.

A retrospective chart review was conducted at a tertiary care pediatric medical center, with inclusion criteria of PIPO diagnosis, completed manometry testing, and genetic evaluation.

Nineteen children met inclusion criteria. Antroduodenal manometry classified 59% as neuropathic, 35% as myopathic, and one with mixed neuropathic and myopathic dysfunction. Genetic testing revealed pathogenic ACTG2 mutations in all myopathic cases, while neuropathic PIPO exhibited more genetic variability. Histopathology was inconsistent and often nonspecific. Therapeutic approaches focused on nutritional support and promotility agents, with surgical intervention more common in myopathic cases.

This study highlights the association of ACTG2 mutations with a myopathic phenotype, and genetic diversity in neuropathic PIPO, emphasizing the need for further research to improve phenotyping to enhance diagnosis and treatment.

Pediatric intestinal pseudo‐obstruction (PIPO) is a life‐threatening bowel motility disorder with significant morbidity.PIPO pathogenesis includes neuropathies, myopathies, and mesenchymopathies, with genetic testing facilitating some diagnoses.
ACTG2 mutations are the most common genetic cause of myopathic PIPO, characterized by distinct manometric patterns in bowel, bladder and uterine dysfunction, and often intestinal malrotation.

Pediatric intestinal pseudo‐obstruction (PIPO) is a life‐threatening bowel motility disorder with significant morbidity.

PIPO pathogenesis includes neuropathies, myopathies, and mesenchymopathies, with genetic testing facilitating some diagnoses.

ACTG2 mutations are the most common genetic cause of myopathic PIPO, characterized by distinct manometric patterns in bowel, bladder and uterine dysfunction, and often intestinal malrotation.

The data suggest genetic variability in neuropathic PIPO, with fewer known disease‐causing variants compared to myopathic PIPO.Histopathological findings in patients with PIPO are inconsistent and nonspecific.Successful therapeutic approaches for PIPO subtypes differ, with surgical interventions more common in myopathic cases.

The data suggest genetic variability in neuropathic PIPO, with fewer known disease‐causing variants compared to myopathic PIPO.

Histopathological findings in patients with PIPO are inconsistent and nonspecific.

Successful therapeutic approaches for PIPO subtypes differ, with surgical interventions more common in myopathic cases.