Potential role of pyridostigmine in the management of pediatric chronic intestinal pseudo-obstruction in a girl with ACTL6B mutation: a case report and a review of literature.

BACKGROUND: Mutations in the ACTL6B gene are implicated in a wide range of neurodevelopmental disorders, such as global developmental delay, drug-resistant epilepsy, aphasia, autistic traits, dystonia, and cerebral malformations. Recessive variants are typically associated with severe phenotypes, while dominant mutations lead to moderate-to-severe clinical presentations. Although neurological involvement is well characterized, gastrointestinal manifestations, particularly motility disorders, have not been previously associated with ACTL6B-related disease. Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare, severe gastrointestinal dysmotility disorder. Pyridostigmine, an acetylcholinesterase inhibitor with prokinetic effects, has recently been used off-label in selected PIPO cases.

METHODS: We present the clinical course of a 9-year-old female patient with a confirmed pathogenic ACTL6B mutation and a severe neurodevelopmental phenotype. Following persistent feeding intolerance and failure to thrive, the patient underwent surgical intervention, which did not result in significant clinical improvement. Given the suspected neuropathic component of the gastrointestinal dysmotility, pyridostigmine therapy was initiated.

RESULTS: The introduction of pyridostigmine led to improved enteral feeding tolerance, a marked reduction in vomiting episodes, and stabilization of nutritional status, suggesting a potential benefit in managing gastrointestinal symptoms in this patient population.

CONCLUSIONS: This case suggests a possible link between ACTL6B-related neurodevelopmental disorders and gastrointestinal dysmotility; if confirmed, it could expand the known clinical spectrum of the disease. Pyridostigmine could be considered as adjunctive therapy in PIPO, especially when a neuropathic etiology is suspected.