Reversible bilateral sensorineural hearing loss associated with atorvastatin: a case report.

Gastrointestinal (GI) dysfunction is a prevalent comorbidity in individuals with neurodevelopmental disorders, including autism spectrum disorders (ASD), significantly affecting the quality of life [–]. ASD, characterized by deficits in social communication, restricted interests, and repetitive behaviours, affects approximately one in 36 children aged 8 years in the USA in 2020 []. Genetic factors play a major role in its pathogenesis, with various susceptibility genes and chromosomal abnormalities implicated. In addition to core features, individuals with ASD often experience GI issues, such as constipation, diarrhea, and abdominal pain, affecting up to 48–90% of individuals [, ]. The impact of GI dysfunction in ASD extends beyond physical discomfort; it can significantly impair quality of life, disrupt sleep patterns, interfere with educational and therapeutic interventions, and potentially exacerbate behavioural challenges such as irritability and aggression []. 15q duplication syndrome (Dup15q), a genetic subtype of ASD resulting from duplication of the 15q11.2-q13 chromosomal region, provides a valuable model for investigating the interplay between ASD, GI dysfunction, and behaviour. Dup15q is one of the most common genetic causes of ASD, accounting for up to 0.5–3% of cases []. Individuals with Dup15q frequently exhibit core ASD features as well as a high prevalence of GI issues, with constipation being a particularly common complaint presented in up to 60% of the patients surveyed [, ]. Clinical observations in Dup15q suggest a potential link between GI dysfunction and behavioural challenges, with improvements in irritability and aggression, and report following successful treatment of GI symptoms []. Studying GI dysfunction in Dup15q is important, as research shows 49% of children with Dup15q experience GI symptoms before diagnosis []. The enteric nervous system (ENS) plays a crucial role in regulating GI motility and function []. Enteric neurons express gamma-aminobutyric acid (GABA) and serotonin (5-hydroxytryptamine, 5-HT); however, they account for less than 5–1% respectively in mice [–]. Recent evidence indicates that endogenous 5-HT plays a limited role in generating major motor patterns such as colonic motor complexes (CMCs) [–]. Studies have shown that depletion of mucosal 5-HT through TPH1 knockout or removal of neuronal 5-HT does not impair colonic motility or transit in vivo [, ]. Nevertheless, 5-HT receptors remain widely expressed in the gut, and both agonists and antagonists can modulate motility, likely via constitutively active receptor mechanisms or ENS-independent pathways [, ]. Hence, while endogenous 5-HT may not be essential for gut motor coordination, pharmacological activation of 5-HT receptors can still influence gastrointestinal motility.