Unusual Inconsolable Crying: An Insight, Case Report, and Review of the Literature on the Pitt-Hopkins Gastrointestinal Phenotype

Abstract

Pitt-Hopkins syndrome (PTHS) is a rare, neurodevelopmental genetic disorder caused by mutations in the TCF4 gene. This gene encodes a ubiquitous, class I, basic helix-loop-helix factor, which is implicated in various developmental and regulatory processes. Predominant clinical manifestations of PTHS include facial dysmorphisms, intellectual disability, absence of expressive language, epilepsy, as well as visual and musculoskeletal impairments. Gastrointestinal (GI) complications, such as chronic intestinal pseudo-obstruction, gastroparesis with delayed bowel transit, chronic constipation culminating in failure to thrive, and gastroesophageal reflux disease (GERD), are also prevalent in these patients. The early identification of pain etiology in PTHS patients poses a significant clinical challenge. This report presents two cases of PTHS patients suffering from gastrointestinal dysmotility, evaluated at our Pediatrics Clinic at the "Microcitemico" Hospital. A review of existing literature was conducted via the PubMed database to elucidate the current understanding of the GI phenotype in PTHS. Twenty articles were deemed most relevant and selected for this purpose. In both patients, severe constipation and abdominal distension resulted in persistent agitation and inconsolable crying. These distress symptoms were completely ameliorated following prompt pharmacological intervention.

Keywords: abdominal pain; gastrointestinal obstruction; inconsolable crying; pathogenic variant; pitt-hopkins syndrome; pseudo-obstruction; unusual cause of abdominal pain.