Gastrointestinal phenotype of ATR‐X syndrome

Abstract

X-linked alpha thalassemia mental retardation (ATR-X) syndrome is associated with profound developmental delay, facial dysmorphism, genital abnormalities, and alpha thalassemia. Patients with ATR-X syndrome frequently present with gastrointestinal problems, in particular feeding difficulties, regurgitation and vomiting, abdominal pain, distension, and chronic constipation. Parental reports of prolonged food refusal and distress in these children are common and although these episodes are suspected to be gastro-intestinal in origin they are rarely investigated. Death in early childhood from aspiration of vomitus or from pneumonia presumed to be secondary to aspiration has been recorded in a number of ATR-X cases. In this report we review the gastrointestinal phenotype of ATR-X syndrome in 128 cases. We also demonstrate that in two siblings, regurgitation was secondary to gastric pseudo-volvulus, a condition in which the stomach does not have a normal system of peritoneal ligaments and changes position with possible torsion around itself. Furthermore, ultra-short Hirschsprung disease with colonic hypoganglionosis was shown and this may contribute to the severe constipation affecting these children.

Esophago‐gastric motility and nutritional management in a child with ATR‐X syndrome

“…The gastrointestinal phenotype of these patients includes diverse symptoms. According to analysis of 128 children with ATR‐X syndrome, drooling (36%), GER (72%) and constipation (30%) have been described as the three major symptoms, as was the case with the present patient . Moreover, some children suffered from upper gastrointestinal bleeding, aspiration of vomitus, intestinal malrotation, ileus, or pseudo‐obstruction, and some of them died with these conditions .…”

“…Laparoscopic fundoplication and tailored indication of gastrostomy have become the standard procedure in neurologically impaired children . Although certain patients with ATR‐X syndrome underwent fundoplication (10%) and gastrostomy (9%), rash judgment to carry out fundoplication in those patients with GER who have poor esophageal clearance may worsen vomiting or disturb oral intake. Given that the present patient had slow esophageal clearance, we chose laparoscopic correction of gastric volvulus combined with button PEG‐J placement.…”

“…Mutations in the ATRX gene locus Xq13.3 were first described in 1995, and, to date, a number of mutations have been identified in patients with ATR‐X syndrome . Gastrointestinal symptoms such as feeding difficulties, regurgitation, abdominal distention and chronic constipation have been recognized as common complications . Given that aspiration pneumonia related to gastroesophageal reflux (GER) has been identified as the major cause of death in these patients, investigation of gastrointestinal abnormalities is considered to reduce mortality and morbidity.…”

Coordinated Regulation of Intestinal Functions in C. elegans by LIN-35/Rb and SLR-2

“…This latter finding is also consistent with an absence of cell cycle genes from the slr-2 regulon (Figure 3; Figure S6). Interestingly, the human ortholog of another lin-35 -synthetic gene identified by our screen, xnp-1 /ATR-X, was recently implicated in intestinal functions, as mutations in ATR-X led to a wide range of gastrointestinal abnormalities [60].…”

Perspectives in Pediatric Pathology, Chapter 6. Male Undermasculinization

“…Death in early childhood occurs from aspiration of vomitus or from pneumonia presumed to be secondary to aspiration. This has been recorded in a number of ATR-X cases [255]. Hemoglobin H inclusions in the red blood cells are characteristic of this syndrome [256].…”