Rectal Biopsy in Children with down Syndrome and Chronic Constipation: Hirschsprung Disease vs Non-Hirschsprung Disease

Abstract

Hirschsprung disease (HD) is reported in patients with Down syndrome with a frequency between 2% and 10%. The incidence of HD is 2% in our community-based registry that contains >700 patients with Down syndrome. We reviewed rectal biopsy findings in 32 of these patients who had suction rectal biopsy performed between 1980 and 2009 to investigate the cause of chronic constipation. We confirmed that 15 patients had diagnostic histologic and histochemical features of HD. More challenging were findings in 5 of 17 patients, in whom ganglia coexisted with equivocal acetylcholinesterase reaction patterns and/or hypertrophic submucosal nerves. In this retrospective study, we were able to resolve most of these discrepant findings by demonstrating normal calretinin-positive nerve twigs in the lamina propria and muscularis mucosae. The clinical significance of these unexpected findings in suction rectal biopsy specimens that did not satisfy strict criteria for a tissue diagnosis of HD is unknown. We speculate that a minority of these patients have transition zone morphology or an incomplete/atypical form of HD. Further investigations may help resolve discrepancies that arise when suction rectal biopsy is used to investigate chronic constipation in Down syndrome.

Gastrointestinal disorders in Down syndrome

“…Constipation in DS is usually consequence of hypotonia, but in severe cases, short segment Hirchsprung disease should be excluded as well as hypothroidism and celiac disease (Malt et al, ; Maris et al, ). In a registry population of patients with DS 15/700 (2%) had suction rectal biopsy performed to investigate the cause of chronic constipation with diagnostic histologic and histochemical features of Hirchsprung disease (Yin, Boyd, Pacheco, Schonfeld, & Bove, ).…”

Calretinin, β‐Tubulin Immunohistochemistry, and Submucosal Nerve Trunks Morphology in Hirschsprung Disease

“…Although acetylcholinesterase (AchE) staining plays a key role, the need for frozen material and the related technical difficulties represent an intrinsic limit of this diagnostic tool (26). Calretinin immunohistochemistry does not require additional frozen material, as for AchE, and can be performed on the same paraffin-embedded tissue used for HE-stained sections for direct correlation (19)(20)(21)(22). suction rectal biopsies and demonstrated a higher diagnostic accuracy than AchE, with fewer errors and equivocal findings.…”

“…Among the different immunohistochemical markers, the calcium-binding protein calretinin appears to be a promising diagnostic tool in HD, although contrasting results have been reported, especially in challenging cases (18)(19)(20)(21)(22). Various antibodies recognizing different cytoskeleton proteins, such as microtubule-associated protein 2 (MAP-2) or b-tubulin, which are welldefined markers of neuronal differentiation in the central and peripheral nervous systems, have been also tested (23).…”

Prevalence of constipation in people with intellectual disability: A systematic review

“…Only one study employed a sample frame (general practices in the Netherlands) broadly representative of people with intellectual disability (Straetmans, van Schrojenstein Lantman-de Valk, Schellevis, & Dinant, 2007). A further six studies employed a sample broadly representative of people with intellectual disability from a particular subpopulation: Down syndrome (Alexander et al, 2015;Yin, Boyd, Pacheco, Schonfeld, & Bove, 2012), children with Down syndrome (Leonard, Bower, Petterson, & Leonard, 1999;Thomas et al, 2011), children with severe generalized cerebral palsy (Veugelers et al, 2010), and adults with ASD (Jones et al, 2015).…”

“…The rates presented for constipation in Table 1 range from 96.4% of people with profound intellectual disability living in an institution (Kozma & Mason, 2003) to 4.5% of people on a Down syndrome register with constipation of sufficient severity to warrant investigation for Hirschsprung's disease (HD) (Yin et al, 2012). The wide variation in the figures can be attributed to differences in the characteristics of the samples included, the definition of constipation used, and the method of ascertainment which has been found to be related to variation in prevalence estimates (Peppas et al, 2008;Suares & Ford, 2011).…”