In Down syndrome (DS) constipation is common, and the incidence of Hirschsprung disease (HD) is 1-2%. Rectal suction biopsies (RSBs) in DS may show discordant features; calretinin immunoreactivity (CRir) often helps resolve discrepancies. We report a case of unequivocal very short-segment HD (vsHD) in an infant with DS who had aganglionosis with abnormal acetylcholine esterase (AChE) activity in 3 RSBs. The CRir patterns were scanty positive rather than the expected absent CRir innervation in the lamina propria (LP). The resection specimen was grossly typical for short-segment HD, with a 5.5-cm, narrow but normally ganglionated segment proximal to the verified very short distal anganglionic zone. Unequivocal calretinin hypoinnervation was limited to the distal 2 cm, substantiating the warning of Kapur that small numbers of CRir nerves in the LP do not exclude a diagnosis of vsHD. We evaluated RSBs from 11 DS and 20 randomly selected normal infants <6 months of age with chronic constipation. The normal infants had abundant mucosal calretinin innervation and AChE histochemistry. We observed variable CRir hypoinnervation in RSBs in DS infants (including 6/7 with "normal" original diagnosis and 1/4 with HD). Our findings caution against overdependence on "normal" calretinin immunohistochemistry and suggest that AChE may be more reliable than CRir in the context of DS. An unknown number of patients with DS may have enteric nervous system disorders functionally similar to HD, which are possibly related to abnormal or imbalanced autonomic innervation, of which distal calretinin hypoinnervation is one manifestation, despite the presence of ganglia.
Keywords: Down syndrome; Hirschsprung disease; calretinin; rectal biopsy.