Hirschsprung-like aganglionosis of the colon in patients with nail patella syndrome: Extension of the NPS phenotype to a fourth organ system. M.J. Wright, I. McIntosh. Greenberg Center for Skeletal Dysplasias & Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD.

   Nail patella syndrome (NPS) is a pleiotropic condition characterized by dysplasia of the nails, hypoplasia of the patellae, elbow dysplasia and progressive kidney disease. In addition, open-angle glaucoma has recently been shown to be part of the phenotype. The syndrome is inherited in an autosomal dominant manner and has been shown to result from mutations in the LIM-homeodomain encoding LMX1B gene. A number of individuals affected with NPS describe symptoms of severe constipation, often from birth, and often requiring medication. A proportion of these had been diagnosed with megacolon. Together these findings are suggestive of short-segment Hirschsprung disease. One 16 year old male with a history of constipation from birth, with failure to pass meconium until 2 weeks of age, presented with recurring fecal impaction. Barium enema demonstrated enlargement of the rectum and left colon consistent with the diagnosis of secondary megacolon. Transmural rectal biopsy performed at analrectal strip myomectomy showed aganglionosis and fibrosis of the muscularis propria confirming the diagnosis of aganglionic megacolon. Anecdotal evidence would suggest that aganglionic megacolon may be as common and as clinically significant among patients with NPS as kidney disease or glaucoma. Of interest, it has recently been shown that the C. elegans ortholog of LMX1B, lim-6, regulates the outgrowth and differentiation of neurons controlling rhythmic enteric muscle contractions. lim-6 mutant animals exhibit a bloated gut and defective defecation behavior. In conclusion, we suggest that assessment of individuals with NPS should include direct questioning regarding symptoms of constipation to allow definitive diagnosis of this treatable complication.