Extracardiac anomalies in the heterotaxy syndromes with focus on anomaliesof midline-associated structures

The extracardiac defects in patients with heterotaxy have not been examined as extensively as cardiac defects. We found a high incidence of midline-as sociated defects in 160 autopsied cases of heterotaxy (asplenia, polyspleni a, or single right-sided spleen). Fifty-two percent of patients with left-s ided polysplenia had a midline-associated defect, as did 45% of those with asplenia, Most common were musculoskeletal or genitourinary anomalies, as w ell as cleft palate. Fused adrenal glands and anal stenosis or atresia occu rred exclusively among patients with asplenia, A midline anomaly was twice as likely to be detected on complete autopsy than from clinical findings al one. Linkage studies should take into account that affected subjects may ha ve isolated subclinical midline defects. The high incidence of midline-asso ciated defects supports the theory that the midline plays a critical role i n establishing left-right asymmetry in the body. Comparison of these defect s with mouse models of laterality defects suggests that mutations that disr upt the transforming growth factor beta pathway may result in heterotaxy, ( C)2000 by Excerpta Medica, Inc.