Abstract 426 Poster Session IV, Tuesday, 5/4 (poster 200)

Disturbances of left-right asymmetry (i.e. laterality defects) such as asplenia and polysplenia are observed in approximately 1/10,000 livebirths. Many children with these laterality defects also have complex congenital heart malformations. Furthermore, reports have suggested that a variety of defects of the midline can also be observed in children with laterality defects.

We have collected phenotypic data from 67 probands with laterality defects and congenital heart disease. This includes 10 potential families with multiple affected members. A number of these children also exhibit birth defects of midline structures. These include scoliosis, tracheoesophageal fistula/esophageal atresia, caudal dysgenesis associated with maternal diabetes, bony defects, polycystic kidney, omphalocele, cleft palate, anal atresia, sirenomelia sequence with anencephaly, hypospadius, and sacral duplication.

These findings suggest that the development of the midline and of left-right asymmetry are connected. Studies of left-right axis determination in model organisms such as frog, zebrafish, and mouse have also identified this association. This correlation should alert clinicians to look for laterality defects when evaluating children with anomalies of the midline, and will foster a more accurate phenotypic assessment of families with laterality defects. A critical understanding of the phenotypes associated with laterality defects is a prerequisite for identifying the molecular basis of laterality disorders in humans.