Pedigree analysis and descriptive investigation of three classic phenotypes associated with Holt-Oram syndrome.

OBJECTIVE: To determine the frequency of sporadic and familial cases of three classic phenotypes associated with Holt-Oran syndrome (HOS).

STUDY DESIGN: We determined the frequency of sporadic and familial cases based on the 179 patients with HOS reported in the literature.

RESULTS: Clinically, there are three variations of HOS: affected individuals may have only skeletal anomalies (27.4%), only cardiac defects (3.9%) or both (68.7%). Of the 179 affected individuals, 17.3% had sporadic and 82.7% had familial disease.

CONCLUSION: The equal distribution between the sexes (female 53%, male 47%) indicates that HOS is transmitted as an autosomal dominant trait. In contrast to familial cases, cardiac involvement alone was not reported in any of the sporadic cases. When a cardiac malformation is diagnosed, the family members of the affected individual should be carefully screened for Holt-Oram syndrome.