October 1979 538 The Journal of P E D I A T R I C S Holt-Oram syndrome The autosomal dominant association of upper extremity skeletal defects with congenital heart disease is known as the Holt-Oram syndrome. We reviewed our experience with 39 affected patients of whom 15 were considered new mutations. Wide varieties of skeletal defects and congenital heart disease were observed, and the severity of skeletal involvement did not parallel that of cardiac disease. These patients demonstrate four previously unemphasized points: (1) There is a striking asymmetry of skeletal involvement, with the left side more severely affected. (2) Patients with skeletal defects alone can transmit both skeletal and cardiac defects to their children. (3) Hypoplastic peripheral vessels may be an associated abnormality and can result in difficulty with cardiac catheterization. (4) Electrocardiographic changes of terminal conduction delay in the right anterior chest leads' were not uniformly present in patients with otherwise typical secundum atrial septal defects. Ann T. Smith, M.D., George H. Sack, Jr., M.D., Ph.D.,* and George J. Taylor, M.D., Baltimore, Md. IN 1960, Holt and Oram I described a family in which upper extremity malformations were associated with secundum atrial septal defect. The subsequent literature (about 130 patients in either case reports or family studies) has demonstrated autosomal dominant transmis- sion of this syndrome with variable expression of skeletal and cardiac defects. The associated finding of hypoplastic peripheral vessels has not been noted again since the original report of Holt and Oram. We have reviewed the records of 39 patients with the Holt-Oram syndrome seen at the Johns Hopkins Hospital over 25 years. Fifteen patients had no family history of HOS. We observed a previously unemphasized asymme- try of skeletal involvement, with the left side more severely affected. Some patients had hypoplastic periph- eral vessels, which may constitute an increased risk for cardiac catheterization. From the Department of Medicine, Divisions of Internal Medicine and Medical Genetics, and the Department of Pediatrics, Johns Hopkins University School of Medicine. Clinical studies supported by United States Public Health Service Grant 1 T32 GM07471. Dr. Sack supported in part by the Andrew Mellon Foundation and United States Public Health Service Gra~it 1 RO1 CA Z0619-O1. ~: *Reprint address: The Moore Clinic, Division of Medical Genetics, The Johns Hopkins Hospital, Baltimore, MD 21205. METHODS The records of 22 patients with HOS followed in the Moore Genetics Clinic were reviewed, and five of these patients were re-examined. Records of an additional 17 patients were obtained from the Helen B. Taussig chil- dren's Cardiac Center. Abbreviations used HOS: Holt-Oram syndrome CHD: congenital heart disease, ASD: atrial septal defect ECG: electrocardiogram Patients with a negative family history (neither cardiac nor skeletal defects in siblings, parents, or grandparents) were included if both congenital heart disease and typical skeletal anomalies were present. Patients with a positive family history were included if they had cardiac and upper extremity anomalies or if they had typical skeletal defects alone. No family members had CHD without skeletal anomalies. Our study included 14 males and 25 females. Fifteen were black and 24 were white. Preoperative electrocardiograms on patients not receiv- ing digitalis were evaluated in 35 patients. Anatomic cardiac defects were identified on the basis of surgical or autopsy findings in 16 patients; 11 additional patients had their cardiac diagnosis established by cardiac catheteriza- tion. In eight patients the diagnosis of CHD was made by physical examination and noninvasive laboratory studies 2 Vol. 95, No. 4, pp. 538-543 0022-3476/79/100538 + 06500.60/0 9 1979 The C. V. Mosby Co.