HOLT-ORAM SYNDROME - A CLINICAL GENETIC-STUDY

A clinical and genetic study of the Holt-Oram syndrome (HOS) has been carried out in the United Kingdom involving 55 cases designated Holt-G ram syndrome, together with their parents and sibs. Data from the clin ical assessment of both familial and isolated cases were used to defin e the HOS phenotype and to outline the spectrum of abnormalities, espe cially factors affecting severity. Skeletal defects affected the upper limbs exclusively and were bilateral and asymmetrical. They ranged fr om minor signs such as clino-dactyly, Limited supination, and sloping shoulders to severe reduction deformities of the upper arm (4.5%). The radial ray was predominantly affected and the left side was more seve rely affected than the right. All affected cases showed evidence of up per limb involvement. Cardiac defects were seen in 95% of familial cas es and included both atrial septal defect (ASD, 34%) and ventricular s eptal defect (VSD, 25%); 39% had only ECG changes. Cardiac involvement ranged from asymptomatic conduction disturbances to multiple structur al defects requiring surgery in infancy. Sudden death could be caused by heart block. Inheritance was autosomal dominant with 100% penetranc e and no evidence of reduced fitness. Increasing severity occurred in succeeding generations consistent with anticipation.