Holt-Oram Syndrome

The Holt-Oram syndrome is an autosomal dominant heritable disorder characterized by skeletal upper-limb dysplasias and congenital cardiac defects.

We describe a 43-year-old woman who presented with paroxysmal tachycardia and progressive heart failure. Both ring fingers were abnormally short as a result of dysplasia of metacarpal IV (Figure 1⇓). Auscultation revealed a loud systolic murmur at the left sternal margin and a widely split S₂. The ECG was consistent with right ventricular hypertrophy (Figure 2⇓). The chest x-ray showed severe right atrial and right ventricular dilatation and marked bilateral central pulmonary arterial distension with small peripheral pulmonary vessels (Figure 3⇓, left). Echocardiography showed a large secundum-type atrial septal defect with signs of severe right ventricular volume overload. At right heart catheterization, oximetry showed a large left-to-right shunt at the atrial level with a Qp/Qs ratio of 2.3. The mean pulmonary arterial pressure was 53 mm Hg, and the wedge pressure was 13 mm Hg. A pulmonary arteriolar resistance of 851 dyn · s · cm⁻⁵ was calculated. Operative closure of the atrial septal defect was undertaken despite markedly elevated pulmonary arteriolar resistance. Three months after the procedure, the patient reported excellent clinical improvement: there was no murmur, the size of the heart and the radiological signs of pulmonary hyperperfusion had decreased significantly (Figure 3⇓, right), pulmonary artery mean pressure was 14 mm Hg, and pulmonary arteriolar resistance had decreased to 412 dyn · s · cm⁻⁵.

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Figure 1.

Patient’s hands. Both ring fingers are abnormally short as a result of dysplasia of metacarpal IV.

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Figure 2.

ECG showing P pulmonale, right axis deviation, and qR pattern in V₁ and V₂, thus being compatible with right atrial and right ventricular hypertrophy.

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Figure 3.

Left, Chest x-ray before surgery. Right ventricle, right atrium, and central parts of pulmonary artery are massively enlarged. Right, Chest x-ray after operative closure of atrial septal defect, showing significant reduction of right atrial and right ventricular dimensions and of central pulmonary artery distension.

• Copyright © 1999 by American Heart Association