Holt-Oram Syndrome

Genetically transmitted malformation syndrome characterized by congenital thenar hypoplasia and the association of a congenital heart disease (ventricular and atrial septal defect) and upper limb malformation (underdevelopment of bones and/or extra bones).

Atriodigital Dysplasia; Cardiac-Limb Syndrome; HOS; Heart-Hand Syndrome, Holt-Oram Type.

Congenital disorder of digital and/or radial dysostosis associated with congenital heart disease. First described in 1960 by Holt and Oram in a four-generation family with atrial septal defects and thumb abnormalities.

Prevalence estimated at 0.95:100,000 live births. More than 50% of cases are caused by new mutations (no parental inheritance).

Autosomal dominant, variable expression but strong penetrance (90-100%). Mutation of the long arm of chromosome 12 (12q24.1). No sex predilection.

Holt-Oram syndrome is caused by mutations in the transcription factor TBX5, which is critical for development of the heart and upper limbs. No contributory environmental factors are known. A number of syndromes phenotypically resemble Holt-Oram syndrome but arise from different mutations.

Absent, bifid, hypoplastic, or triphalangeal thumb associated with cardiac septation defects, classically atrial septal defect (often with conduction defects) but also ventricular septal defect.

As well as dysostosis of the thumb, the Holt-Oram syndrome may be associated with radial dysgenesis. Clinical presentation depends on the severity of cardiac disease (atrial septal defect in 70% of cases) but may include severe endocardial cushion defects, mitral valve prolapse, and hypoplastic left heart syndrome.

An anesthesiology consultation is recommended before elective surgery. Obtain a history and examine for signs and symptoms suggestive of ventricular failure and cyanosis. Perform an electrocardiogram (ECG) and echocardiography to define cardiac anatomy. Cardiac catheterization may be indicated for complex lesions.

The anesthetic technique is dictated by the presence of cardiac disease. Consider premedication, use measures to limit increases in pulmonary artery pressure (prevent hypercarbia, maintain PaO2). If the pulmonary and systemic circulations are in parallel as in the hypoplastic left heart syndrome, strict attention must be paid to maintaining the balance of flow to the pulmonary and systemic vascular beds, primarily by manipulating pulmonary vascular resistance.

No specific drug contraindications other than those dictated by individual cardiac lesions. Antibiotic prophylaxis of endocarditis is recommended.

Aase Syndrome: Autosomal recessive syndrome characterized by bilateral triphalangeal thumbs, radial hypoplasia, congenital hypoplastic anemia, joint and skeletal deformities, delayed fontanelle closures, poor peripheral vascular access, possible ventricular septal defect.

Cavanagh Syndrome: Rare anomaly of the upper extremities that presents with unilateral or bilateral hypoplasia of the thenar eminence. Typical clinical, radiographic, and electrophysiologic findings emphasize the diagnosis. Differentiation from carpal tunnel syndrome is important to prevent unnecessary surgical intervention. Electrophysiologic and radiographic findings are necessary tools to establish a correct diagnosis.

Haas Malformation: Congenital thenar hypoplasia associated with hand anomaly defined as complete and bilateral syndactyly, marked by six metacarpals and digits and fingers flexion. Autosomal dominant inheritance.

Okihiro Syndrome (Duane-Radial Ray Syndrome): Autosomal dominant malformation characterized by radial anomalies of the upper extremities with a Duane anomaly (nerve abducens paresis of the ipsilateral lateral rectus muscle of the eye). Other features include congenital heart defects, vascular anomalies, dysplastic ears, hearing loss, and renal anomalies. Thenar hypoplasia.

TAR Syndrome (Thrombocytopenia, Absent Radius): Characterized by severe bleeding episodes during infancy. Other features include aplasia of the thumb (radii) and hypoplasia ulnae. Congenital heart and renal defects, mental retardation secondary to brain hemorrhages. Inherited as autosomal recessive trait.

Va(C)Ter(L) Association: Acronym for vertebral anomalies, anal atresia, (cardiac defects), tracheo-esophageal fistula, renal (and limb anomalies). The name describes the most important defects of this disorder. The diagnosis usually is made based on the presence of three of the characteristic findings.