Holt-Oram syndrome

Holt-Oram syndrome


Holt-Oram syndrome, also known as cardiomelic syndrome, is a syndrome with skeletal and cardiac abnormalities. It is an autosomal dominant condition, characterised by complete penetrance but variable expression of both cardiac and skeletal defects. There is no correlation between severity of cardiac and skeletal anomalies.


Skeletal abnormalities range from severe phocomelia to minor abnormalities such as clinodactyly and deformity of the carpal bones. Skeletal anomalies include triphalangeal, hypoplastic or absent thumb; syndactyly of the hands; absence of the first metacarpal; fifth finger clinodactyly; extra or deformed carpals; partial or complete absence or synostosis of the radius and ulna; deformation of the scapula, clavicle, and head of the humerus; and deformation of the sternum. There is often asymmetry of the skeletal abnormalities. The commonest cardiac abnormalities are atrial septal defect, which may be associated with arrhythmia, and ventricular septal defect. About one third of patients have other cardiac defects including patent ductus arteriosus, pulmonary stenosis, anomalous pulmonary venous drainage and conduction defects.

Differential Diagnosis

Trisomy 13, 18 may have upper limb deformities in association with cardiac defects. VATER/VACTERL association also has radial ray defects and may have cardiac anomalies, but there are generally also tracheo-oesphageal fistula and renal anomalies in this condition. Fanconi anaemia has medial aplasia or hypoplasia as well as associated thumb anomalies (unlike thrombocytopenia absent radius syndrome where the thumbs are normal). Other features that may be present on antenatal ultrasound include microcephaly and renal anomalies. Thrombocytopenia absent radius (TAR) also has radial defects and cardiac anomalies may be associated (in 30% of cases). However there is thrombocytopenia which is not seen in Holt-Oram syndrome.

Sonographic Features

Skeletal-Phocomelia – Absent carpals/metacarpals 

Digital syndactyly

Polydactyly – very unusual 

Growth discrepancy of upper limb bones (often asymmetric)




Pulmonary stenosis

Associated Syndromes

  • None


  1. Brons JTJ, van Geijn HP, Wladimiroff JW, et al Prenatal ultrasonographic diagnosis of the Holt-Oram syndrome Prenat Diagnosis 8:175-181
  2. Muller LM, de Jong G, van Heerden KMM The antenatal ultrasonographic detection of the Holt-Oram syndrome S Afr Med J 68:313-315
  3. Lehner R, Wenzl R, Vanura H, et al Diagnosis of familial Holt-Oram syndrome (German) Prenatal Diagn 8:175-181