Holt-Oram Syndrome Clinical Presentation

Updated: Oct 14, 2022
  • Author: Craig T Basson, MD, PhD; Chief Editor: Yasmine S Ali, MD, MSCI, FACC, FACP  more...
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History and Physical Examination


Patients may have a family history of cardiac and/or limb malformation.

Patients may present in infancy with obvious limb malformations and/or signs of cardiac failure secondary to atrial septal defect (ASD), ventricular septal defect (VSD), or cardiac conduction disease.

Physical examination

Upper limb deformity includes the following features:

  • Always present but may be unilateral or bilateral

  • Left-sided abnormalities often more severe than right arm or hand abnormalities

  • Unequal arm lengths due to aplasia, hypoplasia, fusion, or anomalous development of the radial, carpal, and thenar bones

  • Abnormal forearm pronation and supination

  • Triphalangeal or absent thumbs

  • Possible abnormal opposition of thumb

  • Possible sloping shoulders and restriction of shoulder joint movement

  • Phocomelia

Cardiac involvement includes the following signs:

  • Bradycardia

  • Irregular pulse (ectopy)

  • Irregular pulse that occurs irregularly (atrial fibrillation)

  • Wide, fixed splitting of the second heart sound

  • Pulmonary systolic flow murmur

  • Holosystolic murmur (should raise consideration for a VSD)

Anomalies involving any of the following are indicators that a diagnosis of Holt-Oram syndrome can be excluded:

  • Ulnar bone

  • Lower limbs

  • Kidneys

  • Eyes

  • Auditory

  • Craniofacial

  • Vertebrae (may or may not occur in Holt-Oram syndrome)