Holt-Oram syndrome, also called a right-hand syndrome, is a genetic condition characterized by upper limb and heart defects. This is also known as an atrio-digital syndrome, atriodigital dysplasia, heart-limbing syndrome, ventriculo-radial syndrome. It is an autosomal dominant condition, which affects the arms and hands of the bones and also causes heart attacks.

CAUSES

Holt-Oram syndrome is an autosomal dominant genetic disorder that can be inherited. The TBX5 gene currently contains more than 70 known mutations that cause Holt-Oram syndrome. Potential triggers for the majority of the individuals affected include inadequate reading and translation of the TBX5 gene during protein development.

PATHOPHYSIOLOGY

UPPER LIMB INVOLVEMENT

Abnormalities may be asymmetric or unilateral and may include longitudinal, carpal, and thenar bones. Such bones are affected by aplasia, hypoplasia, fusion, or anomalous development with a variety with phenotypes, including triphalangeal or missing thumbs. Malformations or carpal bone fusions are the most prevalent findings in individuals with Holt-Oram syndrome. The only findings found in all affected individuals are carpal bone anomalies.

CARDIAC INVOLVEMENT

Around 75% of patients have any heart abnormality. The abnormality in most patients is either an atrial septal defect (ASD), or a ventricular septal defect (VSD), varying in number, scale, and location. Cardiac abnormalities can also include defects in cardiac conduction such as progressive atrioventricular blockage and atrial fibrillation.

SIGNS AND SYMPTOMS

UPPER LIMB DEFORMITY INCLUDES THE FOLLOWING FEATURES:

  • Always present but may be unilateral or bilateral
  • Left-sided abnormalities often more severe than a 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 the 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

TREATMENT

No drugs are effective in treating patients with Holt-Oram syndrome with anatomical deficiencies. It can be used to prophylaxis antibiotics. Patients with pulmonary hypertension should be found to be anticoagulant. Patients with atrial fibrillation should suggest cardioversion, antiarrhythmic drug treatment, or anticoagulation.

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