Holt-Oram Syndrome

Saquib Khawar M.D.

Northwestern University

Daniel Schwartz M.D.

Children's Memorial Hospital

Abstract

Neonate with multiple VSD's.

Keywords

1425 Holt-Oram syndrome congenital heart defects limb anomalies


Publication Date: 2008-05-07

History

Neonate with multiple VSD's. (Click on "original size" button for better quality images.)

Findings

Image 1. Both clavicles with bulbous ends and upward inclination of the clavicles, imparting a characteristic ‘handle bar’ configuration to the bones. No other bony abnormality including of the spine and thorax.

Images 2&3. Bilateral proximal radio-ulnar synostosis.

Images 4&5. Bilaterally only 4 triphalangeal digitsabsent thumbs.

Images 6.7,8&9. Normal lower limbs.

Diagnosis

Holt–Oram syndrome (HOS)

Synonyms: Atriodigital syndrome, Heart hand syndrome.

DDx

None.

(Note that handle bar clavicles have also been associated with other syndromes like Diastrophic dysplasia, Osteodysplastia, thrombocytopenia absent radius syndrome, Trisomy 18 however they each have their characteristic constellation of associated findings.)

Discussion

Holt- Oram syndrome (HOS) is characterized by mild-severe congenital cardiac defects and skeletal abnormalities of the upper limbs. Incidence is 1 in 100000 live births. HOS is an autosomal dominant trait with complete penetrance. Underlying genetic defect is on the long arm of chromosome 12 (12q2), with mutatations in the TBX3 and TBX5 genes leading to a wide range of phenotypes.

Musculoskeletal defects involve the upper limbs bilaterally, with the left side often more significantly affected. Defects range from most severe with phocomelia with rudimentary limbs to mild such as clinodactyly (5th digit curving towards the 4th), limited supination and sloping shoulders. Most common defects include radial ray anomalies ranging from absent to displaced, duplicated or triphalangeal thumbs. Carpal defects may be present. Sprengel deformity of the scapula, hyoplasia of the shoulders, clavicles (‘handle bar’) and humerus have been reported. There may be associated muscular hypoplasia

Congenital cardiac defects are seen in ~75% of pts. The most common is secundum ASD followed by VSD and primum ASD. Others include various degrees of AV block, pulmonic stenosis and more complex defects such as Tetralogy, hypoplastic left heart, truncus arteriosus, endocardial cushion defects, anomalies of the vena cava, subclavian artery and coarctation and hypoplastic aortic arch among others.

Genetic counseling is recommended.

References

  1. 1. Bossert T, Walther T, GummertJ, et al. Holt Oram syndrome. Orphanet Encyclopedia, April 2003.
  2. 2. Basson CT, Cowle GS, Solomon SD et al. The clinical and genetic spectrum of the Holt Oram syndrome (heart-hand syndrome). N Engl J Med Mar 31 1994;330(13):885-91.

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