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Holt-Oram syndrome

S. Manohar, MD, DMRD., M. Mohan Karthikeyan, MD, DMRD., S.Vidya, MD, MBBS, DDVL

Article Published: Feb 16, 2010

India.

Case report

The following images show a case of Holt-Oram syndrom diagnosed at 27 weeks of gestation. Patient was a 27-year-old healthy G1 P0. There was non-contributive family history, non-consanguineous pregnancy, no exposure to teratogens.

We have seen the following findings during the ultrasound examination:

  • Ventricular septal defect
  • Absent radius of the left upper extremity
  • Absent thumbs on both upper extremities
  • Abnormal position of both hands

Parents decided for the pregnancy termination based on the ultrasound findings. Karyotyping was not performed due to financial cost. Parents didn't agree on the autopsy so there's no pathology report available.

Images 1,2: Image 1 shows normal fetal face and axial view of the fetal brain. Image 2 shows mild pyelectasis.

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Images 3,4: Images shows shortened left upper extremity with absent radius and abnormal rotation of the left hand.

 
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Images 5,6: Images show ventricular septal heart defect.

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Images 7,8: 3D images nicely demonstrating the abnormalities of upper extremities, left upper extremity is more severely affected than the right one.

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Images 9,10: Images of the left upper extremity, corresponding with the ultrasound findings.

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Images 11,12: Images show a fetus with affected upper extremities, note absence of the thumbs. Left extremity has absent radius, it's severely shortened.

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Holt_Oram_Manohar_12

Conclusion

Holt-Oram syndrome is characterized by:

  • Upper-extremity malformations (often more severe on the left side); carpal bone anomalies are always present; radial or thenar bones are usually involved, triphalangeal or absent thumb, radial ray aplasia, phocomelia, abnormal position of the hand.  
  • Personal/family history of congenital heart diesease (75 % of affected individuals have a congenital heart disease); most commonly: ostium secundum atrial septal defect, ventricular septal defect.  
  • Cardiac conduction defect; first-degree atrioventricular block which may progress into complete heart block.
Inheritance is autosomal dominant but the majority of cases are the result of de novo mutations . There is a 50 % chance that the offspring of the individual with Holt-Oram syndrome will be affected as well. There is a 100 % penetrance for the upper extremity anomalies. The severity of defects is increasing in successive generations (anticipation). In such a case, detailed prenatal ultrasound screening aimed at upper extremities and fetal heart is necessary. Molecular genetic testing is available, mutation in TBX5 is present in 70 % of cases of Holt-oram syndrome.

Differential diagnosis

Differential diagnosis includes: Fanconi anemia, Thrombocytopenia-absent radius syndrome (thumbs are always present), VACTERL, Heart-hand syndrome II, III, teratogen exposure (Thalidomide, Valproate) and trisomy 18.

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