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(Circulation. 2000;101:e191.)
© 2000 American Heart Association, Inc.

Circulation Electronic Pages

Holt-Oram Syndrome vs Heart-Hand Syndrome

Craig T. Basson, MD, PhD

Director of Molecular Cardiology Weill Medical College of Cornell University, New York, NY

	Introduction

 
To the Editor:

In a recent article, Brockhoff et al¹ provide an elegant example of a patient affected by a heart-hand syndrome. Their findings also highlight the importance of modern cardiovascular genetics in clinical diagnosis. Although the patient presented certainly has both a cardiac septation defect and an upper limb deformity, recent DNA-based studies have demonstrated that the hand abnormalities shown would actually make a diagnosis of Holt-Oram syndrome unlikely.

Heart-hand syndromes are a broad category of disease, of which Holt-Oram syndrome is the most common form. Other heart-hand syndromes (reviewed in Reference 2) include Tabatznik’s syndrome and heart-hand syndrome type III. Holt-Oram syndrome can be distinguished from these syndromes by its primary limb abnormality: upper limb deformity in the preaxial radial ray distribution.³ Individuals with other heart-hand syndromes, including the patient described by Brockhoff et al, may have primary upper limb malformation in the postaxial ulnar ray distribution and can even have a lower limb deformity. Our previous studies² have demonstrated that the class of disorders referred to as heart-hand syndromes is genetically heterogeneous and that only Holt-Oram syndrome^{4 5} is due to mutations in the TBX5 transcription factor gene at human chromosome 12q24.1.

Although it would be technically feasible to screen DNA samples from Brockhoff et al’s patient for the TBX5 mutations that cause Holt-Oram syndrome, the absence of upper limb radial ray abnormalities suggests that such a search is unlikely to be fruitful. Diagnostic precision in heritable heart-hand syndromes is essential for the informed clinical evaluation of other . . . [Full Text of this Article]

Thomas Münzel, MD; Carsten Brockhoff, MD; Henning Kober, MD; Nikos Tsilimingas, MD; Friedhelm Dapper, MD; Thomas Meinertz, MD

Departments of Cardiology and Cardiac Surgery, University Hospital Eppendorf, Hamburg, Germany