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Thorac Cardiovasc Surg 2002; 50(5): 312-314
DOI: 10.1055/s-2002-34573
Review
© Georg Thieme Verlag Stuttgart · New York

Cardiac Malformations Associated with the Holt-Oram Syndrome - Report on a Family and Review of the Literature

T.  Bossert1 , T.  Walther1 , J.  Gummert1 , R.  Hubald1 , M.  Kostelka1 , F.  W.  Mohr1
  • 1Universität Leipzig, Herzzentrum, Klinik für Herzchirurgie, Germany
This paper was presented at the 3rd Joint Meeting of the German, Austrian and Swiss Societies for Thoracic and Cardiovascular Surgery in Lucerne, in February 2000
Further Information

Publication History

Received March 18, 2002

Publication Date:
08 October 2002 (online)

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Abstract

The Holt-Oram syndrome (HOS) is characterized by mild-to-severe congenital cardiac defects and skeletal abnormalities of the upper limb. The most common cardiac disorder is an ostium secundum atrial septal defect (ASD), followed by ventricular septal defect (VSD) and ostium primum ASD. Electrocardiographic abnormalities, such as various degrees of atrioventricular block, have also been reported. In addition, hypoplastic peripheral vessels of the upper limbs have been observed. Here, we will report about a family with three sons having HOS, and we will detail the cardiac spectrum of HOS as reported in the literature.

Key words

Holt-Oram syndrome - Congenital heart defects - Septal defects - Limb anomalies

References

  • 1 Holt M, Oram S. Familial heart disease with skeletal malformations.  Br Heart J. 1960;  22 236-242
    PubMedGoogle Scholar
  • 2 Starke H, Schimke R N, Dunn M. Upper limb cardiac syndrome: A family study.  Am J Cardiol. 1967;  19 588-592
    CrossrefPubMedGoogle Scholar
  • 3 Basson C T, Cowley G S, Solomon S D, Weissman B, Poznanski A K, Traill T A, Seidman J G, Seidman C E. The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome).  N Engl J Med. 1994;  330 885-891
    CrossrefPubMedGoogle Scholar
  • 4 Li Q Y, Newbury-Ecob R A, Terrett J A, Wilson D l, Curtis A R, Yi C H, Gebuhr T, Bullen P J, Robson S C, Strachan T, Bonnet D, Lyonnet S, Young I D, Raeburn J A, Buckler A J, Law D J, Brook J D. Holt-Oram syndrome is caused by mutations in TBXS, a member of the Brachyury (T) gene family.  Nat Genet. 1997;  15 21-29
    PubMedGoogle Scholar
  • 5 Basson C T, Bachinsky D R, Lin R C, Levi T, Elkins J A, Soults J, Grayzel D, Kroumpouzou E, Traill T A, Leblanc-Straceski J, Renault B, Kucherlapati R, Seidman J G, Seidman C E. Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome.  Nat Genet. 1997;  15 30-35
    PubMedGoogle Scholar
  • 6 Weber M, Wenz W, van Riel A, Kaufmann A, Graf J. Das Holt-Oram Syndrom (HOS). Literaturüberblick und aktuelle orthopädische Behandlungskonzepte [The Holt-Oram syndrome. Review of the literature and current orthopedic treatment concepts].  Z Orthop Ihre Grenzgeb. 1997;  135 368-375
    PubMedGoogle Scholar
  • 7 Newbury-Ecob R A, Leanage R, Raeburn J A, Young I D. Holt-Oram syndrome: a clinical genetic study.  J Med Genet. 1996;  33 300-307
    CrossrefPubMedGoogle Scholar
  • 8 Tucker K J, Murphy J, Conti J B, Curtis A B. Syncope and sinus arrest associated with the upper limb-cardiovascular (Holt-Oram) syndrome.  Pacing Clin Electrophysiol. 1994;  17 1678-1680
    PubMedGoogle Scholar
  • 9 Gaul G, Titscher G, Brand O, Heeger H. Bericht über eine Familie mit Holt-Oram-Syndrom.  Z Kardiol. 1979;  68 173-175
    PubMedGoogle Scholar
  • 10 Zhang K Z, Sun Q B, Cheng T O. Holt-Oram syndrome in China: a collective review of 18 cases.  Am Heart J. 1986;  111 572-577
    CrossrefPubMedGoogle Scholar
  • 11 Shono S, Higa K, Kumano K, Dan K. Holt-Oram syndrome.  Br J Anaesth. 1998;  80 856-857
    PubMedGoogle Scholar
  • 12 Sletten L J, Pierpont M E. Variation in severity of cardiac disease in Holt-Oram syndrome.  Am J Med Genet. 1996;  65 128-132
    CrossrefPubMedGoogle Scholar
  • 13 Cachat F, Rapatsalahy A, Sekarski N, Hurni M, von Segesser L, Payot M. Arch Mal.  Coeur Vaiss. 1999;  92 667-669
    PubMedGoogle Scholar
  • 14 Ito M, Misawa T, Fujino M, Ito S, Fukumoto T. A family of Holt-Oram syndrome.  Jpn Heart J. 1975;  16 480-487
    PubMedGoogle Scholar
  • 15 Bennhagen R G, Menahem S. Holt-Oram syndrome and multiple ventricular septal defects: an association suggesting a possible genetic marker?.  Cardiol Young. 1998;  8 128-130
    PubMedGoogle Scholar
  • 16 Kumar A, van Mierop L H, Epstein M L. Pathogenetic implications of muscular ventricular septal defect in Holt-Oram syndrome.  Am J Cardiol. 1994;  73 993-995
    CrossrefPubMedGoogle Scholar
  • 17 Di Luzio V, Blandini A, Ballerini L, Purcaro A. Association of the Holt-Oram syndrome (digito-atrial dysplasia) and mitral prolapse in a family.  G Ital Cardiol. 1981;  11 1548-1555
    PubMedGoogle Scholar
  • 18 Glauser T A, Zackai E, Weinberg P, Clancy R. Holt-Oram syndrome associated with the hypoplastic left heart syndrome.  Clin Genet. 1989;  36 69-72
    PubMedGoogle Scholar
  • 19 Holmes L B. Congenital heart disease and upper-extremity deformities.  N Engl J Med. 1965;  272 437
    PubMedGoogle Scholar
  • 20 Frontera-lzquierdo P, Cabezuelo-Huerta G. Severe Holt-Oram syndrome with pulmonary hypertension.  Am Heart J. 1991;  122 250-252
    CrossrefPubMedGoogle Scholar
  • 21 Del Corso L, Vannini A, De Marco S, Gnesi A, Pentimone F. Complete endocardial cushion defect and bone malformations of the hands. Holt-Oram sindrome.  Minerva Med. 1991;  82 683-686
    PubMedGoogle Scholar
  • 22 Lehner R, Wenzl R, Vanura H, Frank W, Safar P, Husslein P. Diagnose eines familiaren Holt-Oram Syndroms.  Z Geburtshilfe Perinatol. 1994;  198 143-149
    PubMedGoogle Scholar
  • 23 Massumi R A, Nutter D O. The syndrome of familial defects of heart and upper extremities (Holt-Oram syndrome).  Circulation. 1966;  34 65-76
    PubMedGoogle Scholar
  • 24 Ruzic B, Bosnar B, Beleznay O. Ein seltener Herzfehler als Symptom des Holt-Oram-Syndroms.  Radiologe. 1981;  21 296-299
    PubMedGoogle Scholar
  • 25 Solit R W, Smullens S N, Templeton J Y. Congenital heart disease and upper extremity defects. A case report (Holt-Oram syndrome).  J Cardiovasc Surg (Torino). 1973;  14 76-80
    PubMedGoogle Scholar
  • 26 Koishizawa T, Hayashi N, Tadokoro M, Nonaka T, Fujiki T, Fujikura T, Tonari K, Sasagawa N, Honda K, Ikeda K. A case report of the radical correction of a truncus arteriosus and peripheral pulmonary stenosis in association with Holt-Oram syndrome.  Kyobu Geka. 1995;  48 133-136
    PubMedGoogle Scholar
  • 27 Kullmann F, Koch R, Feichtinger W, Giesen H, Schmid M, Grimm T. Holt-Oram Syndrom in Kombination mit reziproker Translokation, Lungenhypoplasie und Kardiomyopathie.  Klin Padiatr. 1993;  205 185-189
    PubMedGoogle Scholar
  • 28 Du Pre C T, Fincher R M. Holt-Oram syndrome associated with hypoplastic peripheral vasculature and midsystolic click.  South Med J. 1993;  86 453-456
    PubMedGoogle Scholar
  • 29 Seling A. Schrittmacher bei Holt-Oram Syndrom.  Zentralbl Chir. 1968;  93 1488-1492
    PubMedGoogle Scholar
  • 30 Lewis K B, Bruce R A, Baum D, Motulsky A G. The upper limb-cardiovascular syndrome. An autosomal dominant genetic effect on embryogenesis.  JAMA. 1965;  193 1080-1086
    CrossrefPubMedGoogle Scholar
  • 31 Rainer W G, Sadler T R, Dirks D W, Swan H. Holt-Oram syndrome. Surgical implications.  J Thorac Cardiovasc Surg. 1972;  63 478-481
    PubMedGoogle Scholar
  • 32 Sealy W C, Farmer J C, Young W G, Brown I W. Atrial dysrhythmia and atrial secundum defects.  J Thorac Cardiovasc. 1969;  47 245
    PubMedGoogle Scholar
  • 33 Brons J T, van Geijn H P, Wladimiroff J W, van der Harten J J, Kwee M L, Sobotka-Plojhar M, Arts N F. Prenatal ultrasound diagnosis of the Holt-Oram syndrome.  Prenat Diagn. 1988;  8 175-181
    PubMedGoogle Scholar

Torsten Bossert

Department of Cardiac Surgery, University of Leipzig Heart Center

Strümpellstr. 39


04289 Leipzig

Germany

Phone: +49 (341) 8651421

Fax: +49 (341) 8651452

Email: Tbossert11@aol.com