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J Med Genet. 1996 April; 33(4): 300–307.
PMCID: PMC1050579

Holt-Oram syndrome: a clinical genetic study.

Abstract

A clinical and genetic study of the Holt-Oram syndrome (HOS) has been carried out in the United Kingdom involving 55 cases designated Holt-Oram syndrome, together with their parents and sibs. Data from the clinical assessment of both familial and isolated cases were used to define the HOS phenotype and to outline the spectrum of abnormalities, especially factors affecting severity. Skeletal defects affected the upper limbs exclusively and were bilateral and asymmetrical. They ranged from minor signs such as clinodactyly, limited supination, and sloping shoulders to severe reduction deformities of the upper arm (4.5%). The radial ray was predominantly affected than the right. All affected cases showed evidence of upper limb involvement. Cardiac defects were seen in 95% of familial cases and included both atrial septal defect (ASD, 34%) and ventricular septal defect (VSD, 25%); 39% had only ECG changes. Cardiac involvement ranged from asymptomatic conduction disturbances to multiple structural defects requiring surgery in infancy. Sudden death could be caused by heart block. Inheritance was autosomal dominant with 100% penetrance and no evidence of reduced fitness. Increasing severity occurred in succeeding generations consistent with anticipation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • HOLT M, ORAM S. Familial heart disease with skeletal malformations. Br Heart J. 1960 Apr;22:236–242. [PMC free article] [PubMed]
  • Smith AT, Sack GH, Jr, Taylor GJ. Holt-Oram syndrome. J Pediatr. 1979 Oct;95(4):538–543. [PubMed]
  • HOLMES LB. CONGENITAL HEART DISEASE AND UPPER-EXTREMITY DEFORMITIES: A REPORT OF TWO FAMILIES. N Engl J Med. 1965 Mar 4;272:437–444. [PubMed]
  • Gardner RJ, Buckfield PM, Veale AM. A girl with severe expression of the holt-oram gene. Clin Genet. 1973;4(5):417–421. [PubMed]
  • Cascos AS. Holt-Oram syndrome. Acta Paediatr Scand. 1967 May;56(3):313–317. [PubMed]
  • Lewis KB, Bruce RA, Baum D, Motulsky AG. The upper limb-cardiovascular syndrome. An autosomal dominant genetic effect on embryogenesis. JAMA. 1965 Sep 27;193(13):1080–1086. [PubMed]
  • Terrett JA, Newbury-Ecob R, Cross GS, Fenton I, Raeburn JA, Young ID, Brook JD. Holt-Oram syndrome is a genetically heterogeneous disease with one locus mapping to human chromosome 12q. Nat Genet. 1994 Apr;6(4):401–404. [PubMed]
  • Gall JC, Jr, Stern AM, Cohen MM, Adams MS, Davidson RT. Holt-Oram syndrome: clinical and genetic study of a large family. Am J Hum Genet. 1966 Mar;18(2):187–200. [PubMed]
  • Gladstone I, Jr, Sybert VP. Holt-Oram syndrome: penetrance of the gene and lack of maternal effect. Clin Genet. 1982 Feb;21(2):98–103. [PubMed]
  • Carroll RE, Louis DS. Anomalies associated with radial dysplasia. J Pediatr. 1974 Mar;84(3):409–411. [PubMed]
  • Bosi G, Sensi A, Calzolari E, Scorrano M. Familial atrial septal defect with prolonged atrioventricular conduction. Am J Med Genet. 1992 Jun 1;43(3):641–641. [PubMed]
  • Brans YW, Lintermans JP. The upper limb-cardiovascular syndrome. A report of two African cases with a review of the literature. Am J Dis Child. 1972 Nov;124(5):779–783. [PubMed]
  • Silengo MC, Biagioli M, Guala A, Lopez-Bell G, Lala R. Heart-hand syndrome II. A report of Tabatznik syndrome with new findings. Clin Genet. 1990 Aug;38(2):105–113. [PubMed]
  • Ruiz de la Fuente S, Prieto F. Heart-hand syndrome. III. A new syndrome in three generations. Hum Genet. 1980;55(1):43–47. [PubMed]
  • Hollister DW, Hollister WG. The "long-thumb" brachydactyly syndrome. Am J Med Genet. 1981;8(1):5–16. [PubMed]
  • Hall JG. Thrombocytopenia and absent radius (TAR) syndrome. J Med Genet. 1987 Feb;24(2):79–83. [PMC free article] [PubMed]
  • Glanz A, Fraser FC. Spectrum of anomalies in Fanconi anaemia. J Med Genet. 1982 Dec;19(6):412–416. [PMC free article] [PubMed]
  • Khoury MJ, Cordero JF, Greenberg F, James LM, Erickson JD. A population study of the VACTERL association: evidence for its etiologic heterogeneity. Pediatrics. 1983 May;71(5):815–820. [PubMed]
  • Basson CT, Cowley GS, Solomon SD, Weissman B, Poznanski AK, Traill TA, Seidman JG, Seidman CE. The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome) N Engl J Med. 1994 Mar 31;330(13):885–891. [PubMed]
  • Kaufman RL, Rimoin DL, McAlister WH, Hartmann AF. Variable expression of the Holt-Oram syndrome. Am J Dis Child. 1974 Jan;127(1):21–25. [PubMed]
  • Brons JT, van Geijn HP, Wladimiroff JW, van der Harten JJ, Kwee ML, Sobotka-Plojhar M, Arts NF. Prenatal ultrasound diagnosis of the Holt-Oram syndrome. Prenat Diagn. 1988 Mar;8(3):175–181. [PubMed]
  • Van Regemorter N, Haumont D, Kirkpatrick C, Viseur P, Jeanty P, Dodion J, Milaire J, Rooze M, Rodesch F. Holt Oram syndrome mistaken for thalidomide embryopathy--embryological considerations. Eur J Pediatr. 1982 Feb;138(1):77–80. [PubMed]
  • Brook JD. Retreat of the triplet repeat? Nat Genet. 1993 Apr;3(4):279–281. [PubMed]

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