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Pediatric Holt-Oram Syndrome Treatment & Management

  • Author: Poothirikovil Venugopalan, MBBS, MD, FRCPCH; Chief Editor: P Syamasundar Rao, MD  more...
 
Updated: Aug 05, 2015
 

Medical Care

Acute-stage management in patients with Holt-Oram syndrome

Treatment is directed at the cardiac manifestations. Care may be necessary with exacerbations of heart failure, for interventional procedures, or for surgical correction of heart disease. Administer medications as dictated by the heart disease.

Establish a complete diagnosis, and counsel the patient and family.

Consultations

Consult with the following:

  • Pediatric cardiologist
  • Orthopedic specialist
  • Radiologist
  • Nuclear medicine specialist
  • Family physician
  • Occupational therapist
  • Physiotherapist
  • Psychologist
  • School teacher
  • Specialist nurse
  • Pharmacist
  • Dietitian

Transfer

Transfer may be necessary for further evaluation and surgical intervention.

Diet and activity

Patients with Holt-Oram syndrome may require dietary modification because of their specific cardiac abnormality.

No activity restrictions are required unless a specific cardiac abnormality indicates otherwise.

Outpatient monitoring

Regular follow-up is essential for both cardiac and skeletal conditions. The patient should be seen by orthopedic and occupational therapists, as well as by physiotherapists.

At each visit, the importance of prevention of deformity must be emphasized.

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Surgical Care

Cardiact defect

Treatment for the heart defect includes the following:

  • Appropriate surgical or nonsurgical correction of the heart defect is indicated and possible. A vast majority of atrial septal defects may be closed by transcatheter methods.
  • Palliative surgery, as indicated, if complete correction is not possible

Musculoskeletal defects

Treatment for musculoskeletal defects may include the following:

  • Take adequate measures to prevent acquired deformities and to treat existing deformities.
  • Surgical management of hand anomalies depends on the age, pattern, and degree of accompanying malformations of the upper limb.
  • Pollicization to improve function of index finger is recommended for patients with aplasia of the thumb. This is also recommended following amputation of a rudimental thumb.
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Long-Term Monitoring

 

 

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Contributor Information and Disclosures
Author

Poothirikovil Venugopalan, MBBS, MD, FRCPCH Consultant Pediatrician with Cardiology Expertise, Department of Child Health, Brighton and Sussex University Hospitals, NHS Trust; Honorary Senior Clinical Lecturer, Brighton and Sussex Medical School, UK

Poothirikovil Venugopalan, MBBS, MD, FRCPCH is a member of the following medical societies: Royal College of Paediatrics and Child Health, Paediatrician with Cardiology Expertise Special Interest Group, British Congenital Cardiac Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

John W Moore, MD, MPH Professor of Clinical Pediatrics, Section of Pediatic Cardiology, Department of Pediatrics, University of California San Diego School of Medicine; Director of Cardiology, Rady Children's Hospital

John W Moore, MD, MPH is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, Society for Cardiovascular Angiography and Interventions

Disclosure: Nothing to disclose.

Chief Editor

P Syamasundar Rao, MD Professor of Pediatrics and Medicine, Division of Cardiology, Emeritus Chief of Pediatric Cardiology, University of Texas Medical School at Houston and Children's Memorial Hermann Hospital

P Syamasundar Rao, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, American College of Cardiology, American Heart Association, Society for Cardiovascular Angiography and Interventions, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Ira H Gessner, MD Professor Emeritus, Pediatric Cardiology, University of Florida College of Medicine

Ira H Gessner, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, American Pediatric Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

References
  1. Garavelli L, De Brasi D, Verri R, Guareschi E, Cariola F, Melis D, et al. Holt-Oram syndrome associated with anomalies of the feet. Am J Med Genet A. 2008 May 1. 146A(9):1185-9. [Medline].

  2. Al-Qattan MM, Abou Al-Shaar H. Molecular basis of the clinical features of Holt-Oram syndrome resulting from missense and extended protein mutations of the TBX5 gene as well as TBX5 intragenic duplications. Gene. 2015 Apr 15. 560 (2):129-36. [Medline].

  3. Postma AV, van de Meerakker JB, Mathijssen IB, et al. A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation. Circ Res. 2008 Jun 6. 102(11):1433-42. [Medline].

  4. Bohm J, Heinritz W, Craig A, et al. Functional analysis of the novel TBX5 c.1333delC mutation resulting in an extended TBX5 protein. BMC Med Genet. 2008 Oct 1. 9:88. [Medline]. [Full Text].

  5. Ogur G, Gul D, Lenk MK, Imirzalioglu N, Alpay F, Ogur E. Variable clinical expression of Holt-Oram syndrome in three generations. Turk J Pediatr. 1998 Oct-Dec. 40(4):613-8. [Medline].

  6. Cachat F, Rapatsalahy A, Sekarski N, Hurni M, von Segesser L, Payot M. [Three different types of atrial septal defects in the same family]. Arch Mal Coeur Vaiss. 1999 May. 92(5):667-9. [Medline].

  7. D Franklin A, Lorinc AN, Donahue BS. Malignant Hyperthermia-Like Manifestations in a Two-Month-Old Child with Holt-Oram Syndrome Undergoing Cardiac Surgery. J Cardiothorac Vasc Anesth. 2013 Sep 5. [Medline].

  8. Barisic I, Boban L, Greenlees R, et al. Holt Oram syndrome: a registry-based study in Europe. Orphanet J Rare Dis. 2014 Oct 25. 9:156. [Medline].

  9. Goldfarb CA, Wall L, Manske PR, et al. Radial longitudinal deficiency: the incidence of associated medical and musculoskeletal conditions. J Hand Surg [Am]. 2006 Sep. 31(7):1176-82. [Medline].

  10. McDermott DA, Hatcher CJ, Basson CT. Atrial Fibrillation and Other Clinical Manifestations of Altered TBX5 Dosage in Typical Holt-Oram Syndrome. Circ Res. 2008 Sep 26. 103(7):e96. [Medline]. [Full Text].

  11. Postma AV, van de Meerakker JB, Mathijssen IB, Barnett P, Christoffels VM, Ilgun A, et al. A gain-of-function TBX5 mutation is associated with atypical Holt-Oram syndrome and paroxysmal atrial fibrillation. Circ Res. 2008 Jun 6. 102(11):1433-42. [Medline].

  12. Chryssostomidis G, Kanakis M, Fotiadou V, et al. Diversity of congenital cardiac defects and skeletal deformities associated with the Holt-Oram syndrome. Int J Surg Case Rep. 2014. 5 (7):389-92. [Medline].

  13. Jhang WK, Lee BH, Kim GH, Lee JO, Yoo HW. Clinical and molecular characterisation of Holt-Oram syndrome focusing on cardiac manifestations. Cardiol Young. 2015 Aug. 25 (6):1093-8. [Medline].

  14. Garavelli L, De Brasi D, Verri R, Guareschi E, Cariola F, Melis D, et al. Holt-Oram syndrome associated with anomalies of the feet. Am J Med Genet A. 2008 May 1. 146A(9):1185-9. [Medline].

  15. Mglinets VA. [Hand dermatoglyphics in patients with isolated triphalangia and Holt-Oram syndrome]. Genetika. 1995 Aug. 31(8):1147-53. [Medline].

  16. Tseng YR, Su YN, Lu FL, et al. Holt-Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene. Am J Med Genet A. 2007 May 1. 143A(9):1012-4. [Medline].

  17. Smets K, Mortier G, Zecic A. Perinatal/neonatal case presentation: unexpected severe respiratory insufficiency in a newborn with Holt-Oram Syndrome. J Perinatol. 2005 Nov. 25(11):745-6. [Medline].

  18. Allanson JE, Newbury-Ecob RA. Holt-Oram syndrome: is there a "face"?. Am J Med Genet A. 2003 May 1. 118(4):314-8. [Medline].

  19. Basson CT, Cowley GS, Solomon SD, et al. The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome). N Engl J Med. 1994 Mar 31. 330(13):885-91. [Medline]. [Full Text].

  20. Basson CT, Huang T, Lin RC, Bachinsky DR, Weremowicz S, Vaglio A, et al. Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. Proc Natl Acad Sci U S A. 1999 Mar 16. 96(6):2919-24. [Medline]. [Full Text].

  21. Basson CT, Solomon SD, Weissman B, et al. Genetic heterogeneity of heart-hand syndromes. Circulation. 1995 Mar 1. 91(5):1326-9. [Medline]. [Full Text].

  22. Benson DW, Basson CT, MacRae CA. New understandings in the genetics of congenital heart disease. Curr Opin Pediatr. 1996 Oct. 8(5):505-11. [Medline].

  23. Bohm M. Holt-Oram syndrome. Circulation. 1998 Dec 8. 98(23):2636-7. [Medline]. [Full Text].

  24. Borozdin W, Bravo Ferrer Acosta AM, Bamshad MJ, et al. Expanding the spectrum of TBX5 mutations in Holt-Oram syndrome: detection of two intragenic deletions by quantitative real time PCR, and report of eight novel point mutations. Hum Mutat. 2006 Sep. 27(9):975-6. [Medline].

  25. Borozdin W, Bravo-Ferrer Acosta AM, Seemanova E, et al. Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes. Am J Med Genet A. 2006 Sep 1. 140(17):1880-6. [Medline].

  26. Bossert T, Walther T, Gummert J, et al. Cardiac malformations associated with the Holt-Oram syndrome--report on a family and review of the literature. Thorac Cardiovasc Surg. 2002 Oct. 50(5):312-4. [Medline].

  27. Brassington AM, Sung SS, Toydemir RM, Le T, Roeder AD, Rutherford AE, et al. Expressivity of Holt-Oram syndrome is not predicted by TBX5 genotype. Am J Hum Genet. 2003 Jul. 73(1):74-85. [Medline]. [Full Text].

  28. Brockhoff CJ, Kober H, Tsilimingas N, et al. Holt-Oram syndrome. Circulation. 1999 Mar 16. 99(10):1395-6. [Medline]. [Full Text].

  29. Bruneau BG, Logan M, Davis N, et al. Chamber-specific cardiac expression of Tbx5 and heart defects in Holt-Oram syndrome. Dev Biol. 1999 Jul 1. 211(1):100-8. [Medline].

  30. Cheng TO. Persistent left superior vena cava in Holt-Oram syndrome. Int J Cardiol. 2000 Oct. 76(1):83, 81-2. [Medline].

  31. DuPre CT, Fincher RM. Holt-Oram syndrome associated with hypoplastic peripheral vasculature and midsystolic click. South Med J. 1993 Apr. 86(4):453-6. [Medline].

  32. Ekure EN, Okoromah CN, Briggs E, Ajenifuja OA. Holt-Oram syndrome with hypoplastic left heart syndrome in an African child. Niger Postgrad Med J. 2004 Sep. 11(3):190-2. [Medline].

  33. Fan C, Liu M, Wang Q. Functional analysis of TBX5 missense mutations associated with Holt-Oram syndrome. J Biol Chem. 2003 Mar 7. 278(10):8780-5. [Medline]. [Full Text].

  34. Gruenauer-Kloevekorn C, Reichel MB, Duncker GI, Froster UG. Molecular genetic and ocular findings in patients with holt-oram syndrome. Ophthalmic Genet. 2005 Mar. 26(1):1-8. [Medline].

  35. Hatcher CJ, Kim MS, Mah CS, et al. TBX5 transcription factor regulates cell proliferation during cardiogenesis. Dev Biol. 2001 Feb 15. 230(2):177-88. [Medline].

  36. He J, McDermott DA, Song Y, et al. Preimplantation genetic diagnosis of human congenital heart malformation and Holt-Oram syndrome. Am J Med Genet A. 2004 Apr 1. 126(1):93-8.

  37. Heinritz W, Moschik A, Kujat A, et al. Identification of new mutations in the TBX5 gene in patients with Holt-Oram syndrome. Heart. 2005 Mar. 91(3):383-4. [Medline]. [Full Text].

  38. Heinritz W, Shou L, Moschik A, Froster UG. The human TBX5 gene mutation database. Hum Mutat. 2005 Oct. 26(4):397. [Medline].

  39. Holt M, Oram S. Familial heart disease with skeletal malformations. Br Heart J. 1960 Apr. 22:236-42. [Medline].

  40. Horb ME, Thomsen GH. Tbx5 is essential for heart development. Development. 1999 Apr. 126(8):1739-51. [Medline]. [Full Text].

  41. Hurst JA, Hall CM, Baraitser M. The Holt-Oram syndrome. J Med Genet. 1991 Jun. 28(6):406-10. [Medline].

  42. Keller BB. Developmental structure-function insights from Tbx5(del/+) mouse model of Holt-Oram syndrome. Am J Physiol Heart Circ Physiol. 2005 Sep. 289(3):H975-6. [Medline]. [Full Text].

  43. Kohlhase J, Chitayat D, Kotzot D, et al. SALL4 mutations in Okihiro syndrome (Duane-radial ray syndrome), acro-renal-ocular syndrome, and related disorders. Hum Mutat. 2005 Sep. 26(3):176-83. [Medline].

  44. Koishizawa T, Hayashi N, Tadokoro M, et al. [A case report of the radical correction of a truncus arteriosus and peripheral pulmonary stenosis in association with Holt-Oram syndrome]. Kyobu Geka. 1995 Feb. 48(2):133-6. [Medline].

  45. Koutlas ED, Papageorgiou AA, Athyros VG. Holt-Oram syndrome with malformations of renal and cerebral arteries. Acta Cardiol. 1996. 51(4):373-6. [Medline].

  46. Le Meur N, Goldenberg A, Michel-Adde C, et al. Molecular characterization of a 14q deletion in a boy with features of Holt-Oram syndrome. Am J Med Genet A. 2005 May 1. 134(4):439-42. [Medline].

  47. Lee ML, Tsao LY, Wang YM. Interventional cardiac catheterization for the coarctation of the aortic arch and patent ductus arteriosus in a 3-day-old neonate with the Holt-Oram syndrome. Int J Cardiol. 2005 Jun 8. 101(3):503-5. [Medline].

  48. Lehner R, Goharkhay N, Tringler B, et al. Pedigree analysis and descriptive investigation of three classic phenotypes associated with Holt-Oram syndrome. J Reprod Med. 2003 Mar. 48(3):153-9. [Medline].

  49. McDermott DA, Bressan MC, He J, et al. TBX5 genetic testing validates strict clinical criteria for Holt-Oram syndrome. Pediatr Res. 2005 Nov. 58(5):981-6. [Full Text].

  50. McDermott DA, He J, Song YS, et al. Update: PGD and Holt-Oram syndrome. Am J Med Genet A. 2005 Jul 15. 136(2):223. [Medline].

  51. Moskowitz IP, Pizard A, Patel VV, et al. The T-Box transcription factor Tbx5 is required for the patterning and maturation of the murine cardiac conduction system. Development. 2004 Aug. 131(16):4107-16. [Medline]. [Full Text].

  52. Murakami M, Nakagawa M, Olson EN, Nakagawa O. A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome. Proc Natl Acad Sci U S A. 2005 Dec 13. 102(50):18034-9. [Medline]. [Full Text].

  53. Newbury-Ecob RA, Leanage R, Raeburn JA, Young ID. Holt-Oram syndrome: a clinical genetic study. J Med Genet. 1996 Apr. 33(4):300-7. [Medline].

  54. Pizard A, Burgon PG, Paul DL, Bruneau BG, Seidman CE, Seidman JG. Connexin 40, a target of transcription factor Tbx5, patterns wrist, digits, and sternum. Mol Cell Biol. 2005 Jun. 25(12):5073-83. [Medline]. [Full Text].

  55. Plageman TF, Yutzey KE. Microarray analysis of Tbx5-induced genes expressed in the developing heart. Dev Dyn. 2006 Oct. 235(10):2868-80. [Medline].

  56. Porsch M, Hofmeyer K, Bausenwein BS, et al. Isolation of a Drosophila T-box gene closely related to human TBX1. Gene. 1998 Jun 8. 212(2):237-48. [Medline].

  57. Schneider MD, Schwartz RJ. Heart or hand? Unmasking the basis for specific Holt-Oram phenotypes. Proc Natl Acad Sci U S A. 1999 Mar 16. 96(6):2577-8. [Medline]. [Full Text].

  58. Shono S, Higa K, Kumano K, Dan K. Holt-Oram syndrome. Br J Anaesth. 1998 Jun. 80(6):856-7. [Medline]. [Full Text].

  59. Sinkovec M, Petrovic D, Volk M, Peterlin B. Familial progressive sinoatrial and atrioventricular conduction disease of adult onset with sudden death, dilated cardiomyopathy, and brachydactyly. A new type of heart-hand syndrome?. Clin Genet. 2005 Aug. 68(2):155-60. [Medline].

  60. Smets K, Mortier G, Zecic A. Perinatal/neonatal case presentation: unexpected severe respiratory insufficiency in a newborn with Holt-Oram Syndrome. J Perinatol. 2005 Nov. 25(11):745-6. [Medline].

  61. Terrett JA, Newbury-Ecob R, Smith NM, Li QY, Garrett C, Cox P, et al. A translocation at 12q2 refines the interval containing the Holt-Oram syndrome 1 gene. Am J Hum Genet. 1996 Dec. 59(6):1337-41. [Medline]. [Full Text].

  62. Tucker KJ, Murphy J, Conti JB, Curtis AB. Syncope and sinus arrest associated with the upper limb-cardiovascular (Holt-Oram) syndrome. Pacing Clin Electrophysiol. 1994 Oct. 17(10):1678-80. [Medline].

  63. Weber M, Wenz W, van Riel A, et al. [The Holt-Oram syndrome. Review of the literature and current orthopedic treatment concepts]. Z Orthop Ihre Grenzgeb. 1997 Jul-Aug. 135(4):368-75. [Medline].

  64. Wilson GN. Correlated heart/limb anomalies in Mendelian syndromes provide evidence for a cardiomelic developmental field. Am J Med Genet. 1998 Apr 1. 76(4):297-305. [Medline].

  65. Yi CH, Terrett JA, Li QY, et al. Identification, mapping, and phylogenomic analysis of four new human members of the T-box gene family: EOMES, TBX6, TBX18, and TBX19. Genomics. 1999 Jan 1. 55(1):10-20. [Medline].

  66. Zaragoza MV, Lewis LE, Sun G, et al. Identification of the TBX5 transactivating domain and the nuclear localization signal. Gene. 2004 Apr 14. 330:9-18. [Medline].

  67. Zhou YQ, Zhu Y, Bishop J, et al. Abnormal cardiac inflow patterns during postnatal development in a mouse model of Holt-Oram syndrome. Am J Physiol Heart Circ Physiol. 2005 Sep. 289(3):H992-H1001. [Medline]. [Full Text].

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Photograph showing hypoplastic right thumb of the right hand of a 6-month-old infant with Holt-Oram syndrome.
Photograph of the left hand of a 6-month-old infant with Holt-Oram syndrome showing total aplasia of the left thumb.
Plain radiograph of the right forearm and hand of a 5-month-old infant with Holt-Oram syndrome showing hypoplastic radius and ulna and only 4 metacarpals.
A 2-dimensional echocardiographic picture taken from subxiphoid window showing a large secundum atrial septal defect (arrow) in a 7-year-old boy with Holt-Oram syndrome. ASD = Atrial septal defect; RA = Right atrium; RV = Right ventricle; LA = Left atrium; LV = Left ventricle.
Color Doppler echocardiographic picture taken from subxiphoid window showing the large left-to-right flow of blood (arrow) across the atrial septal defect. The red color pattern depicts flow direction from left atrium (LA) to right atrium (RA). ASD = Atrial septal defect; RA = Right atrium; RV = Right ventricle; LA = Left atrium; LV = Left ventricle.
 
 
 
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