eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Cardiology

Holt-Oram Syndrome: Differential Diagnoses & Workup

Author: Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH, Consulting Staff, Department of Child Health, University Hospital of Hartlepool, UK
Contributor Information and Disclosures

Updated: Nov 7, 2008

Differential Diagnoses

Atrial Septal Defect, General Concepts
Thrombocytopenia-Absent Radius Syndrome

Other Problems to Be Considered

The following syndromes do not include atrial septal defect (ASD) and do not map to band 12q2:

  • Heart-hand syndrome type II (Tobatznik syndrome)
  • Heart-hand syndrome type III (OMIM 140450)
Other problems to be considered include the following:
  • Okihiro/Duane-radial ray syndrome (DRRS)
  • Coloboma, heart disease, atresia, choanae, retarded growth and retarded development and/or CNS anomalies, genital hypoplasia, and ear anomalies and/or deafness (CHARGE) association
  • Fanconi anemia
  • Thalidomide embryopathy
  • Vertebral defects, imperforate anus, tracheoesophageal fistula, radial and renal dysplasia (VATER) and/or vertebral, anal, cardiac, tracheal, esophageal, renal, limb (VACTERL) association

Workup

Laboratory Studies

  • Blood tests are required for molecular genetics in patients with Holt-Oram syndrome (HOS) and for management because the cardiac anomaly present may be a major one that causes and cause symptoms or requires intervention.

Imaging Studies

  • Imaging studies of upper limbs
    • The scapula may be raised and small, with abnormalities at the acromial region, a prominent coracoclavicular joint, and a small glenoid fossa.
    • The humerus may be hypoplastic or absent in patients with phocomelia. In other patients, the medial epicondyles are large and the humeral head may be deformed with epiphyseal irregularities. Radioulnar and humeroulnar synostosis, radial hypoplasia or absence, and ulnar absence are all reported.
    • Scaphoid anomalies are particularly common and include hypoplasia and bipartite ossification. In the normal fetus, a scaphoid bone called the os central (representing a third row of carpal centres) usually fuses with the scaphoid, but this may not occur in patients with HOS.
    • Additional carpal bones may be present. Other carpal anomalies include absence, hypoplasia, enlargement, irregularity, and fusion.
    • The first through fifth metacarpals may have both proximal and distal epiphyses. Structural changes such as hypoplasia may be present.
  • Chest radiography: Chest radiography findings are either normal or reflect the type of cardiac abnormality.
  • Doppler-echocardiography (ECHO) evaluation
    • This study is used to reveal the primary heart defect, its severity, and associated cardiac malformations.
    • It also allows estimation of certain hemodynamic values, such as blood flow and chamber pressure. However, reliability of some of these measurements is limited.
    • Doppler ECHO is indicated in the newborn with a skeletal abnormality suggestive of HOS.
  • MRI
    • This is helpful for delineating cardiac and skeletal involvement.
    • MRI may also be used to confirm muscular hypoplasia and to help distinguish the muscle involvement from those of any coexisting progressive neuromuscular disorders.

Other Tests

  • Electrocardiography
    • This test reveals the features of the underlying heart defect. The most common defect, secundum ASD, usually demonstrates right atrial enlargement and right ventricular enlargement.
    • Cardiac rhythm disturbances include both tachyarrhythmia and bradyarrhythmia. Prominent among these are heart blocks (first-degree, second-degree, or third-degree), wandering atrial pacemaker, and sinus bradycardia.
  • Twenty-four–hour Holter ECG
    • This test reveals paroxysmal tachycardia, especially atrial tachycardia. Occasional sinus pauses or sinus arrest is found.
    • This test is especially important in patients with a history of syncope.
  • Karyotyping and molecular studies
    • Detailed cytogenetic analysis may help to map the breakpoints within the critical area of 12q.
    • This study requires a combination of chromosome painting and fluorescent in situ hybridization (FISH) with yeast artificial chromosomes (YAC) and cosmids.
  • Prenatal diagnosis
    • Amniocentesis and chorionic villus biopsy may be indicated based on the family history.
    • Fetal ultrasonography may reveal a skeletal abnormality suggestive of HOS.
    • Prenatal diagnosis is feasible in families with HOS linked to band 12q2.
    • DNA-based diagnosis must be coupled with noninvasive fetal imaging techniques to define phenotypic manifestations.

Procedures

  • Cardiac catheterization and angiography

    • These are performed in selected patients in whom echocardiographic findings are either inconclusive or more accurate hemodynamic assessment is considered necessary.
    • Findings reflect the specific cardiac abnormality.
    • Complications during the procedure may include blood vessel rupture, tachyarrhythmias, bradyarrhythmias, and vascular occlusion.
    • Postcatheterization problems include hemorrhage, vascular disruption after balloon dilation, pain, nausea and vomiting, and arterial or venous obstruction due to thrombosis or spasm.

More on Holt-Oram Syndrome

Overview: Holt-Oram Syndrome
Differential Diagnoses & Workup: Holt-Oram Syndrome
Treatment & Medication: Holt-Oram Syndrome
Follow-up: Holt-Oram Syndrome
Multimedia: Holt-Oram Syndrome
References
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Further Reading

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Keywords

Holt-Oram syndrome, HOS, embryonic radial ray, triphalangeal thumbs, absent thumbs, foreshortened arms, phocomelia, TBX5, atriodigital hypoplasia, cardiac-limb syndrome, cardiomelic syndrome, heart-hand syndrome, upper limb–cardiovascular syndrome, ventricular septal defect, VSD, atrial septal defect, ASD

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Contributor Information and Disclosures

Author

Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH, Consulting Staff, Department of Child Health, University Hospital of Hartlepool, UK
Poothirikovil Venugopalan, MBBS, MD, FRCP (Glasg), FRCPCH is a member of the following medical societies: British Cardiac Society and Royal College of Physicians and Surgeons of Glasgow
Disclosure: Nothing to disclose.

Medical Editor

Ira H Gessner, MD, Professor Emeritus, Pediatric Cardiology
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, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John W Moore, MD, MPH, Professor of Clinical Pediatrics, Section of Pediatric 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, and Society for Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

CME Editor

Gilbert Z Herzberg, MD, Assistant Professor, Department of Pediatrics, Section of Pediatric Cardiology, New York Medical College; Consulting Staff, Department of Pediatrics, Sound Shore Medical Center
Gilbert Z Herzberg, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Chief Editor

Steven R Neish, MD, SM, Director of Pediatric Cardiology Fellowship Program, Associate Professor, Department of Pediatrics, Baylor College of Medicine
Steven R Neish, MD, SM is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, and American Heart Association
Disclosure: Nothing to disclose.

 
 
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