Pediatric Holt-Oram Syndrome Workup

  • Author: Poothirikovil Venugopalan, MBBS, MD, FRCP(Glasg), FRCPCH; Chief Editor: Steven R Neish, MD, SM   more...
 
Updated: Jun 23, 2010
 

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.

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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 as depicted below.Color Doppler echocardiographic picture taken fromColor 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.
  • 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.
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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.
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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.
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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 North Tees and Hartlepool, UK

Poothirikovil Venugopalan, MBBS, MD, FRCP(Glasg), FRCPCH, is a member of the following medical societies: British Cardiac Society, Paediatrician with Cardiology Expertise Special Interest Group, Royal College of Paediatrics and Child Health, and Royal College of Physicians and Surgeons of Glasgow

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

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 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.

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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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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