Related Experiment Videos
Insights
Holt-Oram syndrome links upper limb skeletal defects with congenital heart disease. This study highlights left-sided asymmetry and the potential for transmission from affected individuals, even with isolated skeletal issues.
Area of Science:
- Genetics
- Cardiology
- Orthopedics
Background:
- Holt-Oram syndrome is an autosomal dominant disorder.
- It involves upper extremity skeletal malformations and congenital heart disease.
- The severity of skeletal and cardiac defects often varies.
Purpose of the Study:
- To review clinical experiences with Holt-Oram syndrome.
- To identify and emphasize previously under-recognized features of the syndrome.
- To improve understanding of its genetic transmission and clinical presentation.
Main Methods:
- Retrospective review of 39 patients with Holt-Oram syndrome.
- Analysis of skeletal and cardiac defect types and severity.
- Assessment of family history and mutation status.
Main Results:
- Observed wide variability in skeletal and cardiac defects.
- Noted striking left-sided asymmetry in skeletal involvement.
- Identified transmission of both skeletal and cardiac defects from parents with only skeletal issues.
- Found hypoplastic peripheral vessels complicating cardiac catheterization.
- Observed inconsistent electrocardiographic findings in secundum atrial septal defects.
Conclusions:
- Holt-Oram syndrome exhibits significant phenotypic variability.
- Asymmetry, particularly left-sided, is a notable feature.
- Genetic transmission can occur even with isolated skeletal abnormalities.
- Associated vascular anomalies and diagnostic challenges exist.
- ECG findings may not be uniformly present in all cases.
Abstract:
The autosomal dominant association of upper extremity skeletal defects with congenital heart disease is known as the Holt-Oram syndrome. We reviewed our experience with 39 affected patients of whom 15 were considered new mutations. Wide varieties of skeletal defects and congenital heart disease were observed, and the severity of skeletal involvement did not parallel that of cardiac disease. These patients demonstrate four previously unemphasized points: (1) There is a striking asymmetry of skeletal involvement, with the left side more severely affected. (2) Patients with skeletal defects alone can transmit both skeletal and cardiac defects to their children. (3) Hypoplastic peripheral vessels may be an associated abnormality and can result in difficulty with cardiac catheterization. (4) Electrocardiographic changes of terminal conduction delay in the right anterior chest leads were nor uniformly present in patients with otherwise typical secundum atrial septal defects.