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Variation in severity of cardiac disease in Holt-Oram syndrome
1Ray and Hattie Anderson Center for the study of Hereditary Cardiac Disease, Department of Pediatrics, University-Variety Hospital for Children, University of Minnesota, Minneapolis, USA.
Insights
Holt-Oram syndrome (HOS) presents with varied heart defects, including complex congenital heart malformations not typically expected. This highlights the need for better understanding of HOS cardiac spectrum severity.
Area of Science:
- Genetics
- Cardiology
- Developmental Biology
Background:
- Holt-Oram syndrome (HOS) is a genetic disorder characterized by congenital heart defects and upper limb abnormalities.
- Existing literature often associates HOS with less severe or isolated cardiac defects like atrial septal defects.
Observation:
- This study details a family with HOS exhibiting variable hand and cardiac manifestations, including complex congenital heart malformations.
- One family member presented with an endocardial cushion defect and hypoplasia of the left ventricle.
Findings:
- A review of literature (1974-1995) indicates atrial septal defects are the most common cardiac anomaly in HOS (60.3%).
- However, a significant proportion (17.5%) of cases present with more complex congenital heart malformations requiring extensive medical and surgical intervention.
- This challenges the common perception of HOS cardiac involvement.
Implications:
- Findings underscore the importance of recognizing the broader spectrum of cardiac severity in Holt-Oram syndrome.
- Enhanced genetic counseling and clinical surveillance are crucial for families affected by HOS.
- Further research is needed to elucidate the genetic and molecular mechanisms underlying the diverse cardiac phenotypes in HOS.
Abstract:
We describe a family with Holt-Oram syndrome (HOS) with variable hand and cardiac manifestations. One affected relative had complex congenital malformations of the heart consisting of an endocardial cushion defect and hypoplasia of the left ventricle. The literature from 1974 to 1995 is reviewed. Atrial septal defect is the most cardiac abnormality (60.3% of 189 cases) occurring singly or in combination with other malformations. Thirty-three individuals (17.5%) of literature cases) have more complex congenital malformations of the heart requiring complicated medical management and extensive cardiac surgery. Many genetic reference sources of HOS indicate that single or less severe cardiac malformations are expected in this disorder. It is important to provide more information about the occurrence and spectrum of severity of malformations of the heart to individuals and families where HOS is present.