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Variability of the Holt-Oram syndrome in Saudi individuals
H Najjar1, M Mardini, R Tabbaa
1Department of Pediatrics, King Faisal Hospital and Research Centre, Riyadh, Saudi Arabia.
Insights
Holt-Oram syndrome (HOS) involves skeletal abnormalities and heart defects. This study details HOS presentations across three families, noting varied inheritance patterns including new mutations and autosomal dominant transmission.
Area of Science:
- Genetics
- Cardiology
- Orthopedics
Background:
- Holt-Oram syndrome (HOS) is a genetic disorder characterized by upper limb malformations and congenital heart disease.
- Understanding the genetic basis and phenotypic variability of HOS is crucial for diagnosis and management.
Observation:
- Three families with HOS patients were studied, exhibiting diverse skeletal and cardiac anomalies.
- Specific observations included absent thumbs, hypoplastic radii, atrial and ventricular septal defects, pulmonary stenosis, and tetralogy of Fallot.
- Phenotypic expression varied, with some individuals showing only thumb abnormalities and others severe cardiac and limb defects.
Findings:
- HOS manifestations ranged from triphalangeal thumbs with atrial septal defects to tetralogy of Fallot with hypoplastic pulmonary artery.
- Genetic analysis suggested new mutations in two families and autosomal dominant inheritance in one family.
- The study highlights the broad spectrum of Holt-Oram syndrome, impacting both skeletal and cardiovascular systems.
Implications:
- These findings underscore the importance of comprehensive cardiac and skeletal evaluations in patients diagnosed with HOS.
- Recognizing the varied inheritance patterns aids in genetic counseling and risk assessment for affected families.
- Further research into the molecular mechanisms underlying HOS can lead to improved diagnostic tools and targeted therapies.
Abstract:
We studied three families in which patients with the Holt-Oram syndrome (HOS) had various skeletal abnormalities and congenital heart defects. Two patients had absent thumbs and first metacarpals, hypoplastic radii, and atrial and ventricular septal defects. Patient 2 had pulmonary stenosis, an atrial septal defect, and triphalangeal thumbs. A sister had atrial septal defect and abnormalities of the thumbs; two brothers had abnormalities of the thumbs. The mother had unilateral defect of the thumb with a normal heart. The third patient had tetralogy of Fallot and hypoplastic pulmonary artery. In two families the HOS appeared to be the result of new mutations; in one it was transmitted as an autosomal dominant trait.