About Holt-Oram Syndrome
Holt-Oram syndrome is a highly penetrant autosomal dominant condition caused by pathogenic variants in TBX5, a T-box transcription factor essential for upper limb and cardiac development, resulting in the combination of preaxial upper limb anomalies and congenital heart defects. Upper limb malformations range from subtle abnormalities of the carpal or thumb bones detectable only radiographically to phocomelia, and are invariably present; cardiac defects, most commonly atrial septal defect and ventricular septal defect, occur in approximately 75% of individuals. Conduction system abnormalities, including atrioventricular block, occur even in the absence of structural heart defects and may present in adulthood.
Common Clinical Features
Clinical Trial Eligibility Tips
What to know before applying to Holt-Oram Syndrome trials.
Hand and wrist radiographs are required to document upper limb skeletal anomalies even if clinically subtle — abnormal carpal ossification pattern is a consistent finding used to confirm diagnosis.
Cardiac evaluation including ECG (for conduction abnormalities) and echocardiogram must be current; Holter monitoring may be requested if palpitations or presyncope are reported.
TBX5 molecular confirmation is required for enrolment in most trials; de novo variants are common, so family history may be negative and should not preclude genetic testing.
Patient Resources
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