© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, Business Development Director GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Holt-Oram Syndrome who have limb and heart abnormalities or both.

First described in 1960 Holt-Oram Syndrome also called Heart-Hand Syndrome is usually inherited in an autosomal dominant manner and is believed to be due to a mutation on the long arm of chromosome #12 (12q24.1). 

If there is no family history until a child is born with Holt-Oram Syndrome, it is likely that the condition was due to a new mutation.  Approximately 85% are new mutations (changes) of the TBX5 gene.

The risk for each child to get the abnormal gene from an affected parent and manifest the disease could be 50%.  50% of the children would inherit the normal gene and be unaffected.

Occurrence rate is approximately 1 in 100,000 births.

Autosomal dominant inherited disorders can be variable in severity.

Upper limb abnormalities are always present in Holt-Oram Syndrome although the severity is variable, may be unilateral or bilateral and usually involve the radius, ulna and thumb. 

Approximately ¾ of these individuals have heart abnormalities most commonly an atrial septal defect. However, ventricular septal defects and arrhythmias may also be seen. 

It is recommended that a Level II ultrasound be performed at 15-22 weeks gestation to try to help rule-out upper extremities problems and a fetal echocardiogram after 22 weeks gestation to help rule-out cardiac defects.