Holt-Oram syndrome
Overview
A rare inherited disorder characterized by hand, arm and heart abnormalities. Bone abnormalities usually affect the left arm more than the right and occasionally only one arm and/or hand is affected.
Symptoms
* Absent thumbs * Underdeveloped thumbs * Triphalangeal thumbs * Split thumbs * Syndactyly * Phocomelia * Absence of first metacarpal * Absence of radius * Underdeveloped first metacarpal * Underdeveloped radius * Ulna defects * Humerus defects * Clavicle defects * Scapula defects * Sternum defects * Reduced range of elbow motion * Reduced range of shoulder motion * Narrow shoulders * Sloping shoulders * Carpal abnormalities * Underdeveloped scaphoid * Finger like thumb * Underdeveloped forearm * Ostium secundum atrial septal defect * Arrhythmia * Ventricular septal defect * Congenital heart defects * Underdeveloped arm blood vessels * Underdeveloped leg blood vessels * Carpal bone (wrist) abnormality * Missing thumb * Finger-like thumb * Partial absence of forearm bones * Complete absence of forearm bones * Underdeveloped upper arm bone * Collar bone abnormalities * Shoulder blade abnormality * Heart septum defect * Atrial septal defects * Ventricle septal defects * Heart conduction disease * Slow heart rate * Heart fibrillation
Causes
* Holt-Oram syndrome is a genetic disorder that is autosomal dominant and highly penetrant. * Initial linkage studies demonstrate that the gene defect resides on the long arm of chromosome 12. * Recent molecular genetic studies reveal that the disease is caused by mutations that inactivate the transcription factor TBX5. * Sporadic disease may represent a de novo germline mutation in TBX5. * Recognizing that individuals who present with sporadic disease may transmit the disease to offspring is important. * The identification of the role of TBX5 in Holt-Oram syndrome suggests an important but as yet undefined role for TBX5 in human cardiac septation, isomerization, and upper limb development.
Treatment
* Evaluation can usually be performed in an outpatient setting, but inpatient studies and surgical treatment may be necessary. * Patients with advanced heart block may require a permanent pacemaker. * Surgical therapy can be used to correct cardiac defects or to possibly improve limb function.