1999-05-17-15 Holt-Oram syndrome © Jeanty /www.thefetus.net/
Philippe Jeanty, MD, PhD & Sandra R Silva, MD
Definition: The Holt-Oram syndrome consists of congenital heart disease and anomalies of the upper limb (phocomelia (4.5%), radial ray aplasia, triphalangeal thumb, clinodactyly).
Synonyms: Heart-hand syndrome. (This syndrome appears genetically distinct from the Heart-hand syndrome Type II and III).
Etiology: Autosomal dominant with 100% penetrance and no evidence of reduced fitness. Increasing severity occurs in succeeding generations consistent with anticipation1.
Recurrence risk: 50%.
Diagnosis: The cardiac lesions include atrio (30-60%) and ventricular septal defects (fig. 1), patent ductus arteriosus, endocardial cushion defect, hypoplasia of the left ventricle and conduction disturbances. 17% have complex cardiac anomalies. The radial ray aplasia varies from a difficult to diagnose triphalangeal thumb to more obvious club hand. The absence of the thumb can also be recognized.
Figure 1: 1.3 mm VSD
Figure 2: A coronal view of the 4-digit hand.
Figure 3: The four digits of the hand are seen. The radial side is well visible (lower left side of the image) and the thumb is clearly absent.
Figure 4: On the other hand, a small skin tag is present at the place of the thumb (arrow).
Pathogenesis: Probable cardiomelic developmental field.
Genetic anomaly: Mutations in two of the T-box genes (TBX5 and TBX3) on chromosome 12q24.1 have been shown to be responsible for the congenital abnormalities associated with Holt Oram syndrome,,. TBX5 is only involved in anterior limb development
Associated anomalies: See definition. A few inconstant anomalies such as renal anomalies have been reported too.
Differential diagnosis: The differential is usually that of the radial ray aplasia and could include the TAR syndrome, Fanconi anemia, VACTERL association, and the radial ray-choanal atresia.
Prognosis: Mainly related to the severity of the cardiac and orthopedic handicap.
Management: Usually no alteration of the prenatal care is needed. Great orthopedic progresses at pollicisation of the index finger to provide opposition have decreased the handicap of some of these children.
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