**2.8. Holt-Oram syndrome**

The phenotype is characterized by the bilateral, asymmetrical upper limb anomalies of variable severity and is estimated to occur in 1 per 100,000 live births. There is a variation in the severity of the phenotype even within a family, and in some the upper limb anomalies may be so mild that X-ray can only diagnose them. A thumb anomaly is usually present [70]. Approximately 75% of the patients diagnosed with Holt-Oram syndrome have CHD. Atrial septal defects (secundum type) are present in 58% of these patients, in addition 28% have VSD. Up to 40% have conduction defects including a long PR interval, sinus bradycardia, atrial fibrillation and complete heart block [71]. Other types of congenital heart diseases in the form of total anomalous pulmonary venous drainage, TOF and truncus arteriosus have been associated with this syndrome [72]. There appears to be a correlation between the severity of the upper limb anomaly and the cardiac lesion [73].

Holt-Oram syndrome is an autosomal dominant condition with 100% penetrance and variable expression. New mutations make up 30–40% of the inheritance pattern. The affected gene is TBX5 on chromosome locus 12q24 [74]. The diagnosis should be considered prenatally when a cardiac lesion occurs in the presence of an upper limb anomaly. The risk to the offspring of an affected individual is 50% [61].
