**2.5. CHARGE syndrome**

The CHARGE syndrome was previously referred as an association, however this was resolved after the discovery of causative mutations in chromodomain helicase DNA-binding gene7 (CHD7) on chromosome 8q12.1 [52, 53]. The phenotype is described by its acronym: colobomata (79%), heart defects (85%), choanal atresia (57%), growth and developmental retardation (100%), Genital hypoplasia (34%) and Ear anomalies (91%). Additional problems include renal anomalies, facial clefts and esophageal atresia [54]. CHD has been always been part of the core phenotype.

The frequency of the CHD range from 74–92% in CHD7 mutation-positive cases [55, 56], as compared to 71% in CHD7 mutation- negative individuals in one report [55]. A wide range of CHD has been reported in CHARGE syndrome, including conotruncal and aortic arch anomalies consistently over represented in clinical series [56]. The frequency of the CHARGE syndrome has been reported to range from 1 per 10,000 to 1 per 15,000 live births, although one population-based study estimated a frequency of 1 in 8500 live births [57]. Most of the cases of CHARGE syndrome are sporadic in occurrence, but autosomal dominant inheritance and germline mosaicism, have now been confirmed by molecular testing [55].
