Rare Disease : CHARGE SYNDROME

CHARGE syndrome is an autosomal dominant congenital and rare genetic disease involving Coloboma, Heart defects, Choanal Atresia, Retarded growth and development, Genital hypoplasia, Ear anomalies and/or deafness (1)(2). The prevalence of this syndrome varies between 1/8,500 to 1/12,000 live birth in Europe and Canada (3).

Table 1. Diagnostic criteria for CHARGE syndrome (4)(5)(6)

	Verloes (2005) updated by Blake (2006)	Hale (2016)
Major criteria	-          Coloboma; -          Choanal atresia and/or cleft lip or palate; -          Semicircular canals agenesis/ hypoplasia; -          Arhinencephaly and/or anosmia	-          Coloboma; -          Choanal atresia and/or cleft lip or palate; -          Abnormal external, middle or inner ears, including hypoplastic semicircular canals; -          Pathogenic CHD7 variant
Minor Criteria	-          Cranial nerves VII to XII dysfunction; -          Hypothalamo-hypophyseal dysfunction; -          External- or middle-ear anomalies; -          Heart defect or esophageal anomalies; -          Intellectual disability	-          Cranial nerve dysfunction including hearing loss; -          Dysphagia/feeding difficulties; -          Structural brain anomalies; -          Developmental delay/intellectual disabilities/autism; -          Hypothalamo-hypophyseal dysfunction (gonadotropin or growth hormone deficiency ) and genital anomalies; -          Heart or esophagus malformation; -          Renal anomalies -          Skeletal/limb anomalies
	Typical: (3 major) or (2 major + at least 2 minor) criteria; Partial: 2 major + 1 minor criteria; Atypical: (2 major + 0 minor) or (1 major + 3 minor criteria)	2 major + any number of minor criteria

Clinical diagnostic criteria for CHARGE Syndrome were proposed in 1998 and revised in 2005 by Verloes. Semi circular-canal (SCC) hypoplasia was added to the major criteria and a classification of typical, partial, and atypical forms was proposed (4). Then, cleft palate was suggested to replace choanal atresia when absent by Blake and Prasad (2006) (5). A variant pathogenic CHD7 gene was later added to the major features of charge syndrome (Table 1) (6).

References

1.     Jongmans MC, Admiraal, R.J., van der Donk KP, Vissers LE, Baas AF, Kapusta L, et al. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. 2006;43:306–14.

2.     Tellier A., Cormier-Daire V, Abadie V, Amiel J, Sigaudy S, Bonnet D, et al. CHARGE syndrome: Report of 47 cases and review. Am J Med Genet. 1998;76(5):402–9.

3.    Issekutz KA, Jr JMG, Prasad C, Smith IM, Blake KD. An Epidemiological Analysis of CHARGE Syndrome : Preliminary Results From a Canadian Study. 2005;317(December 2003):309–17.

4.        Verloes A. Updated diagnostic criteria for CHARGE syndrome: A proposal. Am J Med Genet. 2005;133 A(3):306–8.

5.        Blake KD, Prasad C. CHARGE syndrome. Orphanet J Rare Dis. 2006;42(2):101–2.

6.         Hale CL, Niederriter AN, Green GE, Martin DM. Atypical phenotypes associated with             pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria. HHS Public Access. 2017;(2):344–54.