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.
