BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for CHARGE Syndrome


CHARGE syndrome is a rare genetic condition associated with multiple congenital anomalies. The letters of CHARGE syndrome corresponds to clinical features: C = ocular Coloboma, H = Heart defect, A = Atresia choanae, R = Retarded growth and development, G = Genital hypoplasia and E = Ear anomalies/deafness. However, a number of other malformations are also common in this condition. In particular, hypoplasia of the semi-circular canals has emerged as a frequent and distinctive CHARGE malformation. The condition is caused by mutations of the CHD7 gene on chromosome 8q12.1. CHD7 is the only gene currently known to be associated with CHARGE syndrome.

In many individuals, the diagnosis can be made based on clinical findings. However, the phenotype of the disease is highly variable, and some patients do not fulfill all the criteria for diagnosis by clinical findings. Major characteristics include ocular coloboma, choanal atresia or stenosis, cranial nerve abnormality, ear anomalies or deafness. Minor characteristics include genital hypoplasia, hypogonadotrophic hypogonadism, developmental delays, cardiac malformations, short stature, cleft lip and/or cleft palate, tracheoesophageal fistula, and distinctive CHARGE facial appearance, which consist of a prominent forehead and a prominent nasal bridge. Other, less frequent manifestations include kidney malformations, immunodeficiency, various limb abnormalities, scoliosis, dental problems, omphalocele, brain malformations, attention deficit hyperactivity disorder (ADHD), and various behavioral problems.

Most instances of CHARGE syndrome are sporadic events in a family and appear to be caused by de novo CHD7 mutations, but on rare occasions CHARGE can be inherited as an autosomal dominant condition. Recurrence in siblings because of germline mosaicism has also been reported. The prevalence of CHARGE syndrome is estimated at 1 in 8,500 live births.





A diagnosis of definite CHARGE syndrome can be made clinically in individuals with all four major characteristics or three major and three minor characteristics. In patients without the classical clinical criteria to diagnose CHARGE, in those with a milder phenotype, and/or in those with features that overlap with and cannot be distinguished from other syndromes, genetic testing may provide a definitive diagnosis.


American Academy of Pediatrics (2013) Policy Statement: Ethical and Policy Issues in Genetic Testing and Screening of Children. Retrieved March 6, 2017 from:

Bartels, C., F., Scacheri, C., White, L., Scacheri, P. C., & Bale, S. (2010). Mutations in the CHD7 gene: the experience of a commercial laboratory. Genetic Testing and Molecular Biomarkers, 14 (6), 881-892. (Level 3 evidence)

Blake, K., Ravenswaaij, C., Hoefsloot, L., & Verloes, A. (March 2011). Clinical utility gene card for: CHARGE syndrome. European Journal of Human Genetics (2011) 19; doi:10.1038/ejhg.2011.45. (Level 4 evidence)

BlueCross BlueShield Association. Medical Policy Reference Manual. (2017, February). Genetic testing for CHARGE syndrome (2.04.106). Retrieved March 6, 2017 from BlueWeb. (18 articles and/or guidelines reviewed)

Lalani S.R., Hefner, M.A., Belmont, J.W., & Davenport, S.L. (2006, October, updated 2012, February). CHARGE Syndrome. Retrieved September 19, 2013 from . (Level 5 evidence)

Ravenswaaij, C., Blake, K., Hoefsloot, L., and Verloes, A. (2015, February) Clinical utility gene card for: CHARGE syndrome - update 2015. European Journal of Human Genetics (2015) 23. (Level 4 evidence)

Winifred S. Hayes, Inc. Genetic Test Evaluation (GTE) Report. (2014, September). CHARGE Syndrome. Retrieved April 27, 2016 from (51 articles and/or guidelines reviewed)




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