BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for CHARGE Syndrome

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018


CHARGE syndrome is a rare genetic condition associated with multiple congenital anomalies. The letters of CHARGE syndrome correspond 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. There are other malformations 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. Since the phenotype of the disease is highly variable, some individuals 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 individuals 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.


BlueCross BlueShield Association. Evidence Positioning System. (3:2021). Genetic testing for CHARGE syndrome (2.04.106). Retrieved June 11, 2021 from (16 articles and/or guidelines reviewed) Centers for Medicare & Medicaid Services. Palmetto GBA. (2019, October). Local Coverage Article: Billing and Coding: MolDX: CHD7 gene analysis A53565. Retrieved June 11, 2021 from

Legendre, M., Abadie, V., Attié-Bitach, T., Philip, N., Busa, T., Bonneau, D., et al. Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome. American Journal of Medical Genetics, 175 (4), 417–430. Abstract retrieved November 22, 2019 from PubMed database.

van Ravenswaaij-Arts, C.M., Blake, K., Hoefsloot, L., & Verloes, A. (2015). Clinical utility gene card for: CHARGE syndrome - update 2015. European Journal of Human Genetics, 23 (11), doi:10.1038/ejhg.2015.15 (Level 2 evidence)




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