BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for CHARGE Syndrome

DESCRIPTION

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.

POLICY

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION  

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.

SOURCES

American Academy of Pediatrics. (2013). Policy Statement: Ethical and policy issues in genetic testing and screening of children. Retrieved March 6, 2017 from www.pediatrics.org.

American College of Medical Genetics and Genomics. (2013). Technical report: ethical and policy issues in genetic testing and screening of children. Retrieved February 20, 2018 from http://www.acmg.net/docs/gim-issues_in_genetic_testing_in_children_3-2013.pdf.

BlueCross BlueShield Association. Medical Policy Reference Manual. (2:2018). Genetic testing for CHARGE syndrome (2.04.106). Retrieved February 20, 2018 from BlueWeb. (17 articles and/or guidelines reviewed)

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

ORIGINAL EFFECTIVE DATE:  2/9/2014

MOST RECENT REVIEW DATE:  3/8/2018  

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Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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