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Comment & Response
June 2017

Support for the Diagnosis of CHARGE Syndrome

Author Affiliations
  • 1Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
  • 2IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada
  • 3Departments of Pediatrics and Communicable Diseases and of Human Genetics, University of Michigan Medical School, Ann Arbor
JAMA Otolaryngol Head Neck Surg. 2017;143(6):634-635. doi:10.1001/jamaoto.2016.4762

To the Editor We read the recently published article “Prevalence of Semicircular Canal Hypoplasia in Patients with CHARGE Syndrome: 3C Syndrome” by Wineland et al,1 wherein the authors presented a chart review and clinical features of 18 patients with CHARGE syndrome, and concluded that the most consistent clinical finding in their cohort was semicircular canal anomalies. They also proposed that a new name (“3C syndrome”) be used instead of CHARGE syndrome to describe this complex multiple anomaly condition. Several important issues are raised by this study which deserve attention. First, the observations described in the article are not novel; rather, they support previous publications which (a) demonstrate the high prevalence of inner ear malformations in individuals with CHARGE syndrome and (b) propose inclusion of temporal bone CT and MRI in the evaluation of individuals who have features of CHARGE syndrome.2 Second, the authors claim that fluorescent in situ hybridization (FISH) studies excluded mutations in CHD7. Importantly, FISH only excludes genomic deletions or duplications and does not evaluate for CHD7 sequence changes, which comprise most mutations in individuals with CHARGE.2 Third, the proposal 3C syndrome as a new acronym for CHARGE is misguided. In 2007, Sanlaville and Verloes3 discussed the “3C triad” of features in CHARGE, which, together with arhinencephaly and rhombencephalic dysfunctions, are considered the most important and constant clues to the diagnosis. Sanlaville and Verloes did not propose replacing the acronym CHARGE with “3C”, probably because 3C syndrome is a term already used to describe cranio-cerebello-cardiac syndrome (also called Ritscher-Schinzel Syndrome), a completely separate entity4 with its own Online Mendelian Inheritance in Man number (220210) and 24 current citations in Pubmed. Finally, and perhaps most importantly, the term CHARGE has been broadly used since 1981 to describe individuals with a constellation of clinical features including coloboma of the eyes, heart disease, atresia of the choanae, retardation of growth and development, genital hypoplasia including pubertal delay, and ear abnormalities with deafness and vestibular dysfunction. The term CHARGE captures the variable clinical expressivity observed in this condition, and the term has been embraced by affected individuals, their families, and the public. If the authors’ intention was to simplify the diagnostic approach to individuals with features of CHARGE, they should review a recent study of major diagnostic criteria and testing options that emphasizes inner ear malformations and CHD7 molecular genetic testing.5

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