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Original Investigation
February 2017

Prevalence of Semicircular Canal Hypoplasia in Patients With CHARGE Syndrome3C Syndrome

Author Affiliations
  • 1Department of Otolaryngology, University of Cincinnati, Cincinnati, Ohio
  • 2Division of Pediatric Otolaryngology, Department of Otolaryngology, Washington University School of Medicine, St Louis, Missouri
  • 3Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri
  • 4Division of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri
  • 5Department of Otolaryngology, Oregon Health and Science University, Portland
JAMA Otolaryngol Head Neck Surg. 2017;143(2):168-177. doi:10.1001/jamaoto.2016.3175
Key Points

Question  How often do we observe anomalies of the semicircular canals in children with hearing loss and CHARGE syndrome?

Findings  In this study of medical record data, all children diagnosed as having CHARGE syndrome and with available temporal bone imaging demonstrated anomalies of the semicircular canals. These patients were diagnosed as having CHARGE either through genetic testing or dysmorphology using Verloes’ criteria.

Meaning  Anomalous development of the semicircular canals is a major criterion for CHARGE syndrome and should be emphasized by renaming the syndrome to 3C syndrome.

Abstract

Importance  CHARGE syndrome refers to a syndrome involving coloboma, heart defects, atresia choanae, retardation of growth and development, genitourinary disorders, and ear anomalies. However, Verloes revised the characteristics of CHARGE syndrome in 2005 to define this syndrome more broadly. Deficiency of the semicircular canals is now a major criterion for CHARGE syndrome.

Objective  To characterize patients with CHARGE syndrome at our center using Verloes’ criteria and to reevaluate the nomenclature for this condition.

Design, Setting, and Participants  We performed a medical chart review of patients with CHARGE syndrome and reviewed their temporal bone imaging studies at a tertiary care children’s hospital affiliated with Washington University in St Louis. Two authors independently reviewed each imaging study (A.W. and K.H.). Radiologic studies, physical findings, genetic tests, and other diagnostic tests were included. Patients with no temporal bone imaging studies were excluded.

Results  Eighteen children were included in this study; 13 children (72%) were male, and the mean (median; range) age of patients at the time of inner ear imaging studies was 2 years (4.5 years; 8 months to 8 years). Coloboma was present in 13 patients (72%) and choanal atresia in 5 (28%); semicircular canal anomalies were present in all patients. Additionally, 13 patients (72%) were diagnosed as having hindbrain anomalies, 17 (94%) as having endocrine disorders, 17 (94%) as having mediastinal organ malformations, and all as having middle or external ear abnormalities and development delay. Cleft lip and cleft palate were found in 6 of 14 patients (43%) who did not have choanal atresia. We tested 16 patients for mutations in the CHD7 gene; 10 were positive (63%) for mutations, 4 (25%) were negative, and 2 (13%) were inconclusive.

Conclusions and Relevance  Semicircular canal anomalies were the most consistent finding in our patients with CHARGE syndrome. Given the high prevalence of semicircular canal hypoplasia and importance of imaging for diagnosing CHARGE syndrome, we propose changing the term CHARGE syndrome to 3C syndrome to emphasize the importance of the semicircular canals and to recall the 3 major criteria for diagnosis: coloboma, choanal atresia, and semicircular canal anomaly. The nomenclature would also reference the 3 semicircular canals in each ear. This new name for CHARGE syndrome would provide a mnemonic and focus the disease on the most important clinical criteria for diagnosis.

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