Prevalence of semicircular canal hypoplasia in patients with charge syndrome 3c syndrome

Andre Wineland, Maithilee D. Menezes, Joshua S. Shimony, Marwan S. Shinawi, Timothy Hullar, Keiko Hirose

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 withWashington 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 anomalieswere 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.

Original languageEnglish (US)
Pages (from-to)168-177
Number of pages10
JournalJAMA Otolaryngology - Head and Neck Surgery
Volume143
Issue number2
DOIs
StatePublished - Feb 1 2017

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CHARGE Syndrome
Semicircular Canals
Choanal Atresia
Coloboma
Temporal Bone
Terminology
Ear
3C syndrome
External Ear
Rhombencephalon
Mutation
Nasopharynx
Cleft Lip
Cleft Palate
Middle Ear
Inner Ear
Tertiary Healthcare
Growth and Development
Routine Diagnostic Tests
Names

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

Cite this

Prevalence of semicircular canal hypoplasia in patients with charge syndrome 3c syndrome. / Wineland, Andre; Menezes, Maithilee D.; Shimony, Joshua S.; Shinawi, Marwan S.; Hullar, Timothy; Hirose, Keiko.

In: JAMA Otolaryngology - Head and Neck Surgery, Vol. 143, No. 2, 01.02.2017, p. 168-177.

Research output: Contribution to journalArticle

Wineland, Andre ; Menezes, Maithilee D. ; Shimony, Joshua S. ; Shinawi, Marwan S. ; Hullar, Timothy ; Hirose, Keiko. / Prevalence of semicircular canal hypoplasia in patients with charge syndrome 3c syndrome. In: JAMA Otolaryngology - Head and Neck Surgery. 2017 ; Vol. 143, No. 2. pp. 168-177.
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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 withWashington 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 anomalieswere 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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AU - Hullar, Timothy

AU - Hirose, Keiko

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N2 - 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 withWashington 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 anomalieswere 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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