J Pao1, F D'Arco2, E Clement3, S Picariello4,5, G Moonis6, C D Robson7, A F Juliano8. 1. From the Department of Radiology (J.P.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. 2. Department of Radiology (F.D.). 3. Department of Clinical Genetics (E.C.), Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. 4. Department of Women, Child and General and Specialized Surgery (S.P.), University of Campania "Luigi Vanvitelli," Naples, Italy. 5. Department of Paediatric Oncology (S.P.), Neuro-Oncology Unit, Santobono-Pausilipon Children's Hospital, Naples, Italy. 6. Department of Radiology (G.M.), Columbia University Irving Medical Center, New York, New York. 7. Department of Radiology (C.D.R.), Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts. 8. Department of Radiology (A.F.J.), Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts amy_juliano@meei.harvard.edu.
Abstract
BACKGROUND AND PURPOSE: Temporal bone imaging plays an important role in the work-up of branchio-oto-renal syndrome. Previous reports have suggested that the unwound or offset cochlea is a highly characteristic marker for branchio-oto-renal syndrome. Our goals were to examine the prevalence of this finding in a branchio-oto-renal syndrome cohort and analyze genetic-phenotypic associations not previously established. MATERIALS AND METHODS: This multicenter retrospective study included 38 ears in 19 unrelated individuals with clinically diagnosed branchio-oto-renal syndrome and confirmed mutations in the EYA1 or SIX1 genes. Two blinded neuroradiologists independently reviewed and documented temporal bone imaging findings in 13 categories for each ear. Imaging phenotypes were correlated with genotypes. RESULTS: There was excellent interrater agreement for all 13 phenotypic categories (κ ≥ 0.80). Of these, 9 categories showed statistically significant differences between patients with EYA1-branchio-oto-renal syndrome and SIX1-branchio-oto-renal syndrome. Cochlear offset was present in 100% of patients with EYA1-branchio-oto-renal syndrome, but in only 1 ear (12.5%) among patients with SIX1-branchio-oto-renal syndrome. A short thorny appearance of the cochlear apical turn was observed in most patients with SIX1-branchio-oto-renal syndrome. CONCLUSIONS: An offset cochlea is associated with the EYA1-branchio-oto-renal syndrome genotype. The SIX1-branchio-oto-renal syndrome genotype is associated with a different cochlear phenotype that almost always is without offset and has a short thorny tip as the apical turn. Therefore, cochlear offset is not a characteristic marker for all patients with branchio-oto-renal syndrome. The lack of a cochlear offset in a patient with clinically suspected branchio-oto-renal syndrome does not exclude the diagnosis and, in fact, may be predictive of the SIX1 genotype.
BACKGROUND AND PURPOSE: Temporal bone imaging plays an important role in the work-up of branchio-oto-renal syndrome. Previous reports have suggested that the unwound or offset cochlea is a highly characteristic marker for branchio-oto-renal syndrome. Our goals were to examine the prevalence of this finding in a branchio-oto-renal syndrome cohort and analyze genetic-phenotypic associations not previously established. MATERIALS AND METHODS: This multicenter retrospective study included 38 ears in 19 unrelated individuals with clinically diagnosed branchio-oto-renal syndrome and confirmed mutations in the EYA1 or SIX1 genes. Two blinded neuroradiologists independently reviewed and documented temporal bone imaging findings in 13 categories for each ear. Imaging phenotypes were correlated with genotypes. RESULTS: There was excellent interrater agreement for all 13 phenotypic categories (κ ≥ 0.80). Of these, 9 categories showed statistically significant differences between patients with EYA1-branchio-oto-renal syndrome and SIX1-branchio-oto-renal syndrome. Cochlear offset was present in 100% of patients with EYA1-branchio-oto-renal syndrome, but in only 1 ear (12.5%) among patients with SIX1-branchio-oto-renal syndrome. A short thorny appearance of the cochlear apical turn was observed in most patients with SIX1-branchio-oto-renal syndrome. CONCLUSIONS: An offset cochlea is associated with the EYA1-branchio-oto-renal syndrome genotype. The SIX1-branchio-oto-renal syndrome genotype is associated with a different cochlear phenotype that almost always is without offset and has a short thorny tip as the apical turn. Therefore, cochlear offset is not a characteristic marker for all patients with branchio-oto-renal syndrome. The lack of a cochlear offset in a patient with clinically suspected branchio-oto-renal syndrome does not exclude the diagnosis and, in fact, may be predictive of the SIX1 genotype.
Authors: Xue Li; Kenneth A Oghi; Jie Zhang; Anna Krones; Kevin T Bush; Christopher K Glass; Sanjay K Nigam; Aneel K Aggarwal; Richard Maas; David W Rose; Michael G Rosenfeld Journal: Nature Date: 2003-11-20 Impact factor: 49.962
Authors: Rainer G Ruf; Pin-Xian Xu; Derek Silvius; Edgar A Otto; Frank Beekmann; Ulla T Muerb; Shrawan Kumar; Thomas J Neuhaus; Markus J Kemper; Richard M Raymond; Patrick D Brophy; Jennifer Berkman; Michael Gattas; Valentine Hyland; Eva-Maria Ruf; Charles Schwartz; Eugene H Chang; Richard J H Smith; Constantine A Stratakis; Dominique Weil; Christine Petit; Friedhelm Hildebrandt Journal: Proc Natl Acad Sci U S A Date: 2004-05-12 Impact factor: 11.205