G Talenti1, C Robson2, M S Severino3, C A Alves4, D Chitayat5, H Dahmoush6, L Smith7, F Muntoni8, S I Blaser9, F D'Arco10. 1. From the Department of Diagnostics and Pathology (G.T.), Neuroradiology Unit, Verona University Hospital, Verona, Italy. 2. Division of Neuroradiology (C.R.), Department of Radiology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts. 3. Neuroradiology Unit (M.S.S.), Istituti di Ricovero e Cura a Carattere Scientifico, Istituto Giannina Gaslini, Genova, Italy. 4. Departments of Radiology and Division of Neuroradiology (C.A.A.), Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 5. The Prenatal Diagnosis and Medical Genetics Program (D.C.), Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. 6. Department of Radiology (H.D.), Lucile Packard Children's Hospital, Stanford University School of Medicine, Stanford, California. 7. Dental and Maxillofacial Surgery Department (L.S.), Great Ormond Street Hospital, London, UK. 8. Dubowitz Neuromuscular Centre (F.M.), UCL Great Ormond Street Institute of Child Health and Great Ormond Street Hospital, London, UK. 9. Division of Neuroradiology (S.I.B.), Department of Diagnostic Imaging, The Hospital for Sick Children, Toronto, Ontario, Canada. 10. Neuroradiology Unit (F.D.), Department of Radiology, Great Ormond Street Hospital for Children, National Health Service Trust, London, UK felice.d'arco@gosh.nhs.uk.
Abstract
BACKGROUND AND PURPOSE: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan-related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric hospitals and reported the radiologic features and frequency of inner ear dysplasias. MATERIALS AND METHODS: Patients previously diagnosed clinicoradiologically with Walker-Warburg syndrome, muscle-eye-brain disease, or Fukuyama congenital muscular dystrophy were included. We recorded the pathogenic variant, when available. Brain MR imaging and/or CT findings were reviewed in consensus, and inner ear anomalies were classified according to previous description in the literature. We then correlated the clinicoradiologic phenotype with the inner ear phenotype. RESULTS: Thirteen patients fulfilled the criteria for the Walker-Warburg syndrome phenotype, 8 for muscle-eye-brain disease, and 3 for Fukuyama congenital muscular dystrophy. A dysplastic cochlea was demonstrated in 17/24. The most frequent finding was a pronounced cochlear hypoplasia type 4 with a very small anteriorly offset turn beyond the normal-appearing basal turn (12/13 patients with Walker-Warburg syndrome and 1/11 with muscle-eye-brain disease or Fukuyama congenital muscular dystophy). Two of 8 patients with muscle-eye-brain disease, 1/3 with Fukuyama congenital muscular dystrophy, and 1/13 with Walker-Warburg syndrome showed a less severe cochlear hypoplasia type 4. The remaining patients without Walker-Warburg syndrome were healthy. The vestibule and lateral semicircular canals of all patients were normal. Cranial nerve VIII was present in all patients with diagnostic MR imaging. CONCLUSIONS: Most patients with the severe α-dystroglycanopathy Walker-Warburg syndrome phenotype have a highly characteristic cochlear hypoplasia type 4. Patients with the milder variants, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, more frequently have a normal cochlea or milder forms of hypoplasia.
BACKGROUND AND PURPOSE: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan-related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric hospitals and reported the radiologic features and frequency of inner ear dysplasias. MATERIALS AND METHODS: Patients previously diagnosed clinicoradiologically with Walker-Warburg syndrome, muscle-eye-brain disease, or Fukuyama congenital muscular dystrophy were included. We recorded the pathogenic variant, when available. Brain MR imaging and/or CT findings were reviewed in consensus, and inner ear anomalies were classified according to previous description in the literature. We then correlated the clinicoradiologic phenotype with the inner ear phenotype. RESULTS: Thirteen patients fulfilled the criteria for the Walker-Warburg syndrome phenotype, 8 for muscle-eye-brain disease, and 3 for Fukuyama congenital muscular dystrophy. A dysplastic cochlea was demonstrated in 17/24. The most frequent finding was a pronounced cochlear hypoplasia type 4 with a very small anteriorly offset turn beyond the normal-appearing basal turn (12/13 patients with Walker-Warburg syndrome and 1/11 with muscle-eye-brain disease or Fukuyama congenital muscular dystophy). Two of 8 patients with muscle-eye-brain disease, 1/3 with Fukuyama congenital muscular dystrophy, and 1/13 with Walker-Warburg syndrome showed a less severe cochlear hypoplasia type 4. The remaining patients without Walker-Warburg syndrome were healthy. The vestibule and lateral semicircular canals of all patients were normal. Cranial nerve VIII was present in all patients with diagnostic MR imaging. CONCLUSIONS: Most patients with the severe α-dystroglycanopathy Walker-Warburg syndrome phenotype have a highly characteristic cochlear hypoplasia type 4. Patients with the milder variants, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, more frequently have a normal cochlea or milder forms of hypoplasia.
Authors: Peter B Kang; Leslie Morrison; Susan T Iannaccone; Robert J Graham; Carsten G Bönnemann; Anne Rutkowski; Joseph Hornyak; Ching H Wang; Kathryn North; Maryam Oskoui; Thomas S D Getchius; Julie A Cox; Erin E Hagen; Gary Gronseth; Robert C Griggs Journal: Neurology Date: 2015-03-31 Impact factor: 9.910
Authors: Felice D'Arco; Eser Sanverdi; William T O'Brien; Ajay Taranath; Giacomo Talenti; Susan I Blaser Journal: Neuroradiology Date: 2020-03-03 Impact factor: 2.804
Authors: W B Dobyns; R A Pagon; D Armstrong; C J Curry; F Greenberg; A Grix; L B Holmes; R Laxova; V V Michels; M Robinow Journal: Am J Med Genet Date: 1989-02