Characteristic Cochlear Hypoplasia in Patients with Walker-Warburg Syndrome: A Radiologic Study of the Inner Ear in α-Dystroglycan-Related Muscular Disorders.

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.

• Authors: G Talenti, C Robson, M S Severino, C A Alves, D Chitayat, H Dahmoush, L Smith, F Muntoni, S I Blaser, F D'Arco
• Journal: AJNR. American journal of neuroradiology (AJNR Am J Neuroradiol) Vol. 42 Issue 1 Pg. 167-172 (01 2021) ISSN: 1936-959X [Electronic] United States
• PMID: 33122211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by American Journal of Neuroradiology.

Chemical References

• DAG1 protein, human
• Dystroglycans

Topics

• Adolescent
• Child
• Child, Preschool
• Cochlea (abnormalities)
• Dystroglycans (genetics)
• Female
• Humans
• Infant
• Infant, Newborn
• Magnetic Resonance Imaging (methods)
• Male
• Neuroimaging
• Phenotype
• Walker-Warburg Syndrome (complications, genetics, pathology)
• Young Adult