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DOI: 10.1055/s-0029-1241035
Bilateral Vestibulopathy: Clinical, Diagnostic, and Genetic Considerations
Publication History
Publication Date:
15 October 2009 (online)
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ABSTRACT
Bilateral vestibulopathy is a rare, but important cause of imbalance that is underrecognized and not well understood. Clinically heterogeneous, it is variably associated with recurrent vertigo, hearing loss, migraine, peripheral neuropathy, or cerebellar degeneration. In about half of all patients with bilateral vestibulopathy, no cause can be identified. There have been several reports of familial bilateral vestibulopathy, suggesting genetic predisposition. The identification of genetic defects underlying hereditary deafness syndromes has greatly advanced the understanding of the functional components and the development of cochlea. In contrast, the progress in bilateral vestibulopathy has been slow, likely hampered by the difficulty in diagnosis outside of academic centers and a lack of animal models that recapitulate the progressive clinical features that are not apparent from birth. It is reasonable to anticipate that there will be an equally large number of genetic disorders underlying bilateral vestibulopathy as in deafness. Understanding the pathophysiology of bilateral vestibulopathy may suggest possible causes for the gradual decline in vestibular function that occurs with normal aging. Furthermore, the study of bilateral vestibulopathy may shed light on the pathophysiology of more common vestibular syndromes such as benign recurrent vertigo and vestibular migraine.
KEYWORDS
Vestibulopathy - idiopathic - hereditary
REFERENCES
- 1 Leigh R J, Thurtell M. Vestibular areflexia: under the radar. Ann Neurol. 2007; 61(6) 499-500
- 2 Baloh R W, Jacobson K, Honrubia V. Idiopathic bilateral vestibulopathy. Neurology. 1989; 39(2 Pt 1) 272-275
- 3 Zingler V C, Cnyrim C, Jahn K et al.. Causative factors and epidemiology of bilateral vestibulopathy in 255 patients. Ann Neurol. 2007; 61(6) 524-532
- 4 Baloh R W, Jacobson K, Fife T. Familial vestibulopathy: a new dominantly inherited syndrome. Neurology. 1994; 44(1) 20-25
- 5 Brantberg K. Familial early-onset progressive vestibulopathy without hearing impairment. Acta Otolaryngol. 2003; 123(6) 713-717
- 6 Jen J C, Wang H, Lee H et al.. Suggestive linkage to chromosome 6q in families with bilateral vestibulopathy. Neurology. 2004; 63(12) 2376-2379
- 7 Jen J, Baloh R H, Ishiyama A, Baloh R W. Dejerine-Sottas syndrome and vestibular loss due to a point mutation in the PMP22 gene. J Neurol Sci. 2005; 237(1-2) 21-24
- 8 Migliaccio A A, Halmagyi G M, McGarvie L A, Cremer P D. Cerebellar ataxia with bilateral vestibulopathy: description of a syndrome and its characteristic clinical sign. Brain. 2004; 127(Pt 2) 280-293
- 9 Baloh R H, Honrubia V. Clinical Neurophysiology of the Vestibular System. 3rd ed. New York; Oxford University Press 2001
- 10 Baloh R W, Honrubia V, Yee R D, Hess K. Changes in the human vestibulo-ocular reflex after loss of peripheral sensitivity. Ann Neurol. 1984; 16(2) 222-228
- 11 Welgampola M S, Colebatch J G. Characteristics and clinical applications of vestibular-evoked myogenic potentials. Neurology. 2005; 64(10) 1682-1688
- 12 Matsuzaki M, Murofushi T. Vestibular evoked myogenic potentials in patients with idiopathic bilateral vestibulopathy. Report of three cases. ORL J Otorhinolaryngol Relat Spec. 2001; 63(6) 349-352
- 13 Fujimoto C, Iwasaki S, Matsuzaki M, Murofushi T. Lesion site in idiopathic bilateral vestibulopathy: a galvanic vestibular-evoked myogenic potential study. Acta Otolaryngol. 2005; 125 430-432
- 14 Halmagyi G M, Curthoys I S. A clinical sign of canal paresis. Arch Neurol. 1988; 45(7) 737-739
- 15 Beynon G J, Jani P, Baguley D M. A clinical evaluation of head impulse testing. Clin Otolaryngol Allied Sci. 1998; 23(2) 117-122
- 16 Schubert M C, Das V, Tusa R J, Herdman S J. Cervico-ocular reflex in normal subjects and patients with unilateral vestibular hypofunction. Otol Neurotol. 2004; 25(1) 65-71
- 17 Ramat S, Zee D S, Minor L B. Translational vestibulo-ocular reflex evoked by a “head heave” stimulus. Ann N Y Acad Sci. 2001; 942 95-113
- 18 Kessler P, Tomlinson D, Blakeman A et al.. The high-frequency/acceleration head heave test in detecting otolith diseases. Otol Neurotol. 2007; 28 896-904
- 19 Baloh R W, Lopez I, Beykirch K, Ishiyama A, Honrubia V. Clinical-pathologic correlation in a patient with selective loss of hair cells in the vestibular endorgans. Neurology. 1997; 49(5) 1377-1382
- 20 Van Camp G, Smith R J. The hereditary hearing loss homepage. Available at: http://webh01.ua.ac.be/hhh/ Accessed April 9, 2009
- 21 Smith R J, Van Camp G. Deafness and hereditary hearing loss overview. GeneReviews (Review) 2008. Available at: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=deafness-overview Accessed April 9, 2009
- 22 Morton C C, Nance W E. Newborn hearing screening—a silent revolution. N Engl J Med. 2006; 354(20) 2151-2164
- 23 Schrijver I, Gardner P. Hereditary sensorineural hearing loss: advances in molecular genetics and mutation analysis. Expert Rev Mol Diagn. 2006; 6(3) 375-386
- 24 Robertson N G, Lu L, Heller S et al.. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nat Genet. 1998; 20(3) 299-303
- 25 Tamagawa Y, Ishikawa K, Ishikawa K et al.. Phenotype of DFNA11: a nonsyndromic hearing loss caused by a myosin VIIA mutation. Laryngoscope. 2002; 112(2) 292-297
- 26 Fransen E, Verstreken M, Verhagen W I et al.. High prevalence of symptoms of Menière's disease in three families with a mutation in the COCH gene. Hum Mol Genet. 1999; 8(8) 1425-1429
- 27 Sanchez E, López-Escámez J A, López-Nevot M A, López-Nevot A, Cortes R, Martin J. Absence of COCH mutations in patients with Meniere disease. Eur J Hum Genet. 2004; 12(1) 75-78
- 28 Brown M. Ménière's's syndrome. Arch Neurol Psychiatry. 1941; 46 561-565
- 29 Bernstein J M. Occurrence of episodic vertigo and hearing loss in families. Ann Otol Rhinol Laryngol. 1965; 74(4) 1011-1021
- 30 Birgerson L, Gustavson K H, Stahle J. Familial Menière's disease: a genetic investigation. Am J Otol. 1987; 8(4) 323-326
- 31 Morrison A W. Anticipation in Menière's disease. J Laryngol Otol. 1995; 109(6) 499-502
- 32 Oliveira C A, Ferrari I, Messias C I. Occurrence of familial Meniere's syndrome and migraine in Brasília. Ann Otol Rhinol Laryngol. 2002; 111(3 Pt 1) 229-236
- 33 Frykholm C, Larsen H C, Dahl N, Klar J, Rask-Andersen H, Friberg U. Familial Ménière's's disease in five generations. Otol Neurotol. 2006; 27(5) 681-686
- 34 Klockars T, Kentala E. Inheritance of Meniere's disease in the Finnish population. Arch Otolaryngol Head Neck Surg. 2007; 133(1) 73-77
- 35 Neuhauser H, Leopold M, von Brevern M, Arnold G, Lempert T. The interrelations of migraine, vertigo, and migrainous vertigo. Neurology. 2001; 56(4) 436-441
- 36 Radtke A, Lempert T, Gresty M A, Brookes G B, Bronstein A M, Neuhauser H. Migraine and Ménière's's disease: is there a link?. Neurology. 2002; 59(11) 1700-1704
- 37 Morrison A W, Johnson K J. Genetics (molecular biology) and Meniere's disease. Otolaryngol Clin North Am. 2002; 35(3) 497-516
- 38 Klar J, Frykholm C, Friberg U, Dahl N A. Meniere's disease gene linked to chromosome 12p12.3 Am J Med Genet B Neuropsychiatr Genet. 2006; 141B 463-467
- 39 Verhagen W I, Huygen P L, Horstink M W. Familial congenital vestibular areflexia. J Neurol Neurosurg Psychiatry. 1987; 50(7) 933-935
- 40 Leibovici M, Safieddine S, Petit C. Mouse models for human hereditary deafness. Curr Top Dev Biol. 2008; 84 385-429
- 41 Whitfield T T. Zebrafish as a model for hearing and deafness. J Neurobiol. 2002; 53(2) 157-171
- 42 Whitfield T T, Granato M, van Eeden F J et al.. Mutations affecting development of the zebrafish inner ear and lateral line. Development. 1996; 123 241-254
- 43 Nicolson T. The genetics of hearing and balance in zebrafish. Annu Rev Genet. 2005; 39 9-22
- 44 Paffenholz R, Bergstrom R A, Pasutto F et al.. Vestibular defects in head-tilt mice result from mutations in Nox3, encoding an NADPH oxidase. Genes Dev. 2004; 18(5) 486-491
- 45 Hurle B, Ignatova E, Massironi S M et al.. Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1. Hum Mol Genet. 2003; 12(7) 777-789
- 46 Huang L, Kuo Y M, Gitschier J. The pallid gene encodes a novel, syntaxin 13-interacting protein involved in platelet storage pool deficiency. Nat Genet. 1999; 23(3) 329-332
- 47 Swank R T, Reddington M, Howlett O, Novak E K. Platelet storage pool deficiency associated with inherited abnormalities of the inner ear in the mouse pigment mutants muted and mocha. Blood. 1991; 78(8) 2036-2044
- 48 Zhang Q, Li W, Novak E K et al.. The gene for the muted (mu) mouse, a model for Hermansky-Pudlak syndrome, defines a novel protein which regulates vesicle trafficking. Hum Mol Genet. 2002; 11(6) 697-706
- 49 Huang L, Gitschier J. A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet. 1997; 17(3) 292-297
- 50 Nakano Y, Longo-Guess C M, Bergstrom D E, Nauseef W M, Jones S M, Bánfi B. Mutation of the Cyba gene encoding p22phox causes vestibular and immune defects in mice. J Clin Invest. 2008; 118(3) 1176-1185
- 51 Cryns K, Van Spaendonck M P, Flothmann K et al.. Vestibular dysfunction in the epistatic circler mouse is caused by phenotypic interaction of one recessive gene and three modifier genes. Genome Res. 2002; 12(4) 613-617
- 52 Pau H, Hawker K, Fuchs H, De Angelis M H, Steel K P. Characterization of a new mouse mutant, flouncer, with a balance defect and inner ear malformation. Otol Neurotol. 2004; 25(5) 707-713
Joanna C JenM.D. Ph.D.
David Geffen School of Medicine at UCLA
710 Westwood Plaza, Los Angeles, CA 90095-1769
Email: jjen@ucla.edu