Audiological Findings in Charcot–Marie–Tooth Disease Type 4C

Abstract

OBJECTIVE:Charcot-Marie-Tooth disease type 4C (CMT4C) is a hereditary demyelinating early onset neuropathy with prominent unsteadiness and occasional cranial nerve involvement. Vestibulopathy caused by the dysfunction of cranial nerve VIII has been demonstrated in a high percentage of these patients, but the presence and degree of auditory neuropathy are unknown. The aim of the study was to characterize the hearing abnormalities of a series of patients with CMT4C and to determine the presence and severity of auditory neuropathy (AN) in these patients. MATERIALS and METHODS:Ten patients with genetically confirmed CMT4C underwent comprehensive clinical and audiological testing. The results were compared among patients in different age groups and also to the results of vestibular testing that had already been performed. RESULTS:Only 3 patients had hearing problems, but 9 had hearing abnormalities on ancillary testing that were compatible with different degrees of auditory nerve dysfunction. In the mildest cases, only the abnormality of the stapedial reflex and distortion of wave I in auditory brainstem responses could be detected. In the more severe cases, tonal audiometry revealed asymmetric hearing loss. These findings were more severe in older patients, even after correcting for age-related hypoacusia. In these patients, vestibular dysfunction could also be detected and seemed to be more profound and symmetric than hearing loss. CONCLUSION:This report confirms and defines the presence of different degrees of auditory neuropathy in all patients with CMT4C, being detectable, usually unilaterally, during infancy, and worsening with disease progression. vation of the function of outer hair cells in the cochlea; therefore, the absence of ABR demonstrates a dysfunction in the inner hair cells of the cochlea, the synapse with the auditory nerve, and/or the auditory nerve itself. A pathological examination of the cochlea in a patient with an MPZ mutation and AN revealed marked loss of auditory ganglion cells and central and peripheral auditory nerve fibers within the cochlea, with relative preservation of the cochlear hair cells [7] . Thus, the aim of the study was to characterize the hearing abnormalities in a series of patients with CMT4C and to determine the presence and severity of AN in these patients. KEYWORDS MATERIALS and METHODS SubjectsTen patients with genetically confirmed CMT4C were prospectively included in this study. Of these, 6 were males and 4 were females; cases 1 and 5 were siblings, as were cases 9 and 10. All were of Gypsy ethnicity, except cases 4 and 8 who belonged to two Caucasian families with no apparent consanguinity. Written informed consent was obtained from all patients, and the protocols were approved by the Ethics Committee of the hospital. Clinical StudyThe detailed history and complete neurological examination results were recorded. Assessment included the following: strength, muscle atrophy, sensory loss, reflexes, foot deformities, and scoliosis. Muscle strength was scored using the ...

Histopathology of the Inner Ear in Charcot-Marie-Tooth Syndrome Caused by a Missense Variant (p.Thr65Ala) in the <b><i>MPZ</i></b> Gene

“…Hearing loss has been described in CMT1A (PMP22 gene) [Alcin et al, 2000;Boerkoel et al, 2002;Kovach et al, 2002;Joo et al, 2004], in CMT1B (MPZ gene) [Starr et al, 2003], in CMTX (X-linked PRPS-1 mutations) [Synofzik et al, 2014;Gandia et al, 2015], in CMT4C [Yger et al, 2012;Sivera et al, 2017], and in CMT4B3 [Manole et al, 2017]. Vestibular abnormalities detected by electrophysiology have been described in CMT [Poretti et al, 2013].…”

“…Progressive sensorineural hearing loss has been described as part of the clinical presentation in several genetic forms of CMT, including various mutations in the MPZ gene [Chapon et al, 1999;De Jonghe et al, 1999;Alcin et al, 2000;Misu et al, 2000;Starr et al, 2003;Kochanski et al, 2004;Seeman et al, 2004;Leal et al, 2014;Tokuda et al, 2015;Duan et al, 2016], in kinships demonstrating mutations in the peripheral myelin protein (PMP22) gene [Alcin et al, 2000;Boerkoel et al, 2002;Kovach et al, 2002;Joo et al, 2004], in X-linked phosphoribosyl pyrophosphate synthetase-1 (PRPS-1) mutations [Synofzik et al, 2014;Gandia et al, 2015], and in CMT4C [Sivera et al, 2017].…”

X-Linked Sensorineural Hearing Loss: A Literature Review

“…CMTX4 is referred to as Cowchock syndrome transmitted in a recessive manner. Principal symptoms associated to this form of CMT are: hearing and sensorial loss, mental retardation, muscle weakness and axonal neuropathy [20, 21].…”

Selective Bilateral Vestibular Neuropathy in a Turkish CMT1B Family With a Novel MPZ Mutation

“…While some CMT patients have obvious hearing impairment from auditory nerve involvement, vestibular impairment will not be obvious, since the patient already has imbalance from distal weakness and somatosensory impairment. 1 Some CMT patients -CMT1B/MPZ, 2 have only auditory impairment whereas others -CMT4C/H3TC2, 3,4 or CMT4D/NDRG1 5 have severe, early impairment of both auditory and vestibular function. Here we report 12 members in 3 generations of a Turkish family with CMT1B demyelinating neuropathy due to a novel MPZ mutation, who have selective bilateral vestibular impairment with normal hearing.…”