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The most common type of hereditary motor and sensory neuropathy type 1, HMSN 1A, is caused by a duplication of the gene for peripheral myelin protein 22 (PMP 22), situated on chromosome 17p. We report on a patient with this genotype with bilateral sensorineural deafness.
A 28 year old man presented with progressive distal weakness, numbness, and progressive bilateral hearing loss. He had first noticed problems with running in his early teens and at the age of 13 had two operations to correct bilateral pes cavus. His walking tolerance gradually deteriorated to half a mile unaided. At the age of 24, he had three operations to correct thoracic scoliosis and subsequently noticed progressive weakness of his hands. Since the age of 26 he had been aware of diminished sensation in his feet and progressive bilateral hearing loss. Medical history was unremarkable and he had not been exposed to any relevant drugs or toxins. There was no history of neurological problems among three siblings, his three children or the rest of his family. There was no parental consanguinity.
General medical examination disclosed bilateral pes cavus, palpable greater auricular nerves, and evidence of previous spinal surgery. Otoscopy was normal. Audiological examination showed bilateral sensorineural deafness (−40 dB at 6 kHz in both ears). Visual acuity, fundoscopy, and all other cranial nerves were normal. There was a typical essential tremor of both hands. In the limbs there was symmetric distal wasting, worse in the lower limbs, with corresponding weakness. Deep tendon reflexes were absent. Pinprick and vibration sensation were impaired in both feet.
Laboratory investigations showed no evidence of any underlying systemic disorder. Protein concentration in CSF was 1.55 g/l. Nerve conduction studies showed markedly diminished motor conduction velocities: right median nerve motor velocity was 16 m/s; right posterior tibial nerve motor velocity was 14m/s; sensory responses were unobtainable in the right sural and superficial peroneal nerves. Right sural nerve biopsy showed a severe demyelinating neuropathy with massive onion bulb formation. Genetic evaluation of a serum sample confirmed the presence of the PMP 22 duplication on chromosome 17. Brain stem auditory evoked responses (BAERs) were performed (table). Wave I latencies were significantly delayed compared with laboratory controls. Interwave I-V latencies were only marginally increased.
A recent paper on a series of 61 patients with the PMP 22 duplication reported no cases of deafness.1 However, deafness and asymptomatic abnormalities of BAERs has been reported in association with HMSN. In one kindred, 61 patients had a history of hearing loss in association with an autosomal dominant HMSN type 1.2 There were seven cases of sensorineural deafness among the 14 family members described by Cruse et al, 3 who had an autosomal dominant HMSN type 1. The four patients with symptomatic deafness described by Raglan et al 4 also conform to recognised criteria for a diagnosis of HMSN type 1 but more detailed clinical information on these patients is lacking. Perez et al 5 suggested, in a small community study, that the incidence of deafness in a mixed group of HMSN1 and HMSN 2 could be as high as 30%. Only the 77 year old female patient of Nicholsonet al 6 is definitely HMSN 1A, and it could be speculated whether at this age deafness is a coincidental symptom.
Nicholson et al 6 have recently renewed interest in auditory abnormalities in patients with HMSN 1A. Our patient conforms to the pattern they found, with isolated delayed wave I latencies suggesting a problem in the distal VIIIth nerve, in which PMP 22 expression is known to occur. This is the first case report to provide incontravertible evidence, with nerve biopsy and genetic analysis, of bilateral sensorineural deafness in a young patient with “a full house” phenotypically and genotypically for HMSN 1A.
Neurologists and otolaryngologists should be aware of this association, which may be commoner than previously thought.