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UNLABELLED: The aim of this work was to assess the hearing impairment in patients with hereditary motor and sensory neuropathy (HMSN). Elevation of pure tone thresholds in the presence of preserved inner ear function as suggested by cochlear microphonics (CM), absent or markedly abnormal brainstem auditory evoked potentials (BAEP), and elevation of speech perception out of proportion to the pure tone loss were found in the patients. From 28 members of a Gypsy family, we examined two siblings aged 31 and 30 years and their nephew aged 20 years, all suffering from HMSN that was associated with auditory neuropathy. All three affected members with difficulty of understanding speech had following investigations: pure tone and speech audiograms, BAEP, cochlear microphonics, and nerve conduction studies (NCV). RESULTS: the older two siblings had a flat 80 dB audiogram, whereas the younger one has flat 20 dB audiogram on the Lt. ear and 30 dB audiogram on the Rt. ear. All had no speech comprehension and no BAEP. Two patients had preserved cochlear microphonics on one ear. Peripheral nerves were electrically not elicitable, however, at the beginning of the disease nerve conduction was slow. CONCLUSION: in all three affected members with distinct clinical picture of HMSN their hearing impairment was proved to be due to severe auditory neuropathy in the presence of preserved inner ear function.

Objective To define auditory nerve and cochlear functions in two families with autosomal dominant axonal Charcot-Marie-Tooth (CMT). Methods Affected members in two families with different point mutations of NF - L gene were screened with auditory brainstem responses (ABRs). Those with abnormal ABRs were further investigated with clinical, neurophysiological and audiological procedures. The point mutations of NF - L gene involved were Glu397Lys in 8 affected members of the family with AN, and Pro22Ser in 9 affected members of the family without AN. Results ABRs and stapedial muscle reflexes were absent or abnormal in affected members of only one family consistent with auditory neuropathy (AN). In them, audiograms, otoacoustic emissions, and speech comprehension were normal. Absent or abnormal ABRs were consistent with slowing of conduction along auditory nerve and/or brainstem auditory pathway. Wave I when present was of normal latency. Conclusions Auditory nerve involvement in the presence of normal cochlear outer hair cell activity is asymptomatic in one of two families with CMT disorder with different point mutations of the NF - L gene. The nerve disorder is consistent with altered synchrony and slowed conduction. Significance The absence of "deafness" may reflect the ability of central mechanisms to compensate for the slowly developing auditory nerve abnormalities.

Hereditary motor and sensory neuropathy type Lom, initially identified in Roma (Gypsy) families from Bulgaria, has been mapped to 8q24. Further refined mapping of the region has been undertaken on DNA from patients diagnosed across Europe. The refined map consists of 25 microsatellite markers over approximately 3 cM. In this collaborative study we have identified a number of historical recombinations resulting from the spread of the hereditary motor and sensory neuropathy type Lom gene through Europe with the migration and isolation of Gypsy groups. Recombination mapping and the minimal region of homozygosity reduced the original 3 cM hereditary motor and sensory neuropathy type Lom region to a critical interval of about 200 kb. (C) 2000 Elsevier Science B.V.

Members of a Roma (Gypsy) family with hereditary motor and sensory peripheral neuropathy (HMSN) and concomitant auditory and vestibular cranial neuropathies were identified in Kocevje, Slovenia. The illness begins in childhood with a severe and progressive motor disability and the deafness is delayed until the second decade. There are no symptoms of vestibular dysfunction. The family structure is consistent with an autosomal recessive pattern of inheritance and the genetic locus for the disorder is linked to the same region of chromosome 8q24 as other Roma families with HMSN and deafness from Lom, Bulgaria (HMSN-Lom). The present study shows that the deafness is caused by a neuropathy of the auditory nerve with preserved measures of cochlear outer hair cell function (otoacoustic emissions and cochlear microphonics) but absent neural components of auditory brainstem potentials. The hearing loss affects speech comprehension out of proportion to the pure tone loss. Vestibular testing showed absence of caloric responses. Physiological and neuropathological studies of peripheral nerves were compatible with the nerve disorder contemporaneously affecting Schwann cells and axons resulting in both slowed nerve conduction and axonal loss. Genetic linkage studies suggest a refinement of the 8q24 critical region containing the HMSN-Lom locus that affects peripheral motor and sensory nerves as well as the cranial auditory and vestibular nerves.