Hereditary Hypertrophic Neuropathy Combining Features of Tic Douloureux, Charcot- Marie-Tooth Disease, and Deafness

Hereditary hypertrophic neuropathy combining features of tic douloureux, Charcot- Marie-Tooth disease, and deafness

Hereditary hypertrophic sensorimotor polyneuropathy combining the features of Charcot- Marie-Tooth disease, trigeminal neuralgia, and Robert P. Cruse, D.O. deafness occurred through four generations of John P. Conomy, M.D. a family originating in Haywood County, North Asa J. Wilbourn, M.D. Carolina. Fourteen individuals had pes cavus, Maurice R. Hanson, M.D. distal muscle atrophy, depressed or absent muscle stretch reflexes, cutaneous sensory deficits, Department of Neurology and defective proprioception. Six family members had recurrent, lancinating, trigeminal pain, and seven were deaf. The family was brought under scrutiny when the propositus, a 60-year-old woman, was examined for treat- ment of tic douloureux. Neurologic informa- tion was ultimately obtained regarding 52 family members. No history of consanguinity could be ascertained within this kinship. The genealogy of the family we studied is presented in Figure 1. In addition to clinical neurologic examinations, electromyographic and nerve conduction studies were obtained on those individuals indicated in the genealogy diagram. Audiometric studies were obtained when there was clinical indication of defective hearing. Quantitative cutaneous sensory testing was obtained in the propositus.

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• CMT a TIC Deaf CMT He Examined MS f Died O Not Affected 0 D led before age onset (O Multiple normal d1 ond j si be. -1—i Two Marriages —Indicates number of slbs.

Fig. 1. Hereditary neuropathy with features of Charcot-Marie-Tooth disease, tic douloureux, and deafness.

Case reports defective appreciation of pain, tempera- ture, and light touch sensation confined Case 1. This 60-year-old woman, to the second division of the left fifth complaining of facial pain, was examined cranial nerve. Hearing was diminished in October 1975. Pes cavus was present bilaterally. She further displayed moder- from childhood and she admitted a slowly ate peroneal muscle atrophy and pes ca- progressive disturbance of gait through- vus. Muscle stretch reflexes were hypoac- out her life. She first experienced left tive in her arms and absent in her legs. maxillary division tic douloureux at age There was mild weakness of intrinsic 41. Recurrent and progressively severe muscles of the hands and feet and of the facial pain was treated unsuccessfully muscles of the anterior and posterior with numerous medications, peripheral tibial compartments bilaterally. These nerve blocks, and acupuncture. In 1962 findings were associated with a Polyneu- she underwent intracranial section of the ropathie cutaneous sensory loss in her maxillary division of the left fifth cranial limbs. Her peripheral nerves were not nerve. Surgical procedure produced an- enlarged to palpation. esthesia in her face in an appropriate dis- Cerebrospinal fluid protein was 116 tribution, but relief of pain was only tem- mg/dl and other spinal fluid studies were porary, and tic douloureux returned in a normal. An audiogram revealed severe few months. She became aware of hear- sensorineural deafness with poor speech ing loss at age 47, which was progressive discrimination. An audiogram per- up to the time that she was examined. formed in 1957 had showed only mild Examination disclosed atrophy of the left bilateral hearing loss. Electromyographic masseter and temporalis muscles and syn- and nerve conduction studies showed no kinetic movements of the left side of her sensory-evoked responses in her distal face. The left pupil was slightly larger limb nerves. Motor conduction studies of than the right, and there was diminution the peroneal, ulnar, and median nerves of the left corneal reflex in addition to showed severely slowed motor conduc-

Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. Fall 1977 Hereditary hypertrophic neuropathy 109 tion velocities ranging from 19 to-22 m/sec mazepine ranging from 800 to 1200 mg/ (normal 40-70 m/sec). Motor nerve re- day. sponses could not be obtained in the legs. Case 2 (1-2). The mother of the pro- Needle electromyography revealed se- positus was the first family member vere, chronic denervation atrophy with known to be affected by this illness. She minimal fibrillations in distal muscles. had a staggering gait in childhood which Quantitative cutaneous sensory testing progressed to incapacitation later in life. was performed according to the method She first experienced facial pain at age 51 of Conomy and Barnes (Fig. 2). These and died at age 79 of an unknown cause. studies showed distal-proximal detection Case 3 (1-3). This woman had unilat- gradients, threshold elevations and di- eral paroxysmal facial pain, deafness, minished cycling frequencies, all of which and staggering gait. were consistent with cutaneous polyneu- Case 4 (II-4). This man had the onset ropathy; involvement.1,2 of unilateral tic douloureux at age 35. He A left sural nerve and gastrocnemius had high-arched feet, progressive gait muscle biopsy was performed and the tis- disorder, loss of muscle stretch reflexes, sues were subjected to neuropathologic and sensory defects in his legs. He died at examination. Peripheral nerve tissue age 55 reportedly of cerebral infarction. showed severe myelin loss with relative Case 5 (II-5). This woman had the on- axonal preservation. Electron micro- set of left-sided tic douloureux at age 46. scopic studies confirmed Schwann's cell She had bilateral pes cavus and gait diffi- membrane hyperplasia, severe demyeli- culties. She died at age 66 of complica- nation, and abortive remyelination. The tions of intracranial surgery performed muscle biopsy specimen showed changes in an effort to relieve her facial pain. consistent with chronic denervation Case 6 (II-l). This 51-year-old woman which was confirmed by further histo- was known to have a club foot from birth. chemical study of the tissue. Her examination showed mild distal The patient's tic douloureux has been muscle wasting and diminished stretch effectively controlled with doses of carba- reflexes. Electromyographic studies

Fig. 2. Sensorimotor neuropathy— tic douloureux.

Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. 110 Cleveland Clinic Quarterly Vol. 44, No. 3 ' showed a mixed sensorimotor abnormal- studies were normal. She was believed to ity of the peripheral nerves in the limbs. have multiple sclerosis and had no evi- Case 7 (III-5). This 33-year-old man dence of familial disease. had a history of "weak ankles" while in military service. He had pes cavus, de- Discussion pressed muscle stretch reflexes, and elec- Hereditary hypertrophic neurop- tromyographic and nerve conduction athy, confirmed by histopathologic studies consistent with a disorder of the examination in the propositus of this peripheral nerves. report, is rarely seen in association Case 8 (111-12). This 33-year-old with cranial nerve involvement. The woman complained of gait difficulty and mild deafness. She had high-arched feet findings in the family we report are and depressed stretch reflexes. Electro- reminiscent of the combination of physiologic studies revealed a mixed sen- findings seen in Hellsing's syn- sorimotor polyneuropathy. drome,3-5 but because of the detec- Case 9 (III-7). This 47-year-old man tion and confirmation of hyper- first experienced left-sided tic doulou- trophic polyneuropathy, we believe reux at age 30. He complained of im- this family to be a unique, phenotypic paired coordination since childhood and variant of familial hereditary neuro- had progressive deafness beginning in his pathic disease. Deafness seems to set early 30s. Clinical and electrophysiologic these patients apart from those pa- examination confirmed impairment of tients originally reported by Hellsing the peripheral nerves of the type seen in the other family members. Audiometry and other investigators. The family confirmed a sensorineural hearing loss. we studied shows a familial illness Case 10 (III-8). This 43-year-old with sensorineural deafness, trigemi- woman was known to have bilateral pes nal neuralgia, pes cavus, and a distal cavus. She was not examined. sensorimotor polyneuropathy. Pes

Case 11 (IV-26). A 672-year-old boy cavus was frequently noticed in in- showed mild pes cavus deformity bilat- fancy, and the deafness occurred in erally. Audiometry disclosed bilateral later childhood or in adult life. Tic conductive hearing loss with no evidence douloureux, present in six family of sensorineural abnormality. Electro- members, was always of early adult physiologic studies disclosed a mixed sen- onset in contrast to idiopathic trigem- sorimotor polyneuropathy. inal neuralgia which is usually a dis- Case 12 (IV-18). This 23-year-old woman was reported to have bilateral pes ease of old age. As with idiopathic cavus and absent stretch reflexes. trigeminal neuralgia, we achieved Case 13 (IV-1). This 15-year-old boy beneficial therapeutic response with was reported to have high-arched feet. the administration of carbamazepine. Case 14 (IV-9). This 672-year-old boy Electrophysiologic studies showed a had high-arched feet, but at this point has generalized and mixed sensory and not undergone an entirely normal neuro- motor neuropathy of segmental de- logic examination. Electromyogram and myelinating type with physiologic in- nerve conduction studies have been nor- volvement of the seventh and eighth mal. cranial nerves. Pathologic examina- Case 15 (1V-2). This 23-year-old tion in one patient disclosed a demye- woman was found to have transient intra- linative neuropathy accompanied by nuclear ophthalmoplegia and optic neu- ritis. Spinal fluid gammaglobulin was ele- hypertrophy of Schwann's cell mem- vated at 21 mg/dl. Her electromyographic branes suggesting that the biochemi-

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cal basis of this disease resides in al- References tered Schwann's cell metabolism. The genealogic studies are suggestive 1. Conomy JP, Barnes KL: A technique for the quantitative assessment of cutaneous of a dominant autosomal inheritance sensory function in subjects with neuro- with variable penetrance. The ele- logic disease. Trans Am Neurol Assoc 99: vated cerebrospinal fluid protein 83-87, 1974. level in the patient we studied sug- 2. Conomy JP, Barnes KL: Quantitative as- gested that the hypertrophic poly- sessment of cutaneous sensory function in subjects with neurologic disease. J Neurol neuropathic disease in this family Sei 30: 221-235, 1976. had an abnormal laboratory finding 3. Hellsing G: Hereditärer Facialiskrampf. in common with that in other hyper- Acta Med Scand 73: 526-537, 1930. trophic neuropathies, including De- 4. Lundberg PO, Westerberg CE: A heredi- jerine-Sottas disease and Refsum's tary neurological disease with facial spasm. J Neurol Sei 8: 85-100, 1969. syndrome. 5. Kalyanaraman K, Smith BH, Schlagen- Acknowledgment hauff RE: Hereditary hypertrophic neuropathy with facial and trigeminal involve- We thank Dr. Marta Steinberg for her ment; report of a case and comments on its assistance and advice in the study of this possible identity with Hellsing syndrome. family. Arch Neurol 31: 15-17, 1974.

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