LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES Dominantly Inherited Hypertrophic Neuropathy S. K. MONGIA, Q. GHANEM, D. PRESTON, A. J. LEWIS, AND E. A. ATACK SUMMARY: Clinical, electrophysiolog­ shoulder girdle muscles was seen in 13 Charcot and Marie (1886) and ical, and histopathological studies of patients. Four patients gave a history of Tooth (1886) first described an some members of a family with domin­ trigeminal neuralgia. Motor nerve con­ hereditary neuropathy, now called antly inherited hypertrophic neuropathy duction velocities were markedly im­ after their names, Charcot-Marie- are presented. Twenty-five members paired in all the clinically affected mem­ Tooth disease (CMT disease). A were studied. Seventeen were abnormal bers. These studies were normal in the 8 similar disorder was described by on clinical examination. Their ages var­ unaffected members. Motor conduction ied from 2lA to 78 years. Age at onset in velocities of the proximal segment of the Dejerine and Sottas (1893). Some of 14 of the 17 varied between 2 Vi and 56 ulnar nerve were slower compared to the the other hereditary neuropathies years. Pes cavus and palpable nerve distal segment in almost all the affected are Refsum's disease (Refsum, 1946) thickening were present in more than members. There was no significant cor­ hereditary sensory radicular half of the affected individuals. All pa­ relation between the degree of clinical neuropathy (Denny-Brown, 1951), tients had areflexia. Fifteen of the 17 had disability and the extent of impairment in Roussy-Levy syndrome (Roussy distal motor weakness as well as mild to the motor nerve conduction velocities. and Levy, 1926), Roussy-Cornil type moderate sensory impairment. Motor Sural nerve biopsies were studied. These of late onset (Roussy and Cornil, weakness affecting the proximal hip and observations are discussed. 1919), neuropathy of Friedreich's ataxia (McLeod, 1971), amyloid neuropathy (Bradley, 1974a) neuropathies of Bassen-Kornzweig RESUME: Nous presentons les aspects la hanche et aux epaules. 4 patients av­ disease (Farquhar and Ways, 1966), cliniques, electrophysiologiques et his- aient deja souffert de nevralgie du tri- Tangier's disease (Kocen, Lloyd topathologiques des divers membres jumeau. La vitesse de conduction ner- and Lascelles, 1967), porphyria d'une famille avec neuropathie hyper- veuse dans les nerfs moteurs etait net- (Cavanagh and Mellick, 1965) and trophique a heredite dominante. Des 25 tement diminuee chez tous les sujets at­ membres de cette famille examines, 17 teints, alors qu'elle se situait dans les leukodystrophies (Bradley, 1974b). semblaient atteints. Les ages variaient limites normales chez les sujets juges Metabolic abnormalities have been de 2V2 a 78 ans. L'age de debut deter­ normaux cliniquement. La vitesse de recognized in some of these and it is mine chez 14 patients variait egale- conduction motrice du segment proximal possible that a metabolic defect ex­ ment de 2Vi a 56 ans. Un pes cavus du nerf cubital etait nettement plus lente ists in the others. Hypertrophy of et une hypertrophic palpable du nerf se que celle du segment distal, chez pres- the peripheral nerves, thought to be retrouvaient chez plus de la moitie des que tous les sujets atteints. Cependant il characteristic of Dejerine-Sottas individus atteints. Tous etaient n'existait aucune correlation entre le neuropathy (also called hypertrophic areflexiques. Des 17 patients, 15 degre d'atteinte clinique et celui du ralentissement de la conduction dans les interstitial neuropathy), is seen in presentaient une faiblesse motrice dis- many chronic neuropathies and sig­ tale ainsi quune atteinte sensitive nerfs moteurs. Des biopsies surales moderee. De plus 13 patients avaient furent egalement faites. nifies recurrent demyelination and aussi une faiblesse motrice proximate a remyelination of the nerves (Thomas and Lascelles, 1967; Pleasure and Towfighi, 1972). It is seen in Dejerine-Sottas neuropathy, CMT disease, Refsum's disease, amyloid neuropathy (Dyck and Lambert, 1968 a and b), diabetic neuropathy (Thomas and Lascelles, 1967), re­ lapsing neuropathy (Austin, 1958), multifocal enlargement of peripheral From the Division of Neurology, Faculty of nerves (Adams, Asbury and Michel- Medicine, University of Ottawa and The Ottawa son, 1965). The neuropathy of ac­ Civic Hospital. romegaly (Stewart, 1966), neurofib­ Presented at the Canadian Congress of Neurologi­ romatosis (Bielschowski, 1922; cal Sciences, London, Ontario, June 1975. Bailey and Herman, 1938), and am­ Reprint requests to: Dr. E. A. A tack. Ottawa putation neuromas (Krucke, 1949) Civic Hospital, 1053 Carling Avenue, Ottawa, On­ tario, K1Y4E9, Canada. are other examples. Dejerine-Sottas Vol. 5, No. 2 MAY 1978 - 239 Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.229, on 26 Sep 2021 at 17:37:40, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0317167100024604 THE CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES TABLE 1 clinical, electrophysiological and histopathological studies are re­ Age and Sex Distribution ported. METHOD OF STUDY Age Group No. Males Females This family has thirty-nine mem­ bers over four generations. Twenty- five of these members were ex­ Clin cally Clinically amined by one or more of us. Infor­ Normal Affected Normal Affected mation was obtained about other members, but the data is restricted < 10 years 3 1 2 to those who were examined. Of these 25 members, 17 were 11-20 years 10 2 5 2 1 found to be abnormal (Table 1). These patients were divided into 21-30 years 4 1 1 2 four groups, depending upon the 31-40 years 4 2 2 severity of their clinical deficits (Table 2). 41-50 years 3 1 1 Motor nerve conduction velocities of the distal (elbow to wrist) and y 50 years 1 1 proximal (axilla to elbow) segments of the ulnar nerve and the knee to ankle segment of the lateral popliteal TOTAL 25 5 9 3 8 nerve were studied by conventional methods (Lambert, 1956). These studies were performed in 13 of the 17 abnormal and 6 of the 8 normal individuals (Table 3). Their ages var­ Table 2 ied from 11 to 50 years. Motor nerve conduction velocities of 45 m/sec or Grading of Neurological Deficit over for the lateral popliteal nerve were considered normal. Nerve conduction velocities in the affected Grade Description fo. of Patients members were classified into grades I-III as shown in Table 4. A decrease of 10 m/sec of conduction velocity I Areflexia with no motor or 2 separated one grade from the other. sensory impairment The grading of nerve conduction velocities and the clinical deficits II Mild weakness (4/5) with 8 was designed arbitrarily. mild sensory impairment plus areflexia Sural nerve biopsy was available from patients Bl, B4, C10, Cll, III Moderate weakness (2-3/5) 5 C12, and C13 as shown in Figure 1. with moderate sensory impair­ Gastrocnemius muscle biopsies ment plus areflexia were available from patients Bl and CI3. All specimens were picked up IV Marked weakness (0-1/5) with 2 immediately and prepared for teas­ moderate sensory impairment ing (of nerves), frozen section, plus areflexia paraffin section and electronmicros- copy. Standard techniques used for nerve and muscle included qualita­ tive histochemistry and enzyme his­ neuropathy and CMT disease may cessively inherited hypertrophic tochemistry. be inherited as dominant, recessive neuropathies rather than by All patients were subjected to the or sex-linked traits (Bell, 1935; Au­ eponyms. following hematological and stin, 1956; Thomas and Lascelles, This communication deals with biochemical studies: total and diffe­ 1967; Dyck and Lambert, 1968a). It the prospective study of a family rential blood cell counts; hemoglo­ is suggested these disorders might be with dominantly inherited hyper­ bin; erythrocytic sedimentation rate; better classified as dominantly or re- trophic neuropathy (Fig. 1). Detailed serum levels of sodium, potassium, 240 - MAY 1978 Dominant Hypertrophic Neuropathy Downloaded from https://www.cambridge.org/core. IP address: 170.106.35.229, on 26 Sep 2021 at 17:37:40, subject to the Cambridge Core terms of use, available at https://www.cambridge.org/core/terms. https://doi.org/10.1017/S0317167100024604 LE JOURNAL CANAD1EN DES SCIENCES NEUROLOGIQUES AGE OF ONSET ,2 - -.4 *.__ o- -oo ooo ©- BOD 66 C-IO C-lt C-12 C-IJ C-14 -I- -r f r/A -I— I 5 10 15 20 25 56 ©0 AGE OF ONSET Clinically affected Not available for study 3 Patients asymptomatic yet clinically affected. Figure /—Family pedigree showing both female and male indi­ Figure 2—The dots indicate the number of cases as they started viduals that were normal, clinically affected, or not available their symptoms at a particular age in years. Three patients for study. were asymptomatic but clinically affected and are not included in this figure. chloride, calcium, phosphorus, al­ showed tremor, pupillary abnor­ feature of all the patients. Distal kaline phosphatase, SGOT SGPT, malities, nystagmus, cerebellar or weakness of the lower extremities fasting and post-prandial blood long tract signs. Pes cavus and palp­ was seen in 15 patients. Thirteen of sugar. Serum electrophoresis for able nerve thickening were found in these 15 had weakness of the distal proteins and lipoproteins and more than half of the patients. muscles of the upper extremities. serological tests for syphilis were Mild to marked motor and moder­ Thirteen of the 15 patients had performed. Blood levels of arsenic, ate sensory deficits were seen in 15 significant proximal weakness, lead, mercury, and phytanic acid of the 17 patients. The other two pa­ mostly in the lower limbs. The pro- were assessed and X-rays of spine tients had no weakness, although were taken in some of the patients. they were areflexic and showed ab­ normal nerve conduction velocities. 70- OBSERVATIONS Absent deep tendon reflexes was a Of the 17 abnormal members, 9 ^ 60- were males (Table 1).