Distal muscular dystrophy with autosomal recessive inheritance

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  • Two sisters presented with distal weakness and their muscle biopsy was dystrophic. This distal muscular dystrophy has an autosomal re- cessive inheritance and its features are somewhat different from the more common autosomal dominant distal muscular dystrophy and in- clude: a) onset in early adult life; b) involvement of distal leg muscles and especially peroneal muscles; c) marked early elevation of serum creatine kinase (CK); d) brief duration, small amplitude motor units and fibrillation on electromyography; and e) histologic features of a dystro- phic myopathy.

    MUSCLE & NERVE 7:478-481 1984



    Distal muscular dystrophies are common in Scan- dinavian countries,""." and rare elsewhere. Its fea- tures are: a) autosonial dominant inheritance; b) onset in late adult life (usually after 40); c) involve- ment of the muscles of the hands and the forearm extensors, whereas the leg muscles are spared or slightly involved; d) slow and nondisabling evolu- tion; e) moderate eleLation of serum creatine ki- nase (CK); f ) myopathic EMG; and g) histologic features of a dystrophic myopathy.

    We have recently observed two sisters with dis- tal muscular dystrophy, presumably with auto- soma1 recessive inheritance, since the parents and grandparents were normal.

    Since in the most recent classifications of mus- cular dy~trophies,~-~, '" ' distal muscular dystrophy with autosomal recessive inheritance is not quoted, we believe it useful to present and discuss briefly these cases.

    From the Neurological Institute Catholic University 001 68 Rome Italy

    Acknowledgments The authors thank Dr S P Ringel from Denver CO for valuable suggestions

    Address reprint requests to Dr Scoppetta at the Neurological Institute Catholic University 00168 Rome Italy

    Received for publication September 7 1983 revised manuscript ac- cepted for publication January 12 1984

    01 48 639X/0706/0478 $04 OOiO 1984 John Wilev & Sons Inc


    Case 1. A 16-year-old girl noted moderate diffi- culty in walking on her heels for 4 months. Apart from this she felt well and complained only of minimal difficulty skiing and playing tennis. A general physical examination was normal.

    Neurological examination revealed moderate wasting and weakness of the peroneal muscles. The calf muscles were strong but markedly hyper- trophic and firm (Fig. 1). All other muscles were normal including the small muscles of the foot, and no other ahnormalities were detected on neuro- logical examination.

    Serum creatine kinase (CK) was 18,000 to 26,000 IU (normal value (nv) < 230 IU), pyruvate kinase (PK) was 1,686 to 1,900 IU (nv < 50 IU), lactic dehydrogenase (LDH) was 494 to 826 IU (nv < 190 IU), serum glutamic oxaloacetic transami- nase (SGOT) was 254 to 285 IU (nv < 50 IU), and serum glutamic pyruvic transaminase (SGPT) was 295 to 378 IU (nv < 40 IU) (Table 1). Other labo- ratory tests were normal including an electrocar- diogram and x-ray films of the lumbar spine and chest.

    Electromyograms (EMG) of the left tibialis and first peroneus muscles revealed occasional fibrilla- tion at rest, a full interference pattern with moder- ate effort, and many short-duration polyphasic motor unit potentials. The mean duration value of the motor units (an average of 26 motor units) at

    478 Distal Muscular Dystrophy MUSCLE & NERVE JtiliAtig 1984

  • FIGURE 1. (A) Case 1. (B) Case 2. Wasting and weakness of peroneal muscles; broad-based stance and (Case 1) hyper- trophic calves.

    the left tibialis anterior muscle was 7.2 msec (nor- mal mean value: 10.2 msec; normal limits: 8.2 to 12.2 msec). No myotonia was shown in any muscle. Normal findings were recorded from the left del- toid, brachial biceps, and quadriceps muscles. Motor and sensory nerve conductions were normal in both arms and legs.

    Muscle biopsy of the right tibialis anterior mus- cle revealed marked variation in fiber size with fre- quent splitting, occasional degenerating fibers with secondary vacuolar degeneration, necrotic fibers with associated phagocytosis, numerous internal nuclei, and occasional basophilic granules (Fig. 2). Histograms showed that the type 1 fibers were normal in size (mean fiber diameter: 49 pm; range: 5 to 85) and distribution (48%). Type 2 fibers (52%) were atrophic with a mean diameter of' 38 pm (range: 5 to 85) and an atrophy factor of 344.*

    Case 2. This 15-year-old girl, the sister of patient 1, noted difficulty in standing without shoes for 8 months because of a tendency to "fall down on her back. "

    Neurological examination revealed mild lum- bar lordosis and wasting and weakness of the peroneal muscles (Fig. 1) more marked than her sister. The calves were not hypertrophic but were firm.

    Serum CK was 9,900 to 17,200 IU; PK was 1,000 to 1,250 IU; LDH was 1,050 to 1,280 IU; SGOT was 153 to 229 IU; and SGPT was 163 to 213 IU (Table 1). No other laboratory abnor- malities were noted.

    The EMG was normal in proxiInal muscles (left deltoid, brachial biceps, and quadriceps), whereas the right tibialis anterior and first peroneus mus- cles showed: mild fibrillation at rest; many brief, small and polyphasic motor units (at the left tibialis anterior muscle the mean duration value from 24 motor units was 7.6 msec; the normal mean value was 10.2 msec; and the normal limits were 8.2 to 12.2 msec); and a full interference pattern with moderate efforts. Myotonic discharges were absent

    Table 1. Serum enzyme levels.

    CK PK LDH SGOT SGPT (nv* < 230 IU) (nv < 50 IU) (nv < 190 IU) (nv < 50 IU) (nv < 40 IU)

    2 9 5 - 3 7 8 Patient 1 18,000-26,000 1,686-1,900 494-826 254-285 (age 16)

    (age 15) Healthy sister 130 n d t 226 nd nd (age 12) Father 238-306 nd 154 nd nd (age 55) Mother 72-112 nd 202-340 nd nd (age 42)

    Patient 2 9,900-1 7,200 1,000-1,250 1,050-1,280 153-229 163-213

    *nv = normal value. t n d = not determined

    Distal Muscular Dystrophy MUSCLE 8, NERVE JuliAug 1984 479

  • (51%)-mean diameter 35 pm (5 to 65) with an atrophy factor over 250.


    No consanguinity was noted in the parents who came from different areas of Italy.

    On careful neurological examination there was no evidence of weakness and calves were of normal size and texture.

    Serial CK determinations were normal in the mother and slightly elevated (238 to 306 IU) in the father. Lactic dehydrogenase was normal in the father and slightly elevated (202 to 340 IU) in the mother (Table 1).

    The 12-year-old sister of cases 1 and 2 appeared completely healthy with no evidence of muscle weakness. Serial CK determinations were normal but LDH was slightly elevated (226 IU) (Table 1).

    The grandparents were reported to be healthy, but we did not examine them.

    FIGURE 2. Tibialis anterior muscle biopsies. (A) Case 1, hematoxylin and eosin. (B) Case 1, hematoxylin and eosin. (C) Case 2, ATPase (pH 9.4). Variation in fiber size, internal nuclei, some degenerating fibers with phagocytosis, split fibers, cytoplasmic vacuoles, mild proliferation of connective tissue, and (ATPase) atrophy mainly of the type 2 fibers. Bar = 50 pm.

    everywhere. Motor and sensory nerve conductions were normal.

    Muscle biopsy of the left tibialis anterior muscle in this case revealed similar alterations as in the muscle biopsy of her sister, including atrophy of the type 2 fibers: type 1 fibers (49%)-average di- ameter 42 pm (range 25 to 65); type 2 fibers


    Our patients undoubtedly have distal niusculai- dystrophy. Distal muscular dystrophy probably has an autosomal recessive inheritance, since the par- ents and presumably the grandparents are healthy. Moreover, the features of the disease in these pa- tients differ from those of dominantly inherited distal muscular dystrophy in that its onset was in early adult life, first involved the leg muscles, and induced a marked elevation of serum CK.

    Because of both of these genetical and clinical problems, autosomal recessive distal muscular dys- trophy appears to have a definite nosographical role.

    Some patients with many features similar to our patients who in the past were reported as having autosomal recessive distal myopathy"N,10 probably had true distal muscular dystrophy with autosomal recessive inheritance. And the same form of- the disease probably affected some of the few cases with similar features reported as having sporadic distal my~pathy;' .~, ' In . fact, autosomal recessive inheritance may appear as sporadic when only one person is affected in a pedigree.

    On the basis of this limited experience, distal muscular dystrophy with autosomal recessive in- heritance could be featured as follows: a) onset in early adult life; b) involvement of distal leg muscles first; c) moderate to marked early elevation o f serum CK; d) EMG evidence of myopathic damage despite the presence of fibrillation; and e) a his- tologic picture of a dystrophic myopathy.

    480 Distal Muscular Dystrophy MUSCLE & NERVE JuliAug 1984


    1. Dahlgaard E: Myopathia distalis tarda hereditaria. Actu Psycliialr Neurol Scarid 35:440-447, 1960.

    2. Dubowitz V, Brooke MH: Muscle Biupsy: A Modern Approach. Philadelphia, WB Saunders, 1973.

    3. Edstrom L: Histochemical and histopathological changes in skeletal muscle in late-onset hereditary distal myopathy. J Neurol Sci 26:147-157, 1975.

    4. Gardner-Medwin D: Clinical features and classification of the muscular dystrophies. Br Med Bull 36:109-115, 1980.

    5. Kratz R, Brooke MH: Distal myopathy, in V