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The spectrum of cytoplasmic body myopathy: Report of a congenital severe case
ORIGINAL ARTICLES
The Spectrum of Cytoplasmic Body Myopathy: Report of a Congenital Severe Case Yoshihiko Mizuno, MD, Yasuhide Nakamura, MD and Kazuhiko Komiya, MD
A 6-year-old girl presented with a myopathy - she was floppy since birth and developed progressive respiratory failure for which she required mechanical ventilation at age 6 months. Biopsy showed cytoplasmic bodies in about 15% of both type 1 and 2 muscle fibers. Of the 18 cases of cytoplasmic body myopathy (CBMj reported in the literature, 3 had symptoms at birth and in all of them the course was benign. Four clinical patterns emerged; aj congenital severe, b) congenital benign, c) juvenile severe and d) adult severe forms. Key words: Cytopfilsmic body myopathy, congenital myopathy, respiratory failure, congenital hypotonia, cfilssification. Mizuno Y, Nakamura Y, Komiya K. The spectrum of cytopfilsmic body myopathy: report of a congenital severe case. Brain Dev 1989; 11:20-5
Cytoplasmic body myopathy (CBM) is one of the congenital myopathies characterized by the presence of many cytoplasmic bodies (CBs) in the skeletal muscle. Clinically, CBM reveals rather heterogeneous characters as to heredity, age of onset, clinical symptoms and prognosis. Eighteen cases have been reported in the literature [1- 8] since the first case reported by Nakashima et al [1]. Among these, only three cases showed an infantile onset, although the clinical courses were far milder than in the present case. The onset in the cases with respiratory failure was from childhood to midlife. We report here a case of CBM who had a congenital onset and very severe clinical symptoms with respiratory failure in early life. Among the 18 cases 4 clinical patterns emerged.
CASE REPORT The patient is a 6-year-old Japanese girl. The family history was unremarkable and there was no consanguinity. The delivery was normal and her birth weight was 3,378 g. Respiratory distress was present due to a massive aspira-
From the Department of Pediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo (YM, KK); Maternal and Child Health Section, Beureau of Public Health, Tokyo Metropolitan Government, Tokyo (YN). Received for publication: June 15, 1988. Accepted for publication: August 31, 1988. Correspondence address: Dr. Yoshihiko Mizuno, Department of Pediatrics, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo 183, Japan.
tion syndrome. Her crying and sucking were also weak. She was floppy since birth and could not move her extremities against gravity. The respiratory disturbance gradually progressed and she was admitted to our hospital at the age of 3 months for precise examination. Status on admission revealed a slender baby with a body weight of 4 kg. Her body length was 61.5 cm. Her face was rather long and thin (Fig 1) and the high arched palate was seen. A funnel chest was observed (Fig 1) and respiration was of the retractive type. Hepatosplenomegaly was not seen. She was floppy and diffuse muscle atrophy was present. She had generalized weakness including facial and respiratory muscles. She could not lift her extremities and the only muscle activity observed was in the fingers and toes. Deep tendon reflexes were absent and there were no pathological reflexes. There was no fasciculations in the tongue and no tremor was seen in the fingers. Sensation was normal and she was mentally alert. Laboratory examinations were normal as to complete blood counts, urinalysis, thyroid functions, immunoglobulins, blood lactate and pyruvate, carnitine, and virus CFs for TORCH, ECHO, Coxsackie, Influenza, Para-influenza and Mycoplasma. The serum chemistry results were GOT 61 IV (normal 5-40), GPT 70 IV (normal 0-40), lDH 528 IV (normal 50-400), CK 178 IV (normal < 100) and aldolase 3.5 mgjdl (normal 0.5-3.1). Creatinine was 0.3 mgjdl. Otherwise, there were no abnormalities as to serum chemistry. Blood gas analysis revealed pH 7.33, PC02 47.2 mmHg, P0 2 58.5 mmHg, HC0 3- 24.3 MM/L and BE -1.7. There was no cardiomegaly, and electrocardiography was normal. CT scan and EEG were also normal. Motor and sensory nerve conduction velOcities were
within normal limits. Electromyography showed low amplitude motor units with some fibrillation discharges in the brachioradialis and rectus femoris muscles at rest. A muscle biopsy taken from the left quadriceps femoris muscle at the age of 4 months showed proliferation of peri· and endomysial connective tissues, and variation in the size of both type 1 and 2 fibers (Fig 2). The mean fiber diameters of types 1 and 2A were almost the same, and type 2B deficiency was observed (Fig 3). There was no inflammatory cell infJ.1tration. By modified Gomori· trichrome stain, single or multiple cytoplasmic bodies were observed in about 15% of both type 1 and 2 fibers (Fig 4). The electronmicroscopic picture of one of these inclusion bodies was typical of a cytoplasmic body (Fig 5). Nemaline rods, central core or myotubes were not observed. There was no accumulation of glycogen, lipids or mitochondria.
Fig 1 A photo of the patient at the age of 6 months. Marked hypotonia and a funnel chest can be seen.
Clinical course She could not attain any progress in her motor ability and she has been kept bed-ridden. The respiratory muscle weakness progressed gradually. The patient has been receiving mechanical respiratory assistance since the age of 6 months because of respiratory failure when the arterial blood PC0 2 level raised up to 90 mmHg. A course of steroid therapy was ineffective. Sudden unexplained cardiac arrest of short periods was occurred at the age of 1 which was treated with intra-cardiac injection of noradrenaline. She was tracheotomized at the age of 3 instead of the intratracheal intubation.
DISCUSSION Cytoplasmic body myopathy (CBM) is one of the congenital myopathies which is diagnosed on the basis of the presence of cytoplasmic bodies (CBs) in the muscle biopsy, and the exclusion of other conditions known to be sometimes associated with cytoplasmic bodies [9, 10]. The present case had a congenital onset of hypotonia, muscle atrophy and weakness, which included facial and respiratory muscles. The exsistence of the long thin face and the high arched palate suggest that this case shares the common clinical features of a congenital myopathy. The presence of CBs in the biopsied quadriceps muscle confirmed the diagnosis of CBM. The pathogenesis of CBM or CB has not yet been clarified, and CB itself has been reported to occur in various myopathies such as muscular dystrophies, myotonic dystrophy, inflammatory myopathies, and periodic
Fig 2 Left quadriceps femoris muscle. Modified Gomori-trichrome stain, x 260.
Mizuno et al: Cytoplasmic body myopathy 21
paralysis [10]. Recently, Chou and Mizuno [11] reported on the pathogenesis of experimentally induced spheroid cytoplasmic bodies (SCBs) in a rat plantaris muscle. These inclusions were produced under local tetanus conditions, for which the plantaris muscle was subjected to sustained
No. of fibers
. - . Type 1 (Mean:13/l)
100
( 46% H
0-0 Type 2A (Mean: 15 /l)
75
50
25
Diameter
o
10
20
30
40
50 /l
Fig 3 Histogram of the fiber diameter of the left quadriceps femolis muscle. Numbers in the parenthesis (*) mean the distribu·
contraction, which produced immobilization and shortening of the muscle fibers. These SCBs resemble the spheroid bodies demonstrated in the case of spheroid body myopathy [12]. These spheroid bodies were stained positively for desmin and actin immunohistochemically, desmin being stained in the central portion and actin in the peripheral portion of a spheroid body. Positive staining of desmin for cytoplasmic body was shown on a case of a life long congenital myopathy [13]. It is in good accordance with our results. Besides these spheroid bodylike inclusions some cytoplamic bodies were also observed in our experiments. We suggest that the spheroid body and the cytoplasmic body may not be different inclusions fundamentally, and that the differences may be attributed to the evolution of the inclusions under the influence of differences in the environments in which muscle fibers are situated. In that sense, the presence of CB would not be the cause of CBM but the result of some other genetically determined mechanisms which might cause immobilization of the muscle fibers. Nevertheless, we consider CBM as a definite disease entity at this point, just as in the case of nemaline myopathy. Although nemaline myopathy is accepted widely as a disease entity, the pathogenesis of a nemaline rod has not yet been clarified and, moreover, it has been seen in various myopathies and in experimental conditions such as tenotomy. Clinically, nemaline myopathy also shows wide variations in its onset and clinical symptoms as described later. The situations are the same in the case of CBM and the existence of hereditary cases in CBM supports the idea that CBM could stand as a distinct
tion of each fiber types.
Fig 4 Left quadriceps femoris
muscle. Many cytoplasmic bodies can be seen in muscle fibers in the center (arrowhead). Many other fibers contain single or multiple cytoplasmic bodies. Modified Comori-trichrome stain. x520.
22 Brain & Development, Vol 11, No 1, 1989
Fig 5 Electronmicroscopic picture of a cytoplasmic body. Bar = 1/1.
Clnical status 11(N)
2(F)
4(F)
Di ed-
Bed-
r i dden-
~hee
1-
cha i r-
10
20
30
40
50
60
70 Age(Y)
Fig 6 ainical courses of the reported cases of cytoplasmic body myopathy. Authors; 1: Namshima et al [IJ, 2: Kinoshita et al [2J, 3: Qark et al [3J, 4: Jerusalem et al [4J, 5, 6: Edstrom et al [5J, 7: Goebel et al [6J, 8, 9: Wolburg et al [7J, 10, 11, 12: Patel et al [8]. * the present case, M: male, F: female.
clinical entity. Since the first case of CBM reported by Nakashima et al [1], eighteen cases have been reported in the literature, as shown in Table l, 13 of which were reviewed by Patel et al [8] . However, no severe congenital case as the present one has been documented. According to the reports, it is apparent that CBM shows much heterogeneity as to its clinical features. The existence of the present case extended the concept of the heterogeneity of CBM further, and reveals the wide clinical spectrum of this disorder. Because the prognosis of CBM are variable, leading to death within a short period of time in some cases, we consider the clinical classification will be useful in anticipating the prognosis and in providing appropriate treatments for them from the beginning of the disease. Figure 6 illustrates the various clinical courses of the reported cases of CBM and 4 clinical patterns emerge. The onset may be at birth or very early life and these patients may present with hypotonia, delayed motor development, slow progressive course and they remain ambulant for a long period (cases 7, 8,9, 12) (the congenital benign form). On the other hand they may be floppy at birth and have early respiratory distress necessitating assisted respiration in infancy as in the present case (the congenital severe form). The condition may become apparent in childhood. The course then is rapidly progressive and respiratory failure occurs within a few years (cases 2, 4, 10, 11) (the juvenile severe form). When the onset occurs in adult life, the clinical course is rapidly progressive and the patients are confmed to the wheel-
Mizuno et al: Cytoplasmic body myopathy 23
Table 1 Reported cases of cytoplasmic body myopathy Authors
Year
Nakashima et al [1) Kinoshita et al (2) Clark et al (3) Jerusalem et al [4] Edstrom et al [5] Goebel et al [6] Wolburg et al [7] Patelet al [8] Kobayashi et al [14] Present case
1970 1975 1978 1979 1980 1981 1982 1983 1986
No of patient
Sex
1 2 1 2 1 2 3 5 1
M F M,F F M,F F M,F F,M,F M,M,M,F,F F
Heredity
+(AD) +(AD) -(AR?) +(AR?) +(AR)
Age of onset (years)
53 16 Late life Childhood Mid life Congenital Congenital 13, 5, congenital 31-50 Congenital
M: male, F: female, AD: autosomal dominant, AR: au tosomal recessive.
chair within 10-15 years (cases 1,3,5,6). The 2 adults reported by Kobayashi et al [14] also showed rapid deterioration (the adult severe form). As for heredity, three cases in the congenital benign form showed heredity, one being autosomal dominant (case 12) and the other being sibling cases (cases 8, 9). Two sibling cases (case 10, ll)in the juvenile severe form are the daughters of the case 12 who belongs to the congenital benign form. In general, children tend to become affected more severely than their parents, with an earlier onset in the dominantly inherited diseases. This may be applicable to this familial cases (cases 10, 11, 12). Finally, two cases in the adult severe form (cases 3, 5) showed autosomal dominant inheritance. Although various modes of inheritance are seen, each form could not be related to a special type of heredity as in the case of centronuc1ear myopathy as described later. This wide spectrum of clinical features is common to congenital myopathies. For example, in nemaline myopathy, besides the infantile non-progressive form, there is also a congenital severe form which shows very similar clinical features to those of the present case [15, 16]. Moreover, adult cases with late-onset progressive myopathy with nemaline rods have been reported [17]. Centronuc1ear myopathy (myotubular myopathy) is also divided into some subgroups according to the clinical symptoms. They are the severe X-linked form [18], early infantile autosomal recessive form [19] and late onset autosomal dominant form [20]. This wide clinical spectrum is also shared by cytoplasmic body myopathy. Collection of more cases of CBM will confirm the idea of classification both from the clinical and the genetic point of views.
REFERENCES 1. Nakashima N, Thamura Z, Okamoto S, Goto H. Inclusion
24 Brain & Development, Vol 11, No 1,1989
2. 3.
4.
5.
6.
7.
8. 9.
10.
11. 12. 13.
bodies in human neuromuscular disorders. Arch Neurol 1970;22:270-8. Kinoshita M, Satoyoshi E, Suzuki Y: Atypical myopathy with myofibrillar aggregates. Arch Neurol1975 ;32:417-9. Clark JR, d'Agostino AN, Wilson J, Brooks RR, Cole GC. Autosomal dominant myofiber inclusion body myopathy. Oinical, histologica~ histochemical and ultrastructural characteristics. Neurology (Minneap) 1978; 28: 399 (abstr). Jerusalem F, Ludin H, Bischoff A, Hartmann G. Cytoplasmic body neuromyopathy presenting as respiratory failure and weight loss. J Neurol Sci 1979;41:1-9. Edstrom L, Thronell LE, Eriksson A. A new type of distal myopathy with characteristic sarcoplasmic bodies and intermediate (skeletin) filaments. J Neurol Sci 1980;47: 171-90. Goebel HH, Schloon H, Lenard HG. Congenital myopathy with cytoplasmic bodies. Neuropediatrics 1981; 12:166-80. Wolburg H, Scholote W, Langohr HD, Peiffer J, Reiher KH, Heckl RW. Slowly progressive congenital myopathy with cytoplasmic bodies. Report of 2 cases and a review of the literature. Gin Neuropathol 1982; 1: 55-66. Patel H, Berry K, MacLeod P, Dunn HG. Cytoplasmic body myopathy. Report on a family and review of the literature. J Ne uro I Sci 1983;60:281-92. Engel WK. The essentiality of histo- and cytochemical studies of skeletal muscle in the investigation of neuromuscular disease. Neurology (Minneap) 1962; 12:778-94. MacDonald RD, Engel AG. The cytoplasmic body: another structural anomaly of the Z-disc. Acta Neuropathol (Berl) 1969;14:99-107. Chou SM, Mizuno Y. Induction of spheroid cytoplasmic bodies in a rat muscle by local tetanus. Muscle Nerve 1986; 9:455-64. Goebel HH, Muller J, Gillen HG, Merritt AD. Autosomal dominant "spheroid body myopathy." Muscle Nerve 1978; 1:14-26. Osborn M, Goebel MH. The cytoplasmic bodies in a congenital myopathy can be stained with antibodies to desmin, the muscle-specific intermediate filament protein. Acta
Neuropathol (Berl) 1983;62:149·52. 14. Kobayashi K, Mizuno Y, Suzuki H, Takase S. Oinicopathological study on familial cases of cytoplasmic body myopathy (in Japanese). Rinsho Shinkeigaku (Tokyo) 1986;26: 142 (abstr). 15. Kolin IS. Nemaline myopathy. A fatal case. Arner J Dis
Child 1967; 114 :95. 16. Shafiq SA, Dubowitz V, Peterson H de C, Milhorat AT. Nemaline myopathy: report of a fatal case with histochemical and electromicroscopic studies. Brain 1967;90:817-28. 17. Hefferman LP, Rewcastle NB, Humphrey JG. The spectrum of rod myopathies. Arch Neural 1968; 18: 529-42. 18. Van Wijngaarden GK, Fleury P, Bethlem J, Meijer AEFH. cal and electronmicroscopic studies. Brain 1967; 90: 817 -28.
1969; 19:901-8. 19. Spiro AJ, Shy GM, Gonatas NK. Myotubular myopathypersistence of fetal muscle in an adolescent boy. Arch Neurol 1966; 14: 1-14. 20. McLeod JG, Baker W de C, Lethlean AK, Chorey CD. Centronuc1ear myopathy with autosomal dominant inheritance. J Neural Sci 1972; 15 :375-87.
Mizuno et al: Cytoplasmic body myopathy
25
The Spectrum of Cytoplasmic Body Myopathy: Report of a Congenital Severe Case Yoshihiko Mizuno, MD, Yasuhide Nakamura, MD and Kazuhiko Komiya, MD
A 6-year-old girl presented with a myopathy - she was floppy since birth and developed progressive respiratory failure for which she required mechanical ventilation at age 6 months. Biopsy showed cytoplasmic bodies in about 15% of both type 1 and 2 muscle fibers. Of the 18 cases of cytoplasmic body myopathy (CBMj reported in the literature, 3 had symptoms at birth and in all of them the course was benign. Four clinical patterns emerged; aj congenital severe, b) congenital benign, c) juvenile severe and d) adult severe forms. Key words: Cytopfilsmic body myopathy, congenital myopathy, respiratory failure, congenital hypotonia, cfilssification. Mizuno Y, Nakamura Y, Komiya K. The spectrum of cytopfilsmic body myopathy: report of a congenital severe case. Brain Dev 1989; 11:20-5
Cytoplasmic body myopathy (CBM) is one of the congenital myopathies characterized by the presence of many cytoplasmic bodies (CBs) in the skeletal muscle. Clinically, CBM reveals rather heterogeneous characters as to heredity, age of onset, clinical symptoms and prognosis. Eighteen cases have been reported in the literature [1- 8] since the first case reported by Nakashima et al [1]. Among these, only three cases showed an infantile onset, although the clinical courses were far milder than in the present case. The onset in the cases with respiratory failure was from childhood to midlife. We report here a case of CBM who had a congenital onset and very severe clinical symptoms with respiratory failure in early life. Among the 18 cases 4 clinical patterns emerged.
CASE REPORT The patient is a 6-year-old Japanese girl. The family history was unremarkable and there was no consanguinity. The delivery was normal and her birth weight was 3,378 g. Respiratory distress was present due to a massive aspira-
From the Department of Pediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo (YM, KK); Maternal and Child Health Section, Beureau of Public Health, Tokyo Metropolitan Government, Tokyo (YN). Received for publication: June 15, 1988. Accepted for publication: August 31, 1988. Correspondence address: Dr. Yoshihiko Mizuno, Department of Pediatrics, Tokyo Metropolitan Neurological Hospital, 2-6-1 Musashidai, Fuchu-shi, Tokyo 183, Japan.
tion syndrome. Her crying and sucking were also weak. She was floppy since birth and could not move her extremities against gravity. The respiratory disturbance gradually progressed and she was admitted to our hospital at the age of 3 months for precise examination. Status on admission revealed a slender baby with a body weight of 4 kg. Her body length was 61.5 cm. Her face was rather long and thin (Fig 1) and the high arched palate was seen. A funnel chest was observed (Fig 1) and respiration was of the retractive type. Hepatosplenomegaly was not seen. She was floppy and diffuse muscle atrophy was present. She had generalized weakness including facial and respiratory muscles. She could not lift her extremities and the only muscle activity observed was in the fingers and toes. Deep tendon reflexes were absent and there were no pathological reflexes. There was no fasciculations in the tongue and no tremor was seen in the fingers. Sensation was normal and she was mentally alert. Laboratory examinations were normal as to complete blood counts, urinalysis, thyroid functions, immunoglobulins, blood lactate and pyruvate, carnitine, and virus CFs for TORCH, ECHO, Coxsackie, Influenza, Para-influenza and Mycoplasma. The serum chemistry results were GOT 61 IV (normal 5-40), GPT 70 IV (normal 0-40), lDH 528 IV (normal 50-400), CK 178 IV (normal < 100) and aldolase 3.5 mgjdl (normal 0.5-3.1). Creatinine was 0.3 mgjdl. Otherwise, there were no abnormalities as to serum chemistry. Blood gas analysis revealed pH 7.33, PC02 47.2 mmHg, P0 2 58.5 mmHg, HC0 3- 24.3 MM/L and BE -1.7. There was no cardiomegaly, and electrocardiography was normal. CT scan and EEG were also normal. Motor and sensory nerve conduction velOcities were
within normal limits. Electromyography showed low amplitude motor units with some fibrillation discharges in the brachioradialis and rectus femoris muscles at rest. A muscle biopsy taken from the left quadriceps femoris muscle at the age of 4 months showed proliferation of peri· and endomysial connective tissues, and variation in the size of both type 1 and 2 fibers (Fig 2). The mean fiber diameters of types 1 and 2A were almost the same, and type 2B deficiency was observed (Fig 3). There was no inflammatory cell infJ.1tration. By modified Gomori· trichrome stain, single or multiple cytoplasmic bodies were observed in about 15% of both type 1 and 2 fibers (Fig 4). The electronmicroscopic picture of one of these inclusion bodies was typical of a cytoplasmic body (Fig 5). Nemaline rods, central core or myotubes were not observed. There was no accumulation of glycogen, lipids or mitochondria.
Fig 1 A photo of the patient at the age of 6 months. Marked hypotonia and a funnel chest can be seen.
Clinical course She could not attain any progress in her motor ability and she has been kept bed-ridden. The respiratory muscle weakness progressed gradually. The patient has been receiving mechanical respiratory assistance since the age of 6 months because of respiratory failure when the arterial blood PC0 2 level raised up to 90 mmHg. A course of steroid therapy was ineffective. Sudden unexplained cardiac arrest of short periods was occurred at the age of 1 which was treated with intra-cardiac injection of noradrenaline. She was tracheotomized at the age of 3 instead of the intratracheal intubation.
DISCUSSION Cytoplasmic body myopathy (CBM) is one of the congenital myopathies which is diagnosed on the basis of the presence of cytoplasmic bodies (CBs) in the muscle biopsy, and the exclusion of other conditions known to be sometimes associated with cytoplasmic bodies [9, 10]. The present case had a congenital onset of hypotonia, muscle atrophy and weakness, which included facial and respiratory muscles. The exsistence of the long thin face and the high arched palate suggest that this case shares the common clinical features of a congenital myopathy. The presence of CBs in the biopsied quadriceps muscle confirmed the diagnosis of CBM. The pathogenesis of CBM or CB has not yet been clarified, and CB itself has been reported to occur in various myopathies such as muscular dystrophies, myotonic dystrophy, inflammatory myopathies, and periodic
Fig 2 Left quadriceps femoris muscle. Modified Gomori-trichrome stain, x 260.
Mizuno et al: Cytoplasmic body myopathy 21
paralysis [10]. Recently, Chou and Mizuno [11] reported on the pathogenesis of experimentally induced spheroid cytoplasmic bodies (SCBs) in a rat plantaris muscle. These inclusions were produced under local tetanus conditions, for which the plantaris muscle was subjected to sustained
No. of fibers
. - . Type 1 (Mean:13/l)
100
( 46% H
0-0 Type 2A (Mean: 15 /l)
75
50
25
Diameter
o
10
20
30
40
50 /l
Fig 3 Histogram of the fiber diameter of the left quadriceps femolis muscle. Numbers in the parenthesis (*) mean the distribu·
contraction, which produced immobilization and shortening of the muscle fibers. These SCBs resemble the spheroid bodies demonstrated in the case of spheroid body myopathy [12]. These spheroid bodies were stained positively for desmin and actin immunohistochemically, desmin being stained in the central portion and actin in the peripheral portion of a spheroid body. Positive staining of desmin for cytoplasmic body was shown on a case of a life long congenital myopathy [13]. It is in good accordance with our results. Besides these spheroid bodylike inclusions some cytoplamic bodies were also observed in our experiments. We suggest that the spheroid body and the cytoplasmic body may not be different inclusions fundamentally, and that the differences may be attributed to the evolution of the inclusions under the influence of differences in the environments in which muscle fibers are situated. In that sense, the presence of CB would not be the cause of CBM but the result of some other genetically determined mechanisms which might cause immobilization of the muscle fibers. Nevertheless, we consider CBM as a definite disease entity at this point, just as in the case of nemaline myopathy. Although nemaline myopathy is accepted widely as a disease entity, the pathogenesis of a nemaline rod has not yet been clarified and, moreover, it has been seen in various myopathies and in experimental conditions such as tenotomy. Clinically, nemaline myopathy also shows wide variations in its onset and clinical symptoms as described later. The situations are the same in the case of CBM and the existence of hereditary cases in CBM supports the idea that CBM could stand as a distinct
tion of each fiber types.
Fig 4 Left quadriceps femoris
muscle. Many cytoplasmic bodies can be seen in muscle fibers in the center (arrowhead). Many other fibers contain single or multiple cytoplasmic bodies. Modified Comori-trichrome stain. x520.
22 Brain & Development, Vol 11, No 1, 1989
Fig 5 Electronmicroscopic picture of a cytoplasmic body. Bar = 1/1.
Clnical status 11(N)
2(F)
4(F)
Di ed-
Bed-
r i dden-
~hee
1-
cha i r-
10
20
30
40
50
60
70 Age(Y)
Fig 6 ainical courses of the reported cases of cytoplasmic body myopathy. Authors; 1: Namshima et al [IJ, 2: Kinoshita et al [2J, 3: Qark et al [3J, 4: Jerusalem et al [4J, 5, 6: Edstrom et al [5J, 7: Goebel et al [6J, 8, 9: Wolburg et al [7J, 10, 11, 12: Patel et al [8]. * the present case, M: male, F: female.
clinical entity. Since the first case of CBM reported by Nakashima et al [1], eighteen cases have been reported in the literature, as shown in Table l, 13 of which were reviewed by Patel et al [8] . However, no severe congenital case as the present one has been documented. According to the reports, it is apparent that CBM shows much heterogeneity as to its clinical features. The existence of the present case extended the concept of the heterogeneity of CBM further, and reveals the wide clinical spectrum of this disorder. Because the prognosis of CBM are variable, leading to death within a short period of time in some cases, we consider the clinical classification will be useful in anticipating the prognosis and in providing appropriate treatments for them from the beginning of the disease. Figure 6 illustrates the various clinical courses of the reported cases of CBM and 4 clinical patterns emerge. The onset may be at birth or very early life and these patients may present with hypotonia, delayed motor development, slow progressive course and they remain ambulant for a long period (cases 7, 8,9, 12) (the congenital benign form). On the other hand they may be floppy at birth and have early respiratory distress necessitating assisted respiration in infancy as in the present case (the congenital severe form). The condition may become apparent in childhood. The course then is rapidly progressive and respiratory failure occurs within a few years (cases 2, 4, 10, 11) (the juvenile severe form). When the onset occurs in adult life, the clinical course is rapidly progressive and the patients are confmed to the wheel-
Mizuno et al: Cytoplasmic body myopathy 23
Table 1 Reported cases of cytoplasmic body myopathy Authors
Year
Nakashima et al [1) Kinoshita et al (2) Clark et al (3) Jerusalem et al [4] Edstrom et al [5] Goebel et al [6] Wolburg et al [7] Patelet al [8] Kobayashi et al [14] Present case
1970 1975 1978 1979 1980 1981 1982 1983 1986
No of patient
Sex
1 2 1 2 1 2 3 5 1
M F M,F F M,F F M,F F,M,F M,M,M,F,F F
Heredity
+(AD) +(AD) -(AR?) +(AR?) +(AR)
Age of onset (years)
53 16 Late life Childhood Mid life Congenital Congenital 13, 5, congenital 31-50 Congenital
M: male, F: female, AD: autosomal dominant, AR: au tosomal recessive.
chair within 10-15 years (cases 1,3,5,6). The 2 adults reported by Kobayashi et al [14] also showed rapid deterioration (the adult severe form). As for heredity, three cases in the congenital benign form showed heredity, one being autosomal dominant (case 12) and the other being sibling cases (cases 8, 9). Two sibling cases (case 10, ll)in the juvenile severe form are the daughters of the case 12 who belongs to the congenital benign form. In general, children tend to become affected more severely than their parents, with an earlier onset in the dominantly inherited diseases. This may be applicable to this familial cases (cases 10, 11, 12). Finally, two cases in the adult severe form (cases 3, 5) showed autosomal dominant inheritance. Although various modes of inheritance are seen, each form could not be related to a special type of heredity as in the case of centronuc1ear myopathy as described later. This wide spectrum of clinical features is common to congenital myopathies. For example, in nemaline myopathy, besides the infantile non-progressive form, there is also a congenital severe form which shows very similar clinical features to those of the present case [15, 16]. Moreover, adult cases with late-onset progressive myopathy with nemaline rods have been reported [17]. Centronuc1ear myopathy (myotubular myopathy) is also divided into some subgroups according to the clinical symptoms. They are the severe X-linked form [18], early infantile autosomal recessive form [19] and late onset autosomal dominant form [20]. This wide clinical spectrum is also shared by cytoplasmic body myopathy. Collection of more cases of CBM will confirm the idea of classification both from the clinical and the genetic point of views.
REFERENCES 1. Nakashima N, Thamura Z, Okamoto S, Goto H. Inclusion
24 Brain & Development, Vol 11, No 1,1989
2. 3.
4.
5.
6.
7.
8. 9.
10.
11. 12. 13.
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