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Nonspecific congenital myopathy (minimal change myopathy): A case report
Fig 2 Inversion recovery: TR =2000 ms, TD =350 ms, TE =30 ms. Heterotopic gray matter in the central part of the right hemisphere is evident in axial and coronal scans and displays an identical signal intensity to that of the cortical gray matter. In the left hemisphere, differentiation of the basal ganglia is clear, but it is obscure in the right one.
medial portion which forms the caudate nucleus and 2) a ventrolateral portion which develops into the lentiform nucleus. This division involves an ever-increasing number of afferent and efferent axons that pass to and from the cortex of the hemispheres and also break through the nuclear mass of the corpus striatum. The fiber bundle so formed is known as the internal capsule. The lentiform nucleus later becomes divided into a lateral portion, the putamen, and a medial portion, the globus pallidus [4]. In our patient we could not clearly observe differentiation of the putamen, caudate nucleus or internal capsule in the right hemisphere. Therefore we speculated that our case probably received some damage in the second fetal
Nonspecific Congenital Myopathy (Minimal Change Myopathy): A Case Report Yuh Jyh Jong, MD, Keiko Shishikura, MD, Masayuki Aoyama, MD, Hisae Kitahara, MD, Hideki Horita, MD, Makiko Osawa, MD, Haruko Suzuki, MD, Yoshito Hirayama, MD, Ekuko Nakada, MD, Kayoko Saito, MD, N oriko Okada, MD and Yukio Fukuyama, MD
A 28-month-old male with generalized hypotonia and muscle weakness, a myopathic face, skeletal dysmorphism and delayed motor milestones from birth is reported. He gradually developed the ability of sitting and rolling over, but could not stand without support until 28 months.
month.
REFERENCES 1. Bairamian 0, Di Chiro G, Theodore WH, Holmes MD, Dorwart RH, Larson SM. MR imaging and positron emission tomography of cortical heterotopia. J Comput Assist Tomogr 1985;9: 1137-9. 2. Deeb ZL, Rothfus WE, Maroon JC. MR imaging of heterotopic gray matter. J Comput Assist Tomogr 1985; 9: 1140-1. 3. Larroche J-C. The development of the central nervous system during intrauterine life. In: Falkner F, ed. Human development. Philadelphia: Saunders, 1966:257-76. 4. Langman 1. Medical embryology. Baltimore: Williams & Wilkins, 1969: 321.
There was no intellectual impairment or seizures. Deep tendon reflexes were absent. The serum CK value, peripheral nerve conduction velocity and EMG were within normal limits. A muscle biopsy specimen showed mild variation in fiber size, and an increased number of type 2C fibers on histochemical examination, but no apparent abnormalities on electron microscopy. The baby was tentatively diagnosed as having minimal change myopathy or nonspecific congenital myopathy which is thought to be one of the congenital nonprogressive myopathies. Key words: Congenital myopathy, minimal change myopathy, muscle pathology. Jong YJ, Shishikura K, A oyama M, Kitahara H, Horita H, Osawa M, Suzuki H, Hirayama Y, Nakada E, Saito K, Okada N, Fukuyama Y. Nonspecific congenital myopathy (minimal change myopathy): A case report Brain Dev 1987;9:61-64
----------------------
Although there have been many clinical reports concerning hypotonic children with a favorable prognosis such as in the cases of "myatonia congenita" [1], "benign congenital myopathy" [2], and "benign congenital hypotonia" [3], the recongnition of new myopathies actually began with Shy's [4] recognition of central core disease in 1956. Subsequently further entities were steadily added, including nemaline myopathy, myotubular myopathy, minicore disease, and other various subcellular abnormalities involving different organelles. These diseases were called "congenital nonprogressive myopathies" (CNM). Undoubtedly many of the cases diagnosed in the past would have been classified differently had they undergone a full histochemical or ultrastructural investigation. Even with the full battery of histochemical and electron microscopic examinations of muscle specimens, one sometimes still meets a case with the clinical characteristics of CNM: congential hypotonia and muscle weakness with facial muscle involvement and delayed motor milestones, but with no apparent histological abnormality. Dubowitz [5] first proposed the term minimal change myopathy or nonspecific congenital myopathy (NSCM) for this group, and some reports appeared thereafter [6, 7]. We described a similar case in this report and discussed the muscle pathology and differential diagnosis. CASE REPORT A fifteen-month-old male infant was first referred to us because of general hypotonia and muscle weakness from birth. He was born at 39 weeks' gestation by means of elective caesarean section on account of a breech presentation (and a bicornate uterus) to a 30-year-old primigravida who felt decreased fetal movement in the last trimester. The Apgar scores were 4 and 7 at 1 and 5 minutes, respectively. His birth weight was 2,892 gm. Pneumonia was noticed at the age of 3 days with dyspnea, and marked sucking and swallowing difficulty, and so he was hospitalized with tube feeding for 3 months. Sub-
From the Department of Pediatrics, Tokyo Women's Medical College, Tokyo (YJJ, KS, MO, HS, YH, EN, KS, NO, YF); Omiya Municipal Center for the Physically, Mentally and Auditorily Handicapped, Saitama (MA, HK, HH); Department of Pediatrics, Kaohsiung Medical College, Kaohsiung, Taiwan, Republic of China (YJJ). Received for publication: October 2, 1986. Accepted for publication: November 10, 1986. Correspondence address: Keiko Shishikura, MD, Department of Pediatrics, Tokyo Women's Medical College, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.
62 Brain & Development, Vol 9, No 1,1987
Fig 1 A 28·month-old child with a slender stature, a myopathic face (a poor facial expression, and tent-shaped lips with an occasional open mouth), low set ears, pectus excavatum, and sitting with a rounded back. sequently he showed poor feeding, marked hypotonia and muscle weakness. He obtained head control at 9 months and spoke two meaningful words at 1 year; but he was unable to sit alone or turn over himself. Neither seizures nor intellectual impairment was noted. There was no consanguinity and no family history of neuromuscular diseases. Physical examination at that time showed his weight to be 9,350 gm (10-25 percentile), length 77.9 cm (2550 percentile), head circumference 47.7 cm (50-75 percentile) and chest circumference 45.8 cm (10-25 percentile). He had a myopathic face (a poor facial expression and a tent-shaped mouth with occasional salivation), an antimongoloid slant, low set ears (Fig 1), diastasis recti, retentio testis, and some dysmorphic skeletal signs: dolichocephaly with frontal bossing, a high arched palate, pectus excavatum, and flexion contractures of both thenar proximal interphalangeal joints. Marked general hypotonia and muscle weakness were present with a pithed frog-posture, the heel to ear sign, the scarf sign, double folding, loose shoulder, the inverted U sign on ventral suspension, and marked head lag on the traction response. Abnormal motility of joints was also noted, such as hyperabduction of the hip joints, hyperextensibility of the knee joints, and hyperflexion of the ankle joints. Extraocular muscles were not involved. All tendon reflexes were absent. There was no evidence of muscular atrophy or pseudohypertrophy; fasciculation or intention tremor; or ankle clonus or any pathological reflexes. Myotonia was absent in the patient and his parents. The results of cranial CT scanning, bone age, chromosome, and inborn error screening tests were within normal limits. Serum creatine kinase (CK) activity and the peri-
Fig 2 Serial frozen sections of the quadriceps femoris muscle. There is mild variation in fiber size but no evidence of dystrophic change or disorganized intermyo· \. fibrillar networks (1). In addition to type 1 (1),2A (A) . and 2B (B) fibers distributed in the normal mosaic pattern, small-caliber type 1 (asterisks) fibers are scat· tered throughout and type 2C (C) fibers are increased in number (b-d). a: NADH-TR, b: routine ATPase, c: I ATPase with preincubation at pH 4.6, d: the same as in I c at pH 4.3; Bar'" 25 J.Lm. j
~
~
B
A
'
-
MUSCLE FIBER TYPE
pheral nerve conduction velocity were normal. Electromyography (EMG) showed polyphasic potentials in the right anterior tibial muscle but non-diagnostic findings in the other muscles. A biopsy specimen was taken from the left quadriceps femoris muscle and serial frozen sections were stained by a battery of histochemical methods. There was mild variation in fiber size, especially of type 1 fibers, and an increased number of type 2C fibers (Fig 2b-d). On NADH-TR staining, the distinction of fiber types was found to be well preserved with no disorganized intermyofibrillar networks (Fig 2a). On ATPase staining, the type 1, 2A and 2B fibers were found to be distributed in the normal mosaic pattern in most of the fascicles, while the number of type 1 fibers was slightly increased in some fascicles in which type 2B fibers were deficient. The mean fiber diameter was compatible with that in agematched control muscles (Fig 3). There was no additional evidence of atrophic fibers, abnormal inclusions, degeneration, internal nuclei, proliferation of connective tissue or other pathological changes. No intracytoplasmic structural abnormalities were seen with various histochemical methods. The glycogen and lipid contents of muscle fibers, and phosphorylase and phosphofructokinase activities were normal. No apparent abnormality was seen on electron microscopic examination. His parents were clinically normal, and both volunteered for muscle biopsies, the results of which were normal. On subsequent follow-up, the patient showed the ability of sitting without support at 17 months, and rolling over at 19 months, but he could not stand without support until 28 months. DISCUSSION On comprehensive histochemical and electron microscopic
21.4
MEAN DIAMETER (11m) STANDARD DE VIA TION PERCENTAGE OF FIBERS (%)
2A
2B
2C
20.2
21.9
21.7
4.2
3.3
3.8
3.5
44.1
23.9
27.8
4.2
70 60
If)
II:
~40 ii: II.
o
II:
~ 20
::I
::l
Z
5
15
25
35
DIAMETER (11m)
Fig 3 Fiber type distribution and fiber diameter histogram.
studies on the muscle specimen from the present patient, specific structural changes for CNM such as central cores, minicores, nemaline bodies, central nuclei or other subcellular abnormalities could not be detected. Congenital myotonic dystrophy was excluded by the absence of grip myotonia in both the mother and this case, and from the normal muscle pathology of the mother [8]. As to congenital fiber type disproportion (CFTD), this case showed only mild variation in fiber size and did not satisfy the criteria for CFTD [9] . The cardinal features of Ehlers-Danlos syndrome are hyperextensibility of the skin, poor wound healing with thin scarring, and hyperextensibility of the joints [9], but the former two findings were not prominent in this case and completely
Jong et al: Minimal change myopathy 63
absent in his parents. Dubowitz [10] described a 20-month-old infant with hypotonia and motor delay from birth. The first biopsy showed that there was veriation in fiber size but no other abnormality; he was able to stand unaided at six years but could not walk due to persistent fixed flexion contractures at the hips and knees; the second biopsy obtained at the time of tendo achilles tenotomy showed typical dystrophic features. The present case had a normal serum CK value, no gross fixed flexion contractures except for of both thenar proximal interphalangeal joints, no symptom or sign of central nervous system involvement and no conventional dystrophic change detectable in the muscle biopsy specimen; but we still entertain the possibility of a very mild form of "congenital muscular dystrophy", as Dubowitz documented. The most outstanding histochemical findings in various CNM (nemaline myopathy, central core disease, myotubular myopathy and CFTD) were small calibered fibers and an abnormal fiber type distribution, including type 1 fiber predominance and hypoplastic type 1 fibers. Nonaka et al [6] postulated that an increased number of type 2C fibers and an abnormal fiber type distribution in NSCM might reflect delayed or incomplete muscle fiber maturation, probably due to a defective neural influence on the developing muscle. The present case also showed an increased number of type 2C fibers, type 1 fiber predominance and type 2B fiber deficiency in some fascicles. The present patient showed clinical characteristics of CNM including generalized muscle weakness and hypotonia with facial muscle involvement, delayed motor milestones, and a normal intelligence. From these clinical symptoms, we had expected to see a certain specific morphologic finding for CNM. However, there was no contributory finding to explain his muscle weakness or hypotonia. It is possible that repeat biopsy examina-
64 Brain & Development, Vol 9, No 1,1987
tions on other muscels or at different times may reveal specific findings for certain CNM, because there might be the same pathogenetic mechanism in NSCM and CNM [6]. Since muscle biopsy of multiple muscles in a small infant would not be wise, we are following him up with the tentative diagnosis of NSCM until a definite final diagnosis is obtained. ACKNOWLEDGMENTS The authors wish to express their cordial thanks to Dr. Ikuya Nonaka (National Institute of Neuroscience, National Center for Neurology and Psychiatry (NCNP), Tokyo, Japan) for his kind suggestions and advice in this work. We are also grateful to the Takeda Science Foundation for the fellowship granted to one of us (YJJ) while part of the work was in progress. REFERENCES 1. Oppenheim H. Ueber allgemeine und localisierte Atonie der Muskulatur (Myatonie) im fruhen Kindesalter. Monatsschr Psychiatr Neurol 1900;8: 232-3. 2. Turner JWA. The relationship between amyotonia congenita and congenital myopathy. Brain 1940;63: 163-77. 3. Walton IN. Amyotonia congenita: a follow-up study. Lancet 1956;1: 1023-8. 4. Shy GM, Magee KR. A new congenital non-progressive myopathy. Brain 1956;79:610-21. 5. Dubowitz V. Muscle disorders in childhood. London-Philadelphia-Toronto: W. B. Saunders, 1978: 105-7. 6. Nonaka I, Nakamura Y, Tojo M, et al. Congenital myopathy without specific features (minimal change myopathy). Neuropediatrics 1983,14:237-41. 7. Yuza F, Tatsuno M, Okuyama K, Nonaka I. A case of congenital myopathy with no specific morphologic features (in Japanese). No To Hattatsu (Tokyo) 1986;18:70-2. 8. Harper PS. Congenital myotonic dystrophy in Britain. I. Clinical aspects. Arch Dis Child 1975 ;50:505-13. 9. Brooke MH. Congenital fiber type disproportion. In: Kakulas BA, ed. Ginical studies in myology. Vol 2. Amsterdam: Excerpta Medica, 1973: 147-59. 10. Dubowitz V. The floppy infant. 2nd ed. Clinics in developmental medicine, no. 76. Spastics International Medical Publications. Oxford: Blackwell, 1980: 61-2;84-5.
medial portion which forms the caudate nucleus and 2) a ventrolateral portion which develops into the lentiform nucleus. This division involves an ever-increasing number of afferent and efferent axons that pass to and from the cortex of the hemispheres and also break through the nuclear mass of the corpus striatum. The fiber bundle so formed is known as the internal capsule. The lentiform nucleus later becomes divided into a lateral portion, the putamen, and a medial portion, the globus pallidus [4]. In our patient we could not clearly observe differentiation of the putamen, caudate nucleus or internal capsule in the right hemisphere. Therefore we speculated that our case probably received some damage in the second fetal
Nonspecific Congenital Myopathy (Minimal Change Myopathy): A Case Report Yuh Jyh Jong, MD, Keiko Shishikura, MD, Masayuki Aoyama, MD, Hisae Kitahara, MD, Hideki Horita, MD, Makiko Osawa, MD, Haruko Suzuki, MD, Yoshito Hirayama, MD, Ekuko Nakada, MD, Kayoko Saito, MD, N oriko Okada, MD and Yukio Fukuyama, MD
A 28-month-old male with generalized hypotonia and muscle weakness, a myopathic face, skeletal dysmorphism and delayed motor milestones from birth is reported. He gradually developed the ability of sitting and rolling over, but could not stand without support until 28 months.
month.
REFERENCES 1. Bairamian 0, Di Chiro G, Theodore WH, Holmes MD, Dorwart RH, Larson SM. MR imaging and positron emission tomography of cortical heterotopia. J Comput Assist Tomogr 1985;9: 1137-9. 2. Deeb ZL, Rothfus WE, Maroon JC. MR imaging of heterotopic gray matter. J Comput Assist Tomogr 1985; 9: 1140-1. 3. Larroche J-C. The development of the central nervous system during intrauterine life. In: Falkner F, ed. Human development. Philadelphia: Saunders, 1966:257-76. 4. Langman 1. Medical embryology. Baltimore: Williams & Wilkins, 1969: 321.
There was no intellectual impairment or seizures. Deep tendon reflexes were absent. The serum CK value, peripheral nerve conduction velocity and EMG were within normal limits. A muscle biopsy specimen showed mild variation in fiber size, and an increased number of type 2C fibers on histochemical examination, but no apparent abnormalities on electron microscopy. The baby was tentatively diagnosed as having minimal change myopathy or nonspecific congenital myopathy which is thought to be one of the congenital nonprogressive myopathies. Key words: Congenital myopathy, minimal change myopathy, muscle pathology. Jong YJ, Shishikura K, A oyama M, Kitahara H, Horita H, Osawa M, Suzuki H, Hirayama Y, Nakada E, Saito K, Okada N, Fukuyama Y. Nonspecific congenital myopathy (minimal change myopathy): A case report Brain Dev 1987;9:61-64
----------------------
Although there have been many clinical reports concerning hypotonic children with a favorable prognosis such as in the cases of "myatonia congenita" [1], "benign congenital myopathy" [2], and "benign congenital hypotonia" [3], the recongnition of new myopathies actually began with Shy's [4] recognition of central core disease in 1956. Subsequently further entities were steadily added, including nemaline myopathy, myotubular myopathy, minicore disease, and other various subcellular abnormalities involving different organelles. These diseases were called "congenital nonprogressive myopathies" (CNM). Undoubtedly many of the cases diagnosed in the past would have been classified differently had they undergone a full histochemical or ultrastructural investigation. Even with the full battery of histochemical and electron microscopic examinations of muscle specimens, one sometimes still meets a case with the clinical characteristics of CNM: congential hypotonia and muscle weakness with facial muscle involvement and delayed motor milestones, but with no apparent histological abnormality. Dubowitz [5] first proposed the term minimal change myopathy or nonspecific congenital myopathy (NSCM) for this group, and some reports appeared thereafter [6, 7]. We described a similar case in this report and discussed the muscle pathology and differential diagnosis. CASE REPORT A fifteen-month-old male infant was first referred to us because of general hypotonia and muscle weakness from birth. He was born at 39 weeks' gestation by means of elective caesarean section on account of a breech presentation (and a bicornate uterus) to a 30-year-old primigravida who felt decreased fetal movement in the last trimester. The Apgar scores were 4 and 7 at 1 and 5 minutes, respectively. His birth weight was 2,892 gm. Pneumonia was noticed at the age of 3 days with dyspnea, and marked sucking and swallowing difficulty, and so he was hospitalized with tube feeding for 3 months. Sub-
From the Department of Pediatrics, Tokyo Women's Medical College, Tokyo (YJJ, KS, MO, HS, YH, EN, KS, NO, YF); Omiya Municipal Center for the Physically, Mentally and Auditorily Handicapped, Saitama (MA, HK, HH); Department of Pediatrics, Kaohsiung Medical College, Kaohsiung, Taiwan, Republic of China (YJJ). Received for publication: October 2, 1986. Accepted for publication: November 10, 1986. Correspondence address: Keiko Shishikura, MD, Department of Pediatrics, Tokyo Women's Medical College, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.
62 Brain & Development, Vol 9, No 1,1987
Fig 1 A 28·month-old child with a slender stature, a myopathic face (a poor facial expression, and tent-shaped lips with an occasional open mouth), low set ears, pectus excavatum, and sitting with a rounded back. sequently he showed poor feeding, marked hypotonia and muscle weakness. He obtained head control at 9 months and spoke two meaningful words at 1 year; but he was unable to sit alone or turn over himself. Neither seizures nor intellectual impairment was noted. There was no consanguinity and no family history of neuromuscular diseases. Physical examination at that time showed his weight to be 9,350 gm (10-25 percentile), length 77.9 cm (2550 percentile), head circumference 47.7 cm (50-75 percentile) and chest circumference 45.8 cm (10-25 percentile). He had a myopathic face (a poor facial expression and a tent-shaped mouth with occasional salivation), an antimongoloid slant, low set ears (Fig 1), diastasis recti, retentio testis, and some dysmorphic skeletal signs: dolichocephaly with frontal bossing, a high arched palate, pectus excavatum, and flexion contractures of both thenar proximal interphalangeal joints. Marked general hypotonia and muscle weakness were present with a pithed frog-posture, the heel to ear sign, the scarf sign, double folding, loose shoulder, the inverted U sign on ventral suspension, and marked head lag on the traction response. Abnormal motility of joints was also noted, such as hyperabduction of the hip joints, hyperextensibility of the knee joints, and hyperflexion of the ankle joints. Extraocular muscles were not involved. All tendon reflexes were absent. There was no evidence of muscular atrophy or pseudohypertrophy; fasciculation or intention tremor; or ankle clonus or any pathological reflexes. Myotonia was absent in the patient and his parents. The results of cranial CT scanning, bone age, chromosome, and inborn error screening tests were within normal limits. Serum creatine kinase (CK) activity and the peri-
Fig 2 Serial frozen sections of the quadriceps femoris muscle. There is mild variation in fiber size but no evidence of dystrophic change or disorganized intermyo· \. fibrillar networks (1). In addition to type 1 (1),2A (A) . and 2B (B) fibers distributed in the normal mosaic pattern, small-caliber type 1 (asterisks) fibers are scat· tered throughout and type 2C (C) fibers are increased in number (b-d). a: NADH-TR, b: routine ATPase, c: I ATPase with preincubation at pH 4.6, d: the same as in I c at pH 4.3; Bar'" 25 J.Lm. j
~
~
B
A
'
-
MUSCLE FIBER TYPE
pheral nerve conduction velocity were normal. Electromyography (EMG) showed polyphasic potentials in the right anterior tibial muscle but non-diagnostic findings in the other muscles. A biopsy specimen was taken from the left quadriceps femoris muscle and serial frozen sections were stained by a battery of histochemical methods. There was mild variation in fiber size, especially of type 1 fibers, and an increased number of type 2C fibers (Fig 2b-d). On NADH-TR staining, the distinction of fiber types was found to be well preserved with no disorganized intermyofibrillar networks (Fig 2a). On ATPase staining, the type 1, 2A and 2B fibers were found to be distributed in the normal mosaic pattern in most of the fascicles, while the number of type 1 fibers was slightly increased in some fascicles in which type 2B fibers were deficient. The mean fiber diameter was compatible with that in agematched control muscles (Fig 3). There was no additional evidence of atrophic fibers, abnormal inclusions, degeneration, internal nuclei, proliferation of connective tissue or other pathological changes. No intracytoplasmic structural abnormalities were seen with various histochemical methods. The glycogen and lipid contents of muscle fibers, and phosphorylase and phosphofructokinase activities were normal. No apparent abnormality was seen on electron microscopic examination. His parents were clinically normal, and both volunteered for muscle biopsies, the results of which were normal. On subsequent follow-up, the patient showed the ability of sitting without support at 17 months, and rolling over at 19 months, but he could not stand without support until 28 months. DISCUSSION On comprehensive histochemical and electron microscopic
21.4
MEAN DIAMETER (11m) STANDARD DE VIA TION PERCENTAGE OF FIBERS (%)
2A
2B
2C
20.2
21.9
21.7
4.2
3.3
3.8
3.5
44.1
23.9
27.8
4.2
70 60
If)
II:
~40 ii: II.
o
II:
~ 20
::I
::l
Z
5
15
25
35
DIAMETER (11m)
Fig 3 Fiber type distribution and fiber diameter histogram.
studies on the muscle specimen from the present patient, specific structural changes for CNM such as central cores, minicores, nemaline bodies, central nuclei or other subcellular abnormalities could not be detected. Congenital myotonic dystrophy was excluded by the absence of grip myotonia in both the mother and this case, and from the normal muscle pathology of the mother [8]. As to congenital fiber type disproportion (CFTD), this case showed only mild variation in fiber size and did not satisfy the criteria for CFTD [9] . The cardinal features of Ehlers-Danlos syndrome are hyperextensibility of the skin, poor wound healing with thin scarring, and hyperextensibility of the joints [9], but the former two findings were not prominent in this case and completely
Jong et al: Minimal change myopathy 63
absent in his parents. Dubowitz [10] described a 20-month-old infant with hypotonia and motor delay from birth. The first biopsy showed that there was veriation in fiber size but no other abnormality; he was able to stand unaided at six years but could not walk due to persistent fixed flexion contractures at the hips and knees; the second biopsy obtained at the time of tendo achilles tenotomy showed typical dystrophic features. The present case had a normal serum CK value, no gross fixed flexion contractures except for of both thenar proximal interphalangeal joints, no symptom or sign of central nervous system involvement and no conventional dystrophic change detectable in the muscle biopsy specimen; but we still entertain the possibility of a very mild form of "congenital muscular dystrophy", as Dubowitz documented. The most outstanding histochemical findings in various CNM (nemaline myopathy, central core disease, myotubular myopathy and CFTD) were small calibered fibers and an abnormal fiber type distribution, including type 1 fiber predominance and hypoplastic type 1 fibers. Nonaka et al [6] postulated that an increased number of type 2C fibers and an abnormal fiber type distribution in NSCM might reflect delayed or incomplete muscle fiber maturation, probably due to a defective neural influence on the developing muscle. The present case also showed an increased number of type 2C fibers, type 1 fiber predominance and type 2B fiber deficiency in some fascicles. The present patient showed clinical characteristics of CNM including generalized muscle weakness and hypotonia with facial muscle involvement, delayed motor milestones, and a normal intelligence. From these clinical symptoms, we had expected to see a certain specific morphologic finding for CNM. However, there was no contributory finding to explain his muscle weakness or hypotonia. It is possible that repeat biopsy examina-
64 Brain & Development, Vol 9, No 1,1987
tions on other muscels or at different times may reveal specific findings for certain CNM, because there might be the same pathogenetic mechanism in NSCM and CNM [6]. Since muscle biopsy of multiple muscles in a small infant would not be wise, we are following him up with the tentative diagnosis of NSCM until a definite final diagnosis is obtained. ACKNOWLEDGMENTS The authors wish to express their cordial thanks to Dr. Ikuya Nonaka (National Institute of Neuroscience, National Center for Neurology and Psychiatry (NCNP), Tokyo, Japan) for his kind suggestions and advice in this work. We are also grateful to the Takeda Science Foundation for the fellowship granted to one of us (YJJ) while part of the work was in progress. REFERENCES 1. Oppenheim H. Ueber allgemeine und localisierte Atonie der Muskulatur (Myatonie) im fruhen Kindesalter. Monatsschr Psychiatr Neurol 1900;8: 232-3. 2. Turner JWA. The relationship between amyotonia congenita and congenital myopathy. Brain 1940;63: 163-77. 3. Walton IN. Amyotonia congenita: a follow-up study. Lancet 1956;1: 1023-8. 4. Shy GM, Magee KR. A new congenital non-progressive myopathy. Brain 1956;79:610-21. 5. Dubowitz V. Muscle disorders in childhood. London-Philadelphia-Toronto: W. B. Saunders, 1978: 105-7. 6. Nonaka I, Nakamura Y, Tojo M, et al. Congenital myopathy without specific features (minimal change myopathy). Neuropediatrics 1983,14:237-41. 7. Yuza F, Tatsuno M, Okuyama K, Nonaka I. A case of congenital myopathy with no specific morphologic features (in Japanese). No To Hattatsu (Tokyo) 1986;18:70-2. 8. Harper PS. Congenital myotonic dystrophy in Britain. I. Clinical aspects. Arch Dis Child 1975 ;50:505-13. 9. Brooke MH. Congenital fiber type disproportion. In: Kakulas BA, ed. Ginical studies in myology. Vol 2. Amsterdam: Excerpta Medica, 1973: 147-59. 10. Dubowitz V. The floppy infant. 2nd ed. Clinics in developmental medicine, no. 76. Spastics International Medical Publications. Oxford: Blackwell, 1980: 61-2;84-5.