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The rigid spine syndrome and Emery-Dreifuss muscular dystrophy
The rigid spine syndrome and Emery-Dreifuss muscular dystrophy I k u o G o t o * , Shinji I s h i m o t o * , T a k e s h i Y a m a d a * , H i d e o H a r a * * a n d Y o s h i g o r o K u r o i w a *
Introduction Summary Rigid spine syndrome has been described by many authors ill. It usually has a childhood onset and affects males. The syndrome presents with limitation of neck and back flexion, joint contractures in elbows and feet. There is hardly any progression of weakness and atrophy in the extremities. The nosological entity of the rigid spine syndrome and Emery-Dreifuss muscular dystrophy has been discussed 1113. The purpose of this paper is to describe the clinical features and findings in rigid spine syndrome and Emery-Dreifuss muscular dystrophy.
Case reports Case 16: A 25-year-old Japanese male was observed to run more slowly than his peers at age 3 years. At age 6 years, a limitation of neck and back flexion and weakness of extremities were evident. There was no obvious progression of symptoms. Examination at the age of 16 years showed a high arched palate, mild scoliosis, limitation of neck flexion and a mild degree of limitation of extension of both elbows and knees. There was no intellectual impairment. The sternocleidomastoid muscles were weak and atrophic. There were a mild degree of muscular
We present five patients, three of whom suffered from a rigid spine syndrome and two from Emery-Dreifuss muscular dystrophy. One patient with rigid spine syndrome showed a nonprogressive course, normal cardiac rhythm and mild myopathic changes in muscle histology, while in the other two patients there was a rapidly progressive course, sinus tachycardia without cardiac conduction defects and marked fiber necrosis in muscle histology. The two patients suffering from EmeryDreifuss muscular dystrophy showed a very mildly progressing course, myopathic changes in muscle histology, cardiac conduction defects and deviations in electrocardiograms. These findings show that rigid spine syndrome can be distinguished from Emery-Dreifuss muscular dystrophy. Key words: Rigid spine syndrome, EmeryDreifuss muscular dystrophy, ECG.
weakness and atrophy and hypoactive reflexes without pathological reflexes in all four extremities. Neither sensory impairment nor cerebellar signs were found. Routine laboratory studies were normal except for an elevated serum creatine kinase level. There was no ankylosis nor any destructive process of the
* Department of Neurology, Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka, * * National Chikugo Hospital, Chikugo City, Fukuoka, Japan. Address for correspondence and reprint requests: Ikuo Goto, Department of Neurology, Neurological Institute, Faculty of Medicine, Kyushu University 60, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan 812. Accepted 10. 7.86 Clin Neurol Neurosurg 1986. Vol. 88-4.
293
Table 1. Synopsis of clinical and laboratory data of three cases of rigid spine syndrome and two cases of Emery Dreifuss muscular dystrophy. Patient Age (years), sex Clinical progression Age of onset (years) Consanguinity (first cousins) Family history Endocrine functions Creatine kinase (normal; < 70, * < 28) Muscle histology Fiber size variation Increases of connective tissues Increases of internal nuclei Fiber necrosis Electrocardiogram
25, male no worsening
18, male died, age 18
15, male died, age 15
29, male
6 +
6
6 +
6 +
(grandparents)
(grandparents)
normal 262
normal
(grandparents)
50, male died, age 50 12
+ normal 338
normal 693
+
+++
+
+--++
+
+ +++
+
normal rhythm
+ , very mild; + mild; + + , moderate; + + +
sinus taehycardia
+++ ++--+++ +++ +++
sinus tachycardia
294
normal 20*
++
++
++ +
+
complete atrioventricular blocks
++ +
absence of P waves, junctional rhythm
severe.
spine. EMG showed motor unit potentials (MUP) of low amplitude and short duration and full interference patterns without spontaneous discharge at rest. Histological and histochemical studies of the right biceps muscle revealed mild to moderate fiber size variability in both type 1 and type 2 fibers and mild increases in endomysial and perimysial connective tissues, but no vacuolar degeneration, inflammatory cell infiltration, mitochondrial abnormalities or ragged-red fiber were evident (Table 1). Electron microscopic examination showed no remarkable abnormality. ECG showed norrn"alrhythm with right axis deviation (Fig. 1). After ten years follow-up, the patient evinced no demonstrable worsening of muscle strength or contracture. ECG still showed normal rhythm with right axis deviation. Case 27: An 18-year-old Japanese boy developed limitation of neck flexion and extension of the elbows at the age of 6 years. The patient noticed weakness of the lower extremities at the age of 10 years and weakness of the upper extremities a year later. His symptoms were slowly progressive. Examination at the age of 13 years showed a high arched palate, low hairline, limitation of neck flexion and a mild degree of limitation of extension of both the elbows and the knees.
294
slow
Intelligence was normal. The sternocleidomastoid muscles were weak and atrophic. There was a mild to moderate degree of muscular weakness and atrophy, predominantly in the proximal portion of the extremities. There were hypoactive reflexes without pathological reflexes. Neither sensory impairment nor cerebellar signs were noted. Routine laboratory examinations were normal except for an elevated creatine kinase level. There was no destructive process of the spine. EMG revealed MUP of low amplitude and short duration, mild fibrillation potentials and full interference patterns. Histological and histochemical studies of the right biceps muscle showed marked variation in fiber size, mild increases in endomysial and perimysial connective tissues, central nuclei, degenerative changes in both type 1 and type 2 fibers, sarcoplasmic mass, phagocytosis, vacuolar degeneration and mild perivascular cell infiltrations, but no mitochondrial abnormalities or ragged-red fiber were seen. Electron microscopic examination revealed membranous whorls, cytoplasmic bodies and abnormal filaments. ECG was normal at the age of 13 (Fig. 1). The patient suffered from sinus tachycardia without conduction defect until he died suddenly at the age of 18 (Fig. 1).
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Fig. 1. E C G shows normal r h y t h m in patient 1, n o r m a l r h y t h m at age 13 and sinus tachycardia at age 18 in patient 2, sinus tachycardia in patient 3, complete atrioventricular blocks in patient 4 (intraatrial E C G shows A waves), and junctional r h y t h m and absence of P waves in patient 5.
Case 314: A 15-year-old Japanese boy showed mild weakness of the four extremities at the age of 6. His symptoms were slowly progressive. Neurological examination at the age of 15 revealed a high arched palate, marked limitation of neck flexion, contractures of the elbows and knees, scoliosis and deformity of the thorax. Mentation was normal. Diffuse and marked muscular weakness and atrophy were observable in the upper extremities and a mild to moderate degree of weakness and atrophy was found in the lower extremities, predominantly the proximal portion of the extremities. The sternocleidomastoid muscles were weak and atrophic. Deep tendon reflexes were all absent. Routine laboratory studies were normal except
for an elevated serum creatine kinase activity. EMG revealed MUP of low amplitude and short duration with no spontaneous discharge at rest. Muscle histology of the right deltoid showed marked variation in fiber size, moderate increases in endomysial and perimysial connective tissues, central nuclei, fiber splitting, ring fiber, sarcoplasmic mass, ghost fibers and mild to moderate cell infiltrations, but no mitochondrial abnormalities or ragged-red fiber were seen (Table 1, Fig. 2). Electron microscopic examination revealed membranous whorls, a lot of cytoplasmic bodies and rod-like particles (Fig. 3). The patient had suffered from sinus tachycardia without conduction defects during three months of follow-up, until he suddenly died at the age of 15 years (Fig. 1). Case 4:
A 29-year-old Japanese male was observed to run much more slowly than his peers at age 6 years. He evinced marked limitation of neck flexion, limitation of extension of the elbows and weakness of the extremities at the age of 8, 295
Fig. 2. Transverse section of the right deltoid muscle of patient 3 showing variation in fiber size and degenerative changes of muscle fibers. Note cytoplasmic bodies (HE staining: X
Fig. 3. Electron micrograph showing cytoplasmic bodies and rod formation in patient 3 (X 2,000).
150).
bradycardia at the age of 10 and complete atrioventricular blocks on ECG at the age of 16. Symptoms were slowly progressive. The patient's brother who suffered from an identical neurological disorder with complete atrioventricular blocks was diagnosed as having Emery-Dreifuss muscular dystrophy. He died suddenly at the age of 18. Examinations showed normal intelligence, limitation of neck flexion, limitation of extension of both elbows and feet. The orbicularis oris and sternocleidomastoid muscles were weak. There was a mild to moderate degree of muscular weakness and atrophy, predominantly the proximal portion of the upper extremities and distal portion of the lower extremities. There were areflexia in all four extremities without pathological reflexes. Neither sensory impairment nor cerebellar signs were noted. Routine laboratory studies were normal except for the elevated creatine kinase level. The EMG revealed MUP of low amplitude and short duration, fibrillation potentials, positive sharp wave and full interference patterns. Histological and histochemical studies of the left deltoid muscle showed moderate variation in fiber size, moderate increases of endomysial and perimysial connective tissues, fiber splitting and rimmed vacuoles, but no mitochondrial abnormalities or raggedred fiber were found. Electron microscopic examinations revealed degenerative changes without specific abnormalities (Fig. 4). ECG showed complete atrioventricular blocks at a 296
rate of 40 beats per minute (Fig. 1). A cardiac pacemaker was inserted. Case 5: A 50-year-old Japanese male developed limitation of extension of the elbows and weakness of the lower extremities at the age of 12, and later developed weakness of the upper extremities and limitation of neck flexion. An abnormality in his ECG was noted at the age of 23, and he suffered cardiac arrest for several seconds at the age of 34. Symptoms were slowly progressive. The patient became non-ambulatory at the age of 38. He was an only child. No similar disorders were found in his family. Examination at the age of 44 showednormal intelligence, mildweakness of the orbicularis oculi and oris muscles, limitation of neck flexion, limitation of extension of the elbows, knees and feet and a moderate to severe degree of muscular weakness and atrophy in the extremities, predominantly the proximal portion of the upper extremities and distal portion of the lower extremities. Deep tendon reflexes were absent in all four extremities without pathological reflexes. Routine laboratory examinations were normal. EMG revealed MUP of low amplitude and short duration, fibrillation potentials, positive sharp wave and full interference patterns. Histological studies of the left quadriceps muscle showed moderate variation in fiber size, mild increases of endomysial and perimysial connective tissue and internal nuclei, but no mitochondrial abnor-
Fig. 4. Transverse section of the left deltoid muscle of patient 4 shows variation in fiber size, increased interstitial fibrous tissue and rimmed vacuoles (HE staining; X 150).
Fig. 5, Transverse section of the left quadriceps femoris muscle of patient 5 showing variation in fiber size, increased central nuclei and increased interstitial fibrous tissue (HE staining;
x lOO).
malities. Fiber type abnormalities or ragged-red fiber were not seen (Table 1, Fig. 5). Electron microscopic examination revealed degenerative changes without specific abnormalities. ECG showed an absence of P waves and junctional rhythm at a rate of 43 beats per minute (Fig. 1). The patient died suddenly at the age of 50. Discussion
Rigid spine syndrome and Emery-Dreifuss muscular dystrophy have characteristic clinical features, which distinguish them from other disorders. Rowland et al described five essential components of Emery-Dreifuss muscular dystrophy: the pattern of a sex-linked recessive inheritance, contractures at elbows and neck in childhood, distribution of weakness, affected biceps and triceps more than scapular muscles, and distal muscles earlier than proximal muscles in legs, very slow progression and cardiac conduction abnormalities leading ultimately to atrial arrest 12. Other authors also reported that EmeryDreifuss muscular dystrophy showed familial occurrence, sex-linked recessive or autosomal dominant trait, cardiac involvement with conduction defects and myogenic or neurogenic patterns in electromyograms and muscle biopsy 15-17. Patients 4 and 5 in our series evinced cardiac
conduction defects and showed familial or sporadic occurrence which is suggested to be a sex-linked recessive trait. These two patients are regarded as having Emery-Dreifuss muscular dystrophy, although they resemble the rigid spine syndrome, Rigid spine syndrome is usually a non-familial occurrence with a striking male predominance, although a few authors suggest that this syndrome may be a familial occurrence 11,13. Moreover, this syndrome does not usually entail cardiac conduction defects. Patients 1, 2 and 3 in our series are males and sporadic cases with onset in childhood, and they suffer no cardiac conduction defects. These three cases may thus be regarded as suffering from rigid spine syndrome, although it is not clear whether or not this syndrome is a different disorder than Emery-Dreifuss muscular dystrophy. Various clinical courses and histological findings in muscle biopsy specimens have been reported in the rigid spine syndrome. Patient 1 revealed a non-progressive clinical course and normal cardiac rhythm without conduction defects during the past 10 years. He is employed as an engineer. His muscle biopsy specimens showed mild myogenic changes without cytoplasmic bodies, membranous whorls or abnormal filaments, This case is considered as being a non-progressive case of the rigid spine syndrome. Patients 2 and 3 showed progressive clinical courses and died suddenly at the ages of 18 and 15, respectively. Patient 2 showed nor297
mal cardiac rhythm at the age of 13 and developed sinus tachycardia at a later stage. Patient 3 developed sinus tachycardia at the age of 15. Neither of these patients suffered from atrioventricular blocks. The two patients showed marked variations in fiber size of muscle fibers, moderate increases of connective tissues, internal nuclei and marked fiber necrosis which may suggest the rapid progression of muscle fiber degeneration. Electron microscopic examinations in these cases also showed massive collections of membranous whorls, cytoplasmic bodies and abnormal filaments in muscle specimens. These two cases are regarded as having a rapidly progressive course of rigid spine syndrome. At present, we conclude that the rigid spine syndrome may be distinguished from EmeryDreifuss muscular dystrophy by the absence or presence of a cardiac conduction defect. It will be necessary to study many cases with similar manifestations and to perform long-term followup studies on these cases to obtain further understanding of rigid spine syndrome and Emery-Dreifuss muscular dystrophy.
Acknowledgement This study was supported by Grant No. 85-04 from the National Center for Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare, Japan. The authors would like to thank Drs. Kitaguchi T, Nagasaka S, Muraoka S, Fukui R, Iwashita H and Ishihara Y for their help.
References DUBOWITZ V. Some unusual neuromuscular disorders. In: Walton JN, Canal N, Searlato G, eds. Muscle Diseases. Proceedings of an International Congress. Milan, 1969. Amsterdam, Excerpta Medica, 1970; 56873.
298
2 3
4 5
6
7
8
9
DUBOWITZV. Recent advances in neuromuscular disorders. Rheumatol Physic Med 1971; 11:126-30. DUBOWITZV, BROOKE MH. Muscle biopsy: A modern approach. In: Major problems in neurology, Vol 2, London, Saunders, 1973; 368-71. SEAY AR, ZITER FA, PETAJAN JH. Rigid spine syndrome: A type I fiber myopathy. Arch Neurol 1977; 34:119-22. GOEBEL HH, LENARD HG, GORKE W, KUNZE K. Fiber type disproportion in the rigid spine syndrome. Neurop~idiatrie 1977; 8:467-77. GOTO I, NAGASAKA S, NAGARA I4, K U R O I W A Y. Rigid spine syndrome. J Neurol Neurosurg Psychiatry 1979; 42:2769. GOTO 1, MURAOKA S, F u J n N, O/4TA M, KUROIWA Y. Rigid spine syndrome: Clinical and histological problems. J Neurol 1981; 226:143-8. COLVER AF, STEER CR, GODMAN MJ, UTTLEY WS, Rigid spine syndrome and fatal cardiomyopathie. Arch Dis Child 1981; 56:148-51. VOGELP, COEBELH/4, SEITZD. Rigid spine syndrome in a girl. J Neurol 1982; 228:259-65.
i0
MUSSINI JM~ MATH~ JF, PROST A, GRAY F, LABAT JJ, FEVE JR.
11
Le syndrome de la colonne raide. Un cas f~minin. Rev Neurol 1982; 138:25-37. POEWE W, WILLEIT H, SLUGA E, MAYR U. The rigid spine syndrome. A myopathy of uncertain nosological position. J Neurol Neurosurg Psychiatry 1985; 48:887-93.
12
ROWLAND LP, FETELL M, OLARTE M, HAYS A, SINGH N,
WANAT FE. Emery-Dreifuss muscular dystrophy. Ann Neurol 1979; 5:111-7. 13
14
15
16
17
SERRATRICE G, PELLISSIER JF, POUGET J, GASTAUT JL. L e
syndrome de la colonne vert~brale rigide et ses ffonti~res nosologiques. Deux observations. Presse Med 1984; 13:1129-32. FUKUI R, ISHIMOTO S, TABIRA T, GOTO I t KUROIWA Y. A case of the rigid spine syndrome associated with cytoplasmic bodies and rodlike particles. Clin Neuro11983; 23:531-8. EMERY AEH, DREIFUSS FE. Unusual type of benign X-linked muscular dystrophy. J Neurol Neurosurg Psychiatry 1966; 29:338-42. ROTrHAUWE HW, MORTIER W, BUYER H. Neuer Typ einer recessiv X-chromosomal vererbten Muskeldystrophie: Scapulo-humero-distale Muskeldystrophie mit frfihzeitigen Kontrakturen und Herzrhythmusst6rungen. Humangenetik 1972; 16:181200. HOPKINS LC, JACKSON JA, ELSAS LJ. Emery-Dreifuss humeroperoneal muscular dystrophy: An X-linked myopathy with unusual contractures and bradycardia. Ann Neurol 1981; 10:230-7.
Introduction Summary Rigid spine syndrome has been described by many authors ill. It usually has a childhood onset and affects males. The syndrome presents with limitation of neck and back flexion, joint contractures in elbows and feet. There is hardly any progression of weakness and atrophy in the extremities. The nosological entity of the rigid spine syndrome and Emery-Dreifuss muscular dystrophy has been discussed 1113. The purpose of this paper is to describe the clinical features and findings in rigid spine syndrome and Emery-Dreifuss muscular dystrophy.
Case reports Case 16: A 25-year-old Japanese male was observed to run more slowly than his peers at age 3 years. At age 6 years, a limitation of neck and back flexion and weakness of extremities were evident. There was no obvious progression of symptoms. Examination at the age of 16 years showed a high arched palate, mild scoliosis, limitation of neck flexion and a mild degree of limitation of extension of both elbows and knees. There was no intellectual impairment. The sternocleidomastoid muscles were weak and atrophic. There were a mild degree of muscular
We present five patients, three of whom suffered from a rigid spine syndrome and two from Emery-Dreifuss muscular dystrophy. One patient with rigid spine syndrome showed a nonprogressive course, normal cardiac rhythm and mild myopathic changes in muscle histology, while in the other two patients there was a rapidly progressive course, sinus tachycardia without cardiac conduction defects and marked fiber necrosis in muscle histology. The two patients suffering from EmeryDreifuss muscular dystrophy showed a very mildly progressing course, myopathic changes in muscle histology, cardiac conduction defects and deviations in electrocardiograms. These findings show that rigid spine syndrome can be distinguished from Emery-Dreifuss muscular dystrophy. Key words: Rigid spine syndrome, EmeryDreifuss muscular dystrophy, ECG.
weakness and atrophy and hypoactive reflexes without pathological reflexes in all four extremities. Neither sensory impairment nor cerebellar signs were found. Routine laboratory studies were normal except for an elevated serum creatine kinase level. There was no ankylosis nor any destructive process of the
* Department of Neurology, Neurological Institute, Faculty of Medicine, Kyushu University, Fukuoka, * * National Chikugo Hospital, Chikugo City, Fukuoka, Japan. Address for correspondence and reprint requests: Ikuo Goto, Department of Neurology, Neurological Institute, Faculty of Medicine, Kyushu University 60, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan 812. Accepted 10. 7.86 Clin Neurol Neurosurg 1986. Vol. 88-4.
293
Table 1. Synopsis of clinical and laboratory data of three cases of rigid spine syndrome and two cases of Emery Dreifuss muscular dystrophy. Patient Age (years), sex Clinical progression Age of onset (years) Consanguinity (first cousins) Family history Endocrine functions Creatine kinase (normal; < 70, * < 28) Muscle histology Fiber size variation Increases of connective tissues Increases of internal nuclei Fiber necrosis Electrocardiogram
25, male no worsening
18, male died, age 18
15, male died, age 15
29, male
6 +
6
6 +
6 +
(grandparents)
(grandparents)
normal 262
normal
(grandparents)
50, male died, age 50 12
+ normal 338
normal 693
+
+++
+
+--++
+
+ +++
+
normal rhythm
+ , very mild; + mild; + + , moderate; + + +
sinus taehycardia
+++ ++--+++ +++ +++
sinus tachycardia
294
normal 20*
++
++
++ +
+
complete atrioventricular blocks
++ +
absence of P waves, junctional rhythm
severe.
spine. EMG showed motor unit potentials (MUP) of low amplitude and short duration and full interference patterns without spontaneous discharge at rest. Histological and histochemical studies of the right biceps muscle revealed mild to moderate fiber size variability in both type 1 and type 2 fibers and mild increases in endomysial and perimysial connective tissues, but no vacuolar degeneration, inflammatory cell infiltration, mitochondrial abnormalities or ragged-red fiber were evident (Table 1). Electron microscopic examination showed no remarkable abnormality. ECG showed norrn"alrhythm with right axis deviation (Fig. 1). After ten years follow-up, the patient evinced no demonstrable worsening of muscle strength or contracture. ECG still showed normal rhythm with right axis deviation. Case 27: An 18-year-old Japanese boy developed limitation of neck flexion and extension of the elbows at the age of 6 years. The patient noticed weakness of the lower extremities at the age of 10 years and weakness of the upper extremities a year later. His symptoms were slowly progressive. Examination at the age of 13 years showed a high arched palate, low hairline, limitation of neck flexion and a mild degree of limitation of extension of both the elbows and the knees.
294
slow
Intelligence was normal. The sternocleidomastoid muscles were weak and atrophic. There was a mild to moderate degree of muscular weakness and atrophy, predominantly in the proximal portion of the extremities. There were hypoactive reflexes without pathological reflexes. Neither sensory impairment nor cerebellar signs were noted. Routine laboratory examinations were normal except for an elevated creatine kinase level. There was no destructive process of the spine. EMG revealed MUP of low amplitude and short duration, mild fibrillation potentials and full interference patterns. Histological and histochemical studies of the right biceps muscle showed marked variation in fiber size, mild increases in endomysial and perimysial connective tissues, central nuclei, degenerative changes in both type 1 and type 2 fibers, sarcoplasmic mass, phagocytosis, vacuolar degeneration and mild perivascular cell infiltrations, but no mitochondrial abnormalities or ragged-red fiber were seen. Electron microscopic examination revealed membranous whorls, cytoplasmic bodies and abnormal filaments. ECG was normal at the age of 13 (Fig. 1). The patient suffered from sinus tachycardia without conduction defect until he died suddenly at the age of 18 (Fig. 1).
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Fig. 1. E C G shows normal r h y t h m in patient 1, n o r m a l r h y t h m at age 13 and sinus tachycardia at age 18 in patient 2, sinus tachycardia in patient 3, complete atrioventricular blocks in patient 4 (intraatrial E C G shows A waves), and junctional r h y t h m and absence of P waves in patient 5.
Case 314: A 15-year-old Japanese boy showed mild weakness of the four extremities at the age of 6. His symptoms were slowly progressive. Neurological examination at the age of 15 revealed a high arched palate, marked limitation of neck flexion, contractures of the elbows and knees, scoliosis and deformity of the thorax. Mentation was normal. Diffuse and marked muscular weakness and atrophy were observable in the upper extremities and a mild to moderate degree of weakness and atrophy was found in the lower extremities, predominantly the proximal portion of the extremities. The sternocleidomastoid muscles were weak and atrophic. Deep tendon reflexes were all absent. Routine laboratory studies were normal except
for an elevated serum creatine kinase activity. EMG revealed MUP of low amplitude and short duration with no spontaneous discharge at rest. Muscle histology of the right deltoid showed marked variation in fiber size, moderate increases in endomysial and perimysial connective tissues, central nuclei, fiber splitting, ring fiber, sarcoplasmic mass, ghost fibers and mild to moderate cell infiltrations, but no mitochondrial abnormalities or ragged-red fiber were seen (Table 1, Fig. 2). Electron microscopic examination revealed membranous whorls, a lot of cytoplasmic bodies and rod-like particles (Fig. 3). The patient had suffered from sinus tachycardia without conduction defects during three months of follow-up, until he suddenly died at the age of 15 years (Fig. 1). Case 4:
A 29-year-old Japanese male was observed to run much more slowly than his peers at age 6 years. He evinced marked limitation of neck flexion, limitation of extension of the elbows and weakness of the extremities at the age of 8, 295
Fig. 2. Transverse section of the right deltoid muscle of patient 3 showing variation in fiber size and degenerative changes of muscle fibers. Note cytoplasmic bodies (HE staining: X
Fig. 3. Electron micrograph showing cytoplasmic bodies and rod formation in patient 3 (X 2,000).
150).
bradycardia at the age of 10 and complete atrioventricular blocks on ECG at the age of 16. Symptoms were slowly progressive. The patient's brother who suffered from an identical neurological disorder with complete atrioventricular blocks was diagnosed as having Emery-Dreifuss muscular dystrophy. He died suddenly at the age of 18. Examinations showed normal intelligence, limitation of neck flexion, limitation of extension of both elbows and feet. The orbicularis oris and sternocleidomastoid muscles were weak. There was a mild to moderate degree of muscular weakness and atrophy, predominantly the proximal portion of the upper extremities and distal portion of the lower extremities. There were areflexia in all four extremities without pathological reflexes. Neither sensory impairment nor cerebellar signs were noted. Routine laboratory studies were normal except for the elevated creatine kinase level. The EMG revealed MUP of low amplitude and short duration, fibrillation potentials, positive sharp wave and full interference patterns. Histological and histochemical studies of the left deltoid muscle showed moderate variation in fiber size, moderate increases of endomysial and perimysial connective tissues, fiber splitting and rimmed vacuoles, but no mitochondrial abnormalities or raggedred fiber were found. Electron microscopic examinations revealed degenerative changes without specific abnormalities (Fig. 4). ECG showed complete atrioventricular blocks at a 296
rate of 40 beats per minute (Fig. 1). A cardiac pacemaker was inserted. Case 5: A 50-year-old Japanese male developed limitation of extension of the elbows and weakness of the lower extremities at the age of 12, and later developed weakness of the upper extremities and limitation of neck flexion. An abnormality in his ECG was noted at the age of 23, and he suffered cardiac arrest for several seconds at the age of 34. Symptoms were slowly progressive. The patient became non-ambulatory at the age of 38. He was an only child. No similar disorders were found in his family. Examination at the age of 44 showednormal intelligence, mildweakness of the orbicularis oculi and oris muscles, limitation of neck flexion, limitation of extension of the elbows, knees and feet and a moderate to severe degree of muscular weakness and atrophy in the extremities, predominantly the proximal portion of the upper extremities and distal portion of the lower extremities. Deep tendon reflexes were absent in all four extremities without pathological reflexes. Routine laboratory examinations were normal. EMG revealed MUP of low amplitude and short duration, fibrillation potentials, positive sharp wave and full interference patterns. Histological studies of the left quadriceps muscle showed moderate variation in fiber size, mild increases of endomysial and perimysial connective tissue and internal nuclei, but no mitochondrial abnor-
Fig. 4. Transverse section of the left deltoid muscle of patient 4 shows variation in fiber size, increased interstitial fibrous tissue and rimmed vacuoles (HE staining; X 150).
Fig. 5, Transverse section of the left quadriceps femoris muscle of patient 5 showing variation in fiber size, increased central nuclei and increased interstitial fibrous tissue (HE staining;
x lOO).
malities. Fiber type abnormalities or ragged-red fiber were not seen (Table 1, Fig. 5). Electron microscopic examination revealed degenerative changes without specific abnormalities. ECG showed an absence of P waves and junctional rhythm at a rate of 43 beats per minute (Fig. 1). The patient died suddenly at the age of 50. Discussion
Rigid spine syndrome and Emery-Dreifuss muscular dystrophy have characteristic clinical features, which distinguish them from other disorders. Rowland et al described five essential components of Emery-Dreifuss muscular dystrophy: the pattern of a sex-linked recessive inheritance, contractures at elbows and neck in childhood, distribution of weakness, affected biceps and triceps more than scapular muscles, and distal muscles earlier than proximal muscles in legs, very slow progression and cardiac conduction abnormalities leading ultimately to atrial arrest 12. Other authors also reported that EmeryDreifuss muscular dystrophy showed familial occurrence, sex-linked recessive or autosomal dominant trait, cardiac involvement with conduction defects and myogenic or neurogenic patterns in electromyograms and muscle biopsy 15-17. Patients 4 and 5 in our series evinced cardiac
conduction defects and showed familial or sporadic occurrence which is suggested to be a sex-linked recessive trait. These two patients are regarded as having Emery-Dreifuss muscular dystrophy, although they resemble the rigid spine syndrome, Rigid spine syndrome is usually a non-familial occurrence with a striking male predominance, although a few authors suggest that this syndrome may be a familial occurrence 11,13. Moreover, this syndrome does not usually entail cardiac conduction defects. Patients 1, 2 and 3 in our series are males and sporadic cases with onset in childhood, and they suffer no cardiac conduction defects. These three cases may thus be regarded as suffering from rigid spine syndrome, although it is not clear whether or not this syndrome is a different disorder than Emery-Dreifuss muscular dystrophy. Various clinical courses and histological findings in muscle biopsy specimens have been reported in the rigid spine syndrome. Patient 1 revealed a non-progressive clinical course and normal cardiac rhythm without conduction defects during the past 10 years. He is employed as an engineer. His muscle biopsy specimens showed mild myogenic changes without cytoplasmic bodies, membranous whorls or abnormal filaments, This case is considered as being a non-progressive case of the rigid spine syndrome. Patients 2 and 3 showed progressive clinical courses and died suddenly at the ages of 18 and 15, respectively. Patient 2 showed nor297
mal cardiac rhythm at the age of 13 and developed sinus tachycardia at a later stage. Patient 3 developed sinus tachycardia at the age of 15. Neither of these patients suffered from atrioventricular blocks. The two patients showed marked variations in fiber size of muscle fibers, moderate increases of connective tissues, internal nuclei and marked fiber necrosis which may suggest the rapid progression of muscle fiber degeneration. Electron microscopic examinations in these cases also showed massive collections of membranous whorls, cytoplasmic bodies and abnormal filaments in muscle specimens. These two cases are regarded as having a rapidly progressive course of rigid spine syndrome. At present, we conclude that the rigid spine syndrome may be distinguished from EmeryDreifuss muscular dystrophy by the absence or presence of a cardiac conduction defect. It will be necessary to study many cases with similar manifestations and to perform long-term followup studies on these cases to obtain further understanding of rigid spine syndrome and Emery-Dreifuss muscular dystrophy.
Acknowledgement This study was supported by Grant No. 85-04 from the National Center for Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare, Japan. The authors would like to thank Drs. Kitaguchi T, Nagasaka S, Muraoka S, Fukui R, Iwashita H and Ishihara Y for their help.
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