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Skeletal muscle involvement in Escobar syndrome
Skeletal Muscle Involvement in Escobar Syndrome Kenji Yokochi, MD, Sei Suzuki, MD, Toyotaka Tanaka, MD, Mie Asada, MD and Ikuya Nonaka, MD In addition to the clinical characteristics of Escobar syndrome, including an anomalous facial expression, multiple joint contractures, multiple pterygia and a short stature, two female siblings developed proximal dominant muscle weakness from birth and slowly progressive scoliosis. Biopflied specimens obtained from the paravertebral and gluteus maxim us muscles at the time of spinal surgery showed variation in fiber size, increased numbers of fibers with central nuclei, interstitial fibrosis and disorganized intermyofibrillar networks with occasional core/targetoid formations. The most outstanding histochemical abnormality in both cases was an abnormal fiber type distribution (type 2 fiber deficiency) which might be the result of an abnormal or deficient neural supply to the developing muscles. The defective neural influence on the muscle is assumed to produce the above-mentioned muscle changes, inducing multiple joint contractures and scoliosis. Yokochi K, Suzuki S, Tanaka T, Asada M, Nonaka 1. Skeletal muscle involvement in escobar syndrome. Brain Dev 1985; 7:585-9
It is well known that an anomalous condition of multiple pterygia involving the neck, axillae, elbows and knees is occasionally associated with growth retardation, facial abnormalities and multiple joint contractures [1-10]. Escobar et al [1] reported a 12-year-old patient and reviewed 19 well documented cases in the literature diagnosed as pterygium syndrome [4-6], Bonnevie-Ullrich syndrome [7] and arthrogryposis multiplex congenita [8-10] . They proposed that the condition might be a dis-
From the Department of Pediatrics, Nagoya City University Medical School, Nagoya (KY); Departments of Pediatrics (KY) and Orthopedics (SS, TT, MA); National Rehabilitation Center for Disabled Children, Tokyo; Division of Ultrastructural Research, National Center for Nervous, Mental and Muscular Disorders, Kodaira, Tokyo (IN). Received for publication: April 16, 1985. Accepted for publication: July 24, 1985.
Key words: Escobar syndrome, type 1 fiber predominance, core/targetoid formation, congenital myopathy. Correspondence address: Dr. Kenji Yokochi, Department of Pediatrics, Seirei-Mikatabara Hospital, Mikatabara-machi 3453, Hamamatsu 433, Shizuoka, Japan.
tinct clinical entity inherited as an autosomal recessive trait. In his textbook entitled "Recognizable patterns of human malformation", Smith [11] described this entity under the name of Escobar syndrome. Little is known about the pathogenetic mechanism which causes the multiple joint contractures in this syndrome. Since three examined muscles showed muscle fiber degeneration and disorganization of myofibrils [9, 12, 13], myopathic changes in skeletal muscle have been considered to be responsible for the induction of flexion contractures of multiple joints. In one patient, mild type 1 fiber predominance with hypertrophic type 2 fibers was recognized on histochemical examination [2]. In order to clarify whether the muscle abnormality is a neuropathic, myopathi~ or anomalous state, we examined biopsied muscles from two female siblings who had clinical characteristics of Escobar syndrome by histochemical and electron microscopic methods. Case Reportss Two female siblings were admitted to our
A
B
Fig 1 The characteristic facial expression, mUltiple joint -contractures, multiple pterygia and short stature in Case 1 (AJ and Case 2 (BJ.
hospital because of gait disturbance and scoliosis at the ages of 15 and 12 years, respectively. The parents were second cousins and had only the two affected children described in this report. There was no neuromuscular disease in the family members.
low-set ears, micrognathia, down-turned corners of the mouth and a high-arched palate. Her genital labia majora were hypoplastic. In addition to multiple pterygia (neck , axillae and feet), joint contractures and marked scoliosis, she had mild muscle weakness and atrophy with a predilection for the proximal part of the extremities. The deep tendon reflexes were hypoactive with no pathologic reaction . Fasciculation, sensory disturbance and cranial nerve abnormality were not observed . On laboratory examination, serum creatine kinase (CK) was found to be 45 lU/L (normal: 18-86), the nerve conduction velocity (MCV) of the tibial nerve was 48.6 m/sec, and the electromyogram (EMC) of biceps brachii and quadriceps femoris showed no abnormality . The skull and skeletal bones showed no particular abnormalities in an X-ray study.
Case 2 (the younger sister of Case 1) Her clinical history was almost the same as that in Case 1, including decreased fetal movement during pregnancy, multiple joint contractu res (hips, knees and elbows) from birth, difficulty in swallowing during the neonatal period and Case 1 (the eldersister) delayed developmental milestones. She obHer mother felt a decrease in fetal movement tained head control at 5 months, sat alone during pregnancy. She was delivered by cesare- at 15 months and shuffled at 3 years of age. an section at full term because of a narrow After surgical correcti~n of hip flexion-contracpelvis. Her birth weight was 2,500 gm. At tures at 5 years, she started to walk with a birth, she already had bilateral contractu res waddling gait. She stood up with Cowers' of the hip and knee joints in flexion, campto- maneuver. Her scoliosis progressively worsened . dactyly and pes equinus. During the neonatal Her mental development was normal. On admission at 12 years, she was also a period, she was fed through a nasogastric tube because of difficulty in swallowing. Her motor small girl, of 119 cm height and 22 kg weight development was delayed; she obtained head (Fig 1B). Her facial expression was also charactcontrol at 6 months, sat alone at 12 months and eristic of Escobar syndrome. Her labia majora walked with support at 2 years when she was were hypoplastic. She had multiple pterygia, noted to have mild proximal dominant muscle bilateral flexion-contractures of the hip and weakness. She underwent operative correction elbow joints, pes equinu~ and left convex of the contracted hip joint at 3 years of age. scoliosis. She also had mild muscle weakness At 4 years she began to walk alone with a and atrophy like Case l. On laboratory examination, CK was found waddling gait. She stood up with Cowers' maneuver. Thereafter her scoliosis progres- to be 33 lU/L, MCV of the right tibial nerve sively worsened. Her mental development was was 46.8 m/sec and the EMC of biceps brachii normal. and quadriceps femoris showed no abnormality. On admission at 15 years, she was a small An X-ray study of the skeletal system showed and intelligent girl of 125 cm height and 25 kg normal bony structures. weight (Fig lA). She had the characteristic facial expression of Escobar syndrome including epicanthal folds, antimongoloid palpebral Muscle Pathology fissures , ptosis, hypertelorism , a long philtrum, At the time of surgery for correction of scolio-
586 Brain & Development, Vol 7, No 6, 1985
Fig 2 The paravertebral muscle from Case 1. Notable variation in fiber size, moderate endomysial fibrosis and a number of fibers with internally placed nuclei (A) . Note markedly disorganized myofibrillar networks forming occasional core/targetoid formations. All muscle fibers are stained darkly, i.e. behaving as type 1 (B) . A :H&E, B: NADH-TR , Bar = 50}./,.
~t'.~- 'fl~'!;-'I~
sis, paravertebral muscle in convex apex was obtained from Case 1, and both paravertebral in convex apex and gluteus maximus muscles from Case 2 for histologic and histochemical evaluation. The muscles were frozen in isopentane cooled with liquid nitrogen. Serial frozen sections were stained by a battery of histochemical methods. Small portions of the biopsied specimens were processed for electron microscopic examination.
Case 1 There was moderate variation in fiber size, they ranged from 30 to 100 microns in diameter. The individual fibers were embedded in mildly to moderately proliferated connective tissue .
Fig 3 An electron micrograph of the muscle from Case 1. Severely disarrayed myofibrils with Z• streaming in the upper fiber and relatively well preserved band structures in the lower one. x5,500 (Bar =2}./,).
No apparent necrotic or regenerating fibers were identified. A number of fibers had internally , mostly centrally, placed nuclei (Fig 2A). Neither ragged-red fibers nor nemaline bodies were recognized on modified Gomori trichrome staining. On NADH-tetrazolium reductase (NADH-TR) staining, almost all muscle fibers were stained darkly (type 1 fibers) and they had disorganized intermyofibrillar networks with a moth-eaten appearance , and target and targetoidjcore structures which were usually located at the periphery of the sarcoplasm (Fig 2B). On ATPase staining, 97% of the muscle fibers behaved as type 1 and 3% as type 2A with a complete lack of type 2B and 2C fibers . Other stainings including periodic Yokochi et al: Muscle in Escobar syndrome 587
Fig 4 The paravertebral muscle from Case 2. There is a marked variation in fiber size with numerous hypertrophic fibers having disorganized intermyofibrillar networks. NADH-TR, Bar = SOil.
acid-Schiff (PAS), oil red 0, acid and alkaline phosphatases, acetylcholinesterase, nonspecific esterase, phosphorylase, phosphofructokinase, cytochrome c oxidase and AMP-deaminase showed no particular abnormal findings. On electron microscopic examination, the most outstanding feature was disarrayed myofibrils with a loss of striation and occasional Z-streaming in a number of fibers (Fig 3).
Case 2 The muscle pathology in Case 2 was almost the same as that in Case 1; moderate variation in fiber size with some hypertrophic fibers, mild endo- and perimysial fibrosis, an increased number of fibers with central nuclei (approximately 30%), and an absence of necrotic and regenerating processes. On NADH staining, intermyofibrillar networks were seen to be more severely disorganized than in Case 1, they had a snake-coil, moth-eaten and core/targetoid appearance in the paravertebral muscle (Fig 4). All muscle fibers in both paravertebral and gluteus maximus muscles were recognized to be type 1 (complete type 2 fiber deficiency) on ATPase staining. Other routine histochemical examinations disclosed no particular abnormalities. The electron microscopic morphology was almost the same as that in Case 1. Comments The two sisters described in the present report had an anomalous facial expression, multiple pterygia, multiple joint contractures, hypoplastic external genitalia and a short stature which coincide with the characteristics of
588 Brain & Development, Vol 7, No 6, 1985
. Escobar syndrome [1] . In addition, the striking clinical features in the patients included muscle weakness with difficulty in swallowing from birth and delayed developmental milestones. Although muscle involvement was described in the previous reports, much attention was not paid to the pathogenetic mechanism of the muscle alterations. Muscle involvement is assumed to be a constant feature in this syndrome because most patients (15 of 19 patients) had multiple joint contractures associated with scoliosis (6 of 19 patients) and delayed developmental milestones [1] . Since there were no groups of atrophic fibers or small angular fibers suggesting a denervating process, the muscle pathology seen in the present biopsies can be regarded as being "myopathic" as in previous reports [9, 12, 13]. Although the patients had normal serum CK levels and no necrotic or regenerating processes in the muscles, progressive muscular dystrophy of the congenital form (CMD) cannot be ruled out, because degenerative process in CMD is occasionally too slow to show apparent clinical progression and elevated enzyme levels [14, 15]. The other outstanding histochemical feature of the biopsied muscles was an abnormal fiber type distribution, typ~ 2 fiber deficiency. Type 1 fiber predominance (with occasional type 2 fiber deficiency) is a constant feature in congenital nonprogressive myopathies, especially in central core disease and nemaline myopathy [14]. While the core/targetoid structures in the present muscles were located at the periphery of the sarcoplasm, the overall muscle histochemistry is very close to that of central core disease [14, 16]. Myopathic changes including variation in fiber size, core formation and abnormal fiber type distribution are recognizable in the paraspinal and gluteal muscles of the patients with idiopathic scoliosis [1719]. In such patients, an undiagnosed or milder form of congenital myopathy is assumed to present causing a prominent spinal deformity [18]. A preferential paraspinal muscle involvement as seen in the present patients may be the common feature in various congenital myopathies including congenital muscular dystrophy [20] and some congenital non-progressive myopathies [14, 21]. It is well known that undifferentiated type 2C fibers differentiate into well differentiated
type r, 2A or 2B fibers after innervation by different types of motor neurons during the fetal and early infantile stages [22]. If type 2 motoneurons are absent or maldeveloped, type 1 fiber predominance as seen in various congenital myopathies may ensue [14]. Therefore, the muscle alterations in Escobar syndrome, at least in part, might result from an abnormal neural influence upon the developing muscles which produces a "myopathic" muscle pathology with a strikingly abnormal fiber type distribution. References 1. Escobar V, Bixler D, Gleiser S, Weaver DD, Gibbs T. Multiple pterygium syndrome. Am J Dis Child 1978,132:609-11. 2. Chen H, Chang CH, Misra RP, Peters HA, Grijalva NS, Opitz JM. Multiple pterygium syndrome. Am J Med Genet 1980;7:91-102. 3. Penchaszadeh VB, Salszberg B. Multiple pterygium syndrome. J Med Genet 1981;18:451-5. 4. Scott C. Pterygium syndrome. Birth Defects 1969;5:231-2. 5. Norum RA, James VL, Mabry CC. Pterygium syndrome in three children in a recessive pedigree pattern. Birth Defects 1969;5:233-5. 6. Aarskog D. Pterygium syndrome. Birth Defects 1971;7:232-4. 7. Rossi E, Caflisch A. Le syndrome du pterygium: status Bonnevie-Ullrich dystrophia brevicolli congenita. Helv Paediatr Acta 1951;6: 119-48. 8. Martischnig Von E, Swoboda W. Arthrogryposis multiplex congenita und Pterygiumsyndrom (Ein Fall von Pterygoarthromyodysplasia congenita).
Monatsschr Kinderheilkd 1952;100:22-5. 9. Lang K, Lelbach WK, Colmant HJ. Beitrag zum Bilde der Pterygomyodysplasia arthrogrypotica
10. 11. 12. 13. 14. 15. 16.
17. 18. 19. 20. 21. 22.
generalis (Pterygo-arthromyodysplasia congenita). Monatsschr Kinderheilkd 1960;108:248-52. Srivastava RN. Arthrogryposis multiplex congenita: case report of two siblings. Clin Pediatr 1968;7:691-4. Smith DW. Escobar syndrome. Recognizable patterns of human malformation. Philadelphia: Saunders, 1982:228. Herbich VJ. Zur Frage der Arthrogryposis multiplex congenita und des Status Bonnevie-Ullrich. Monatsschr Kinderheilkd 1952; 100: 25-7. Kanof A, Aronson SM, Yolk BW. Arthrogryposis: a clinical and pathologic study of three cases. Pediatrics 1956;17:532-40. Dubowitz V. Muscle disease in childhood. London: Saunders, 1978. McMenamin JB, Becker LE, Murphy EG. Congenital muscular dystrophy: a clinicopathologic report of 24 cases. J Pediatr 1982; 100:692-7. Isaacs H, Heffron JJA, Badenhorst M. Central core disease. A correlated genetic, histochemical, ultramicroscopic and biochemical study. J Neurol Neurosurg Psychiatry 1975;38: 1177-86. Spencer GSG, Zorab PA. Spinal muscle in scoliosis. Part 1. Histology and histochemistry. J Neurol Sci 1976 ;30: 137-42. Yarom R, Robin GC. Studies on spinal and peripheral muscle from patients with scoliosis. Spine 1979;4: 12-21. Sahgal V, Shah A, Flanagan N et al. Morphologic and morphometric studies of muscle in idiopathic scoliosis. Acta Orthoped Scand 1983;54:242-51. Yokochi K, Tanaka T, Nonaka I. Congenital muscular dystrophy manifesting severe infantile scoliosis. Brain Dev 1985;7:492-5. Seay AR, Ziter FA, Petajan JH. Rigid spine syndrome. A type 1 fiber myopathy. Arch Neurol 1977;34: 119-22. Brooke MH, Williamson E, Kaiser KK. The behaviour of four fiber types in developing and reinnervated muscle. Arch Neurol 1971;25: 360-6.
Yokochi et al: Muscle in Escobar syndrome 589
It is well known that an anomalous condition of multiple pterygia involving the neck, axillae, elbows and knees is occasionally associated with growth retardation, facial abnormalities and multiple joint contractures [1-10]. Escobar et al [1] reported a 12-year-old patient and reviewed 19 well documented cases in the literature diagnosed as pterygium syndrome [4-6], Bonnevie-Ullrich syndrome [7] and arthrogryposis multiplex congenita [8-10] . They proposed that the condition might be a dis-
From the Department of Pediatrics, Nagoya City University Medical School, Nagoya (KY); Departments of Pediatrics (KY) and Orthopedics (SS, TT, MA); National Rehabilitation Center for Disabled Children, Tokyo; Division of Ultrastructural Research, National Center for Nervous, Mental and Muscular Disorders, Kodaira, Tokyo (IN). Received for publication: April 16, 1985. Accepted for publication: July 24, 1985.
Key words: Escobar syndrome, type 1 fiber predominance, core/targetoid formation, congenital myopathy. Correspondence address: Dr. Kenji Yokochi, Department of Pediatrics, Seirei-Mikatabara Hospital, Mikatabara-machi 3453, Hamamatsu 433, Shizuoka, Japan.
tinct clinical entity inherited as an autosomal recessive trait. In his textbook entitled "Recognizable patterns of human malformation", Smith [11] described this entity under the name of Escobar syndrome. Little is known about the pathogenetic mechanism which causes the multiple joint contractures in this syndrome. Since three examined muscles showed muscle fiber degeneration and disorganization of myofibrils [9, 12, 13], myopathic changes in skeletal muscle have been considered to be responsible for the induction of flexion contractures of multiple joints. In one patient, mild type 1 fiber predominance with hypertrophic type 2 fibers was recognized on histochemical examination [2]. In order to clarify whether the muscle abnormality is a neuropathic, myopathi~ or anomalous state, we examined biopsied muscles from two female siblings who had clinical characteristics of Escobar syndrome by histochemical and electron microscopic methods. Case Reportss Two female siblings were admitted to our
A
B
Fig 1 The characteristic facial expression, mUltiple joint -contractures, multiple pterygia and short stature in Case 1 (AJ and Case 2 (BJ.
hospital because of gait disturbance and scoliosis at the ages of 15 and 12 years, respectively. The parents were second cousins and had only the two affected children described in this report. There was no neuromuscular disease in the family members.
low-set ears, micrognathia, down-turned corners of the mouth and a high-arched palate. Her genital labia majora were hypoplastic. In addition to multiple pterygia (neck , axillae and feet), joint contractures and marked scoliosis, she had mild muscle weakness and atrophy with a predilection for the proximal part of the extremities. The deep tendon reflexes were hypoactive with no pathologic reaction . Fasciculation, sensory disturbance and cranial nerve abnormality were not observed . On laboratory examination, serum creatine kinase (CK) was found to be 45 lU/L (normal: 18-86), the nerve conduction velocity (MCV) of the tibial nerve was 48.6 m/sec, and the electromyogram (EMC) of biceps brachii and quadriceps femoris showed no abnormality . The skull and skeletal bones showed no particular abnormalities in an X-ray study.
Case 2 (the younger sister of Case 1) Her clinical history was almost the same as that in Case 1, including decreased fetal movement during pregnancy, multiple joint contractu res (hips, knees and elbows) from birth, difficulty in swallowing during the neonatal period and Case 1 (the eldersister) delayed developmental milestones. She obHer mother felt a decrease in fetal movement tained head control at 5 months, sat alone during pregnancy. She was delivered by cesare- at 15 months and shuffled at 3 years of age. an section at full term because of a narrow After surgical correcti~n of hip flexion-contracpelvis. Her birth weight was 2,500 gm. At tures at 5 years, she started to walk with a birth, she already had bilateral contractu res waddling gait. She stood up with Cowers' of the hip and knee joints in flexion, campto- maneuver. Her scoliosis progressively worsened . dactyly and pes equinus. During the neonatal Her mental development was normal. On admission at 12 years, she was also a period, she was fed through a nasogastric tube because of difficulty in swallowing. Her motor small girl, of 119 cm height and 22 kg weight development was delayed; she obtained head (Fig 1B). Her facial expression was also charactcontrol at 6 months, sat alone at 12 months and eristic of Escobar syndrome. Her labia majora walked with support at 2 years when she was were hypoplastic. She had multiple pterygia, noted to have mild proximal dominant muscle bilateral flexion-contractures of the hip and weakness. She underwent operative correction elbow joints, pes equinu~ and left convex of the contracted hip joint at 3 years of age. scoliosis. She also had mild muscle weakness At 4 years she began to walk alone with a and atrophy like Case l. On laboratory examination, CK was found waddling gait. She stood up with Cowers' maneuver. Thereafter her scoliosis progres- to be 33 lU/L, MCV of the right tibial nerve sively worsened. Her mental development was was 46.8 m/sec and the EMC of biceps brachii normal. and quadriceps femoris showed no abnormality. On admission at 15 years, she was a small An X-ray study of the skeletal system showed and intelligent girl of 125 cm height and 25 kg normal bony structures. weight (Fig lA). She had the characteristic facial expression of Escobar syndrome including epicanthal folds, antimongoloid palpebral Muscle Pathology fissures , ptosis, hypertelorism , a long philtrum, At the time of surgery for correction of scolio-
586 Brain & Development, Vol 7, No 6, 1985
Fig 2 The paravertebral muscle from Case 1. Notable variation in fiber size, moderate endomysial fibrosis and a number of fibers with internally placed nuclei (A) . Note markedly disorganized myofibrillar networks forming occasional core/targetoid formations. All muscle fibers are stained darkly, i.e. behaving as type 1 (B) . A :H&E, B: NADH-TR , Bar = 50}./,.
~t'.~- 'fl~'!;-'I~
sis, paravertebral muscle in convex apex was obtained from Case 1, and both paravertebral in convex apex and gluteus maximus muscles from Case 2 for histologic and histochemical evaluation. The muscles were frozen in isopentane cooled with liquid nitrogen. Serial frozen sections were stained by a battery of histochemical methods. Small portions of the biopsied specimens were processed for electron microscopic examination.
Case 1 There was moderate variation in fiber size, they ranged from 30 to 100 microns in diameter. The individual fibers were embedded in mildly to moderately proliferated connective tissue .
Fig 3 An electron micrograph of the muscle from Case 1. Severely disarrayed myofibrils with Z• streaming in the upper fiber and relatively well preserved band structures in the lower one. x5,500 (Bar =2}./,).
No apparent necrotic or regenerating fibers were identified. A number of fibers had internally , mostly centrally, placed nuclei (Fig 2A). Neither ragged-red fibers nor nemaline bodies were recognized on modified Gomori trichrome staining. On NADH-tetrazolium reductase (NADH-TR) staining, almost all muscle fibers were stained darkly (type 1 fibers) and they had disorganized intermyofibrillar networks with a moth-eaten appearance , and target and targetoidjcore structures which were usually located at the periphery of the sarcoplasm (Fig 2B). On ATPase staining, 97% of the muscle fibers behaved as type 1 and 3% as type 2A with a complete lack of type 2B and 2C fibers . Other stainings including periodic Yokochi et al: Muscle in Escobar syndrome 587
Fig 4 The paravertebral muscle from Case 2. There is a marked variation in fiber size with numerous hypertrophic fibers having disorganized intermyofibrillar networks. NADH-TR, Bar = SOil.
acid-Schiff (PAS), oil red 0, acid and alkaline phosphatases, acetylcholinesterase, nonspecific esterase, phosphorylase, phosphofructokinase, cytochrome c oxidase and AMP-deaminase showed no particular abnormal findings. On electron microscopic examination, the most outstanding feature was disarrayed myofibrils with a loss of striation and occasional Z-streaming in a number of fibers (Fig 3).
Case 2 The muscle pathology in Case 2 was almost the same as that in Case 1; moderate variation in fiber size with some hypertrophic fibers, mild endo- and perimysial fibrosis, an increased number of fibers with central nuclei (approximately 30%), and an absence of necrotic and regenerating processes. On NADH staining, intermyofibrillar networks were seen to be more severely disorganized than in Case 1, they had a snake-coil, moth-eaten and core/targetoid appearance in the paravertebral muscle (Fig 4). All muscle fibers in both paravertebral and gluteus maximus muscles were recognized to be type 1 (complete type 2 fiber deficiency) on ATPase staining. Other routine histochemical examinations disclosed no particular abnormalities. The electron microscopic morphology was almost the same as that in Case 1. Comments The two sisters described in the present report had an anomalous facial expression, multiple pterygia, multiple joint contractures, hypoplastic external genitalia and a short stature which coincide with the characteristics of
588 Brain & Development, Vol 7, No 6, 1985
. Escobar syndrome [1] . In addition, the striking clinical features in the patients included muscle weakness with difficulty in swallowing from birth and delayed developmental milestones. Although muscle involvement was described in the previous reports, much attention was not paid to the pathogenetic mechanism of the muscle alterations. Muscle involvement is assumed to be a constant feature in this syndrome because most patients (15 of 19 patients) had multiple joint contractures associated with scoliosis (6 of 19 patients) and delayed developmental milestones [1] . Since there were no groups of atrophic fibers or small angular fibers suggesting a denervating process, the muscle pathology seen in the present biopsies can be regarded as being "myopathic" as in previous reports [9, 12, 13]. Although the patients had normal serum CK levels and no necrotic or regenerating processes in the muscles, progressive muscular dystrophy of the congenital form (CMD) cannot be ruled out, because degenerative process in CMD is occasionally too slow to show apparent clinical progression and elevated enzyme levels [14, 15]. The other outstanding histochemical feature of the biopsied muscles was an abnormal fiber type distribution, typ~ 2 fiber deficiency. Type 1 fiber predominance (with occasional type 2 fiber deficiency) is a constant feature in congenital nonprogressive myopathies, especially in central core disease and nemaline myopathy [14]. While the core/targetoid structures in the present muscles were located at the periphery of the sarcoplasm, the overall muscle histochemistry is very close to that of central core disease [14, 16]. Myopathic changes including variation in fiber size, core formation and abnormal fiber type distribution are recognizable in the paraspinal and gluteal muscles of the patients with idiopathic scoliosis [1719]. In such patients, an undiagnosed or milder form of congenital myopathy is assumed to present causing a prominent spinal deformity [18]. A preferential paraspinal muscle involvement as seen in the present patients may be the common feature in various congenital myopathies including congenital muscular dystrophy [20] and some congenital non-progressive myopathies [14, 21]. It is well known that undifferentiated type 2C fibers differentiate into well differentiated
type r, 2A or 2B fibers after innervation by different types of motor neurons during the fetal and early infantile stages [22]. If type 2 motoneurons are absent or maldeveloped, type 1 fiber predominance as seen in various congenital myopathies may ensue [14]. Therefore, the muscle alterations in Escobar syndrome, at least in part, might result from an abnormal neural influence upon the developing muscles which produces a "myopathic" muscle pathology with a strikingly abnormal fiber type distribution. References 1. Escobar V, Bixler D, Gleiser S, Weaver DD, Gibbs T. Multiple pterygium syndrome. Am J Dis Child 1978,132:609-11. 2. Chen H, Chang CH, Misra RP, Peters HA, Grijalva NS, Opitz JM. Multiple pterygium syndrome. Am J Med Genet 1980;7:91-102. 3. Penchaszadeh VB, Salszberg B. Multiple pterygium syndrome. J Med Genet 1981;18:451-5. 4. Scott C. Pterygium syndrome. Birth Defects 1969;5:231-2. 5. Norum RA, James VL, Mabry CC. Pterygium syndrome in three children in a recessive pedigree pattern. Birth Defects 1969;5:233-5. 6. Aarskog D. Pterygium syndrome. Birth Defects 1971;7:232-4. 7. Rossi E, Caflisch A. Le syndrome du pterygium: status Bonnevie-Ullrich dystrophia brevicolli congenita. Helv Paediatr Acta 1951;6: 119-48. 8. Martischnig Von E, Swoboda W. Arthrogryposis multiplex congenita und Pterygiumsyndrom (Ein Fall von Pterygoarthromyodysplasia congenita).
Monatsschr Kinderheilkd 1952;100:22-5. 9. Lang K, Lelbach WK, Colmant HJ. Beitrag zum Bilde der Pterygomyodysplasia arthrogrypotica
10. 11. 12. 13. 14. 15. 16.
17. 18. 19. 20. 21. 22.
generalis (Pterygo-arthromyodysplasia congenita). Monatsschr Kinderheilkd 1960;108:248-52. Srivastava RN. Arthrogryposis multiplex congenita: case report of two siblings. Clin Pediatr 1968;7:691-4. Smith DW. Escobar syndrome. Recognizable patterns of human malformation. Philadelphia: Saunders, 1982:228. Herbich VJ. Zur Frage der Arthrogryposis multiplex congenita und des Status Bonnevie-Ullrich. Monatsschr Kinderheilkd 1952; 100: 25-7. Kanof A, Aronson SM, Yolk BW. Arthrogryposis: a clinical and pathologic study of three cases. Pediatrics 1956;17:532-40. Dubowitz V. Muscle disease in childhood. London: Saunders, 1978. McMenamin JB, Becker LE, Murphy EG. Congenital muscular dystrophy: a clinicopathologic report of 24 cases. J Pediatr 1982; 100:692-7. Isaacs H, Heffron JJA, Badenhorst M. Central core disease. A correlated genetic, histochemical, ultramicroscopic and biochemical study. J Neurol Neurosurg Psychiatry 1975;38: 1177-86. Spencer GSG, Zorab PA. Spinal muscle in scoliosis. Part 1. Histology and histochemistry. J Neurol Sci 1976 ;30: 137-42. Yarom R, Robin GC. Studies on spinal and peripheral muscle from patients with scoliosis. Spine 1979;4: 12-21. Sahgal V, Shah A, Flanagan N et al. Morphologic and morphometric studies of muscle in idiopathic scoliosis. Acta Orthoped Scand 1983;54:242-51. Yokochi K, Tanaka T, Nonaka I. Congenital muscular dystrophy manifesting severe infantile scoliosis. Brain Dev 1985;7:492-5. Seay AR, Ziter FA, Petajan JH. Rigid spine syndrome. A type 1 fiber myopathy. Arch Neurol 1977;34: 119-22. Brooke MH, Williamson E, Kaiser KK. The behaviour of four fiber types in developing and reinnervated muscle. Arch Neurol 1971;25: 360-6.
Yokochi et al: Muscle in Escobar syndrome 589