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Congenital myopathies
Correspondence
References
[1] S h i m o m u r a C, Nonaka 1. Nemaline myopathy: Comparative muscle histochemistry in the severe neonatal, moderate congenital, and adult-onset forms. Pediatr Neurol 1989;5:25-31. [2] Iannaeeone ST, Bove KE, Vogler CA, Buchino J J. Type I fiber size disproportion: Morphometric data from 37 children with myopathic, neuropathic, or idiopathic hypotonia. Pediatr Pathol 1987;7:395-419.
CONGENITAL MYOPATHIES To the Editor."
Shimomura and Nonaka have contributed yet another scholarly work toward our understanding of the congenital myopathies [ 1]. Their finding of type 1 fiber smallness (disproportion) and predominance in severe nemaline myopathy is similar to our own results [2]. The large number of patients they studied enabled them to correlate their findings to clinical severity and course. We also demonstrated by repeat biopsy that nemaline myopathy may be a progressive disease with histochemical abnormalities, such as poor reaction to myosin ATPase, which increase with age, time, or both. We agree with their opinion that the small type 1 fibers and type 2c fibers are consistent with the interpretation that nemaline myopathy is associated with immaturity or delay in maturation of skeletal muscle. This interpretation does not necessarily mean that the pathogenesis is related to abnormal innervation. We found similar abnormalities of fiber type distribution and diameter in patients with muscular dystrophy and other disorders. All of these patients had myopathic electrophysiologic studies; however, abnormalities of innervation could occur in primary myopathies, such as with interruption of sarcolemmal integrity. We agree with the possibility that defective motor neuron interaction with developing muscle would be a pathogenesis common to all disorders in which fiber size disproportion has been found [2]. Shimomura and Nonaka have presented a large group of patients with a rare form of congenital myopathy [ 1]. Would they relate their clinical and morphologic findings to the genetic inheritance pattern or linkage studies of their patients?
We greatly appreciate Dr. lannaccone's comments on our study of nemaline myopathy. We would like to reply to her question about the family data of our patients. Of the 22 patients with nemaline myopathy we studied, 3 were familial (Figs 1A-1C). No linkage analysis was performed in any of the families. In family 7, there were 3 affected members (Fig 1B). If we assume that the condition in this family is a single-factor inheritance disease, a mutant gene would have been transmitted through an unaffected father (III-I 1) to his daughter (IV-I) and son (IV-2). This pedigree is not consistent with X-linked inheritance, but suggests an autosomal-dominant mode of inheritance with incomplete penetrance. The pedigree of family 19, in which the parents are consanguineous, favors autosomal-recessive inheritance (Fig 1C). Multifactorial inheritance cannot be eliminated in any of the 3 pedigrees. In family 1, the elder sister (lI-1) suffers from the moderate congenital form, while the younger brother suffers from the severe neonatal form (Fig 1A). These family data may indicate that the nemaline myopathy is etiologically heterogeneous, although pathogenesis may be common in its 3 forms suggested in our previous study as well as by Dr. Iannaccone. In addition, the data indicated that a clinical form does not relate to an inheritance pattern.
Susan T. Iannaccone, MD University of Cincinnati Medical Center Cincinnati, Ohio
Chieko Shimomura, MD Nagasaki University School of Medicine Nagasaki, Japan
1
I
0
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2
Moderate congenital form •
1
It
III
IV
1
tr12
<>~4
18
Severe neonatal form
2
OTD
I
II
To the Editor:
la i.1~o
11
I 12 #
I 13
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4
6,°
2o
Moderate congenital form Congenital heart disease (C.H,D,) Moderate congenital form + C,H.D,
/
B
1
l
2
®
Moderate congenital form
/ Figure 1. Pedigrees of 3 families with nemaline myopathy. Arrows indicate probands and asterisks denote patients presented in our previous report. Family numbers correspond to the patient numbers in our previous report." (A) family 1; (B) family 7; and (C) family 19.
66
PEDIATRIC NEUROLOGY
Vol. 6 No. 1
References
[1] S h i m o m u r a C, Nonaka 1. Nemaline myopathy: Comparative muscle histochemistry in the severe neonatal, moderate congenital, and adult-onset forms. Pediatr Neurol 1989;5:25-31. [2] Iannaeeone ST, Bove KE, Vogler CA, Buchino J J. Type I fiber size disproportion: Morphometric data from 37 children with myopathic, neuropathic, or idiopathic hypotonia. Pediatr Pathol 1987;7:395-419.
CONGENITAL MYOPATHIES To the Editor."
Shimomura and Nonaka have contributed yet another scholarly work toward our understanding of the congenital myopathies [ 1]. Their finding of type 1 fiber smallness (disproportion) and predominance in severe nemaline myopathy is similar to our own results [2]. The large number of patients they studied enabled them to correlate their findings to clinical severity and course. We also demonstrated by repeat biopsy that nemaline myopathy may be a progressive disease with histochemical abnormalities, such as poor reaction to myosin ATPase, which increase with age, time, or both. We agree with their opinion that the small type 1 fibers and type 2c fibers are consistent with the interpretation that nemaline myopathy is associated with immaturity or delay in maturation of skeletal muscle. This interpretation does not necessarily mean that the pathogenesis is related to abnormal innervation. We found similar abnormalities of fiber type distribution and diameter in patients with muscular dystrophy and other disorders. All of these patients had myopathic electrophysiologic studies; however, abnormalities of innervation could occur in primary myopathies, such as with interruption of sarcolemmal integrity. We agree with the possibility that defective motor neuron interaction with developing muscle would be a pathogenesis common to all disorders in which fiber size disproportion has been found [2]. Shimomura and Nonaka have presented a large group of patients with a rare form of congenital myopathy [ 1]. Would they relate their clinical and morphologic findings to the genetic inheritance pattern or linkage studies of their patients?
We greatly appreciate Dr. lannaccone's comments on our study of nemaline myopathy. We would like to reply to her question about the family data of our patients. Of the 22 patients with nemaline myopathy we studied, 3 were familial (Figs 1A-1C). No linkage analysis was performed in any of the families. In family 7, there were 3 affected members (Fig 1B). If we assume that the condition in this family is a single-factor inheritance disease, a mutant gene would have been transmitted through an unaffected father (III-I 1) to his daughter (IV-I) and son (IV-2). This pedigree is not consistent with X-linked inheritance, but suggests an autosomal-dominant mode of inheritance with incomplete penetrance. The pedigree of family 19, in which the parents are consanguineous, favors autosomal-recessive inheritance (Fig 1C). Multifactorial inheritance cannot be eliminated in any of the 3 pedigrees. In family 1, the elder sister (lI-1) suffers from the moderate congenital form, while the younger brother suffers from the severe neonatal form (Fig 1A). These family data may indicate that the nemaline myopathy is etiologically heterogeneous, although pathogenesis may be common in its 3 forms suggested in our previous study as well as by Dr. Iannaccone. In addition, the data indicated that a clinical form does not relate to an inheritance pattern.
Susan T. Iannaccone, MD University of Cincinnati Medical Center Cincinnati, Ohio
Chieko Shimomura, MD Nagasaki University School of Medicine Nagasaki, Japan
1
I
0
[]
2
Moderate congenital form •
1
It
III
IV
1
tr12
<>~4
18
Severe neonatal form
2
OTD
I
II
To the Editor:
la i.1~o
11
I 12 #
I 13
[]
4
6,°
2o
Moderate congenital form Congenital heart disease (C.H,D,) Moderate congenital form + C,H.D,
/
B
1
l
2
®
Moderate congenital form
/ Figure 1. Pedigrees of 3 families with nemaline myopathy. Arrows indicate probands and asterisks denote patients presented in our previous report. Family numbers correspond to the patient numbers in our previous report." (A) family 1; (B) family 7; and (C) family 19.
66
PEDIATRIC NEUROLOGY
Vol. 6 No. 1