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Type 1 fiber size disproportion: morphometric data from 37 children with myopathic, neuropathic, or idiopathic
S T Iannaccone1, K E Bove, C A Vogler
1Division of Pediatric Neurology, Children's Hospital Medical Center, Cincinnati, Ohio.
Insights
Fiber size disproportion (FSD) in infants with hypotonia often indicates muscle maturation delay. FSD can resolve or persist, with neuronal dysfunction playing a key role in its varied causes.
Area of Science:
- Pediatric Neurology
- Muscle Histopathology
- Developmental Pediatrics
Background:
- Infants with hypotonia and developmental delay can exhibit fiber size disproportion (FSD), characterized by small type 1 muscle fibers.
- FSD is a histological finding that requires further investigation into its underlying causes and clinical implications.
Purpose of the Study:
- To analyze clinical and quantitative muscle biopsy data in infants with hypotonia and developmental delay associated with FSD.
- To determine the etiological factors, clinical course, and diagnostic criteria for FSD in pediatric patients.
Main Methods:
- Review of clinical data and muscle biopsy specimens from 37 pediatric patients diagnosed with FSD between 1971 and 1985.
- Quantitative analysis of muscle fiber size, classification of FSD into myopathic, neuropathic, or benign maturation delay categories.
- Longitudinal observation of FSD and clinical outcomes in sequential biopsies.
Main Results:
- FSD was prevalent in infants over 2 months old, with variable progression (resolution, persistence, or intensification) over time.
- In some cases, hypotonia regressed and development normalized, with concurrent FSD resolution, though type 1 fiber predominance often remained.
- FSD was classified as myopathic (15), neuropathic (17, with 6 having perinatal asphyxia), or benign maturation delay (5); morphometric criteria did not consistently differentiate these groups.
- Type 1 fibers were typically small and type 2 fibers hypertrophied, irrespective of classification.
Conclusions:
- Fiber size disproportion (FSD) represents a delay in muscle maturation with diverse etiologies.
- Neuronal dysfunction is suggested as a significant factor in FSD pathogenesis, particularly in neuropathic cases.
- Morphometric analysis alone is insufficient to definitively distinguish between congenital myopathy with FSD, neuropathic FSD, and benign maturation delay.
Abstract:
We reviewed clinical data and quantitative muscle biopsy data from infants with hypotonia and developmental delay who had relatively small type 1 muscle fibers (fiber size disproportion; FSD). Study material consisted of 49 thigh muscle specimens from 37 patients, 1 week to 11.5 years old, who had FSD diagnosed between 1971 and 1985. Beyond 2 months of age, FSD was greater than 12% in at least one biopsy from all but 2 patients. In sequential specimens obtained from 11 patients, we observed that FSD may resolve, persist unchanged, or intensify with age. In 6 patients, hypotonia regressed, and development tended to normalize during 1-4 years of observation; FSD resolved in 4 cases, but numerical predominance of type 1 fibers persisted in 3 of them. In a small group designated congenital myopathy with FSD only, the disproportion in fiber diameter persisted unchanged or intensified with time and was more severe after the age of 6 months than in the other subgroups. We classified FSD as definitely or probably myopathic (15 cases), definitely or probably neuropathic (17 cases), and benign maturation delay (5 cases). Six of 17 neuropathic cases had a history of perinatal asphyxia. In most cases, type 1 fibers were absolutely small and type 2 fibers were hypertrophied, independent of classification. FSD is a manifestation of muscle maturation delay of variable etiology. The prevalence of nervous system disorders in our series suggests that neuronal dysfunction plays an important role in pathogenesis. We were unable to define morphometric criteria that consistently distinguished congenital myopathy with FSD from definable neuropathic FSD or from benign maturation delay.