Case reportCentral core disease and congenital neuromuscular disease with uniform type 1 fibers in one family
Introduction
There are many patients with congenital myopathy in whom two different disease-specific morphologic abnormalities may coexist. Also, there may be morphological differences from patient to patient within the same family. There have been families with central core disease (CCD) in a daughter, and CCD and nemaline bodies in her mother [1], and CCD and nemaline bodies in the mother and only nemaline bodies in her two sons [2]. These cases indicate that the same mutation for congenital myopathy may result in heterogeneous pathologic phenotypes, i.e. different or overlapping abnormalities. Therefore the classification of congenital myopathies based on pathologic characteristics will have to be modified when the gene defects in individual diseases are identified.
In this paper we report a father with CCD and his first son with congenital neuromuscular disease with uniform type 1 fibers (CNMDU1).
Section snippets
Clinical summaries
Patient 1: This male patient, aged 27 years, was the second son of non-consanguineous healthy parents. His motor milestones were delayed and he learned to walk alone at 3 years of age. He had been aware of his muscle weakness, because he had been unable to perform strenuous work or run fast.
His elder brother had no muscle weakness. He had three sons. The first (patient 2) and third (patient 3) sons had muscle symptoms, but the second was healthy.
On examination, he exhibited mild predominantly
DNA analysis
We extracted DNA from frozen muscle samples from patients 1 and 2, and sequenced exons 1–18 and 44–47 in the ryanodine receptor gene, where most of the mutations in CCD and malignant hyperthermia patients have been found. No mutation was found in the above regions in our patients.
Discussion
This is the first report of CCD and CNMDU1 in one family. The disease in this family was probably inherited as an autosomal dominant trait. CNMDU1 was proposed to be a new congenital myopathy by Oh et al. [3]. In previously reported cases of CNMDU1 [3], [4], [5], there were no nemaline rods, central nuclei or core structures, but over 99% of the muscle fibers were type 1 ones. Some patients exhibited severely delayed motor milestones and muscle weakness [4], [5], but our patients had only mild
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A review of core myopathy: central core disease, multiminicore disease, dusty core disease, and core-rod myopathy
2021, Neuromuscular DisordersCitation Excerpt :Interestingly, young patients in families with pathologically confirmed typical CCD sometimes show extreme type 1 fiber predominance or uniform type 1 fiber but no cores; therefore, these patients are sometimes diagnosed with congenital neuromuscular disease with uniform type 1 fiber (CNMDU1). The presence of such patients in the same family suggests that fiber-type conversion precedes core formation in disease development (Fig. 1A–F) [32,33]. The cores are most likely formed at the periphery of muscle fibers and then extend longitudinally toward the central region [7,34].
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