Elsevier

Brain and Development

Volume 22, Issue 4, 1 June 2000, Pages 262-264
Brain and Development

Case report
Central core disease and congenital neuromuscular disease with uniform type 1 fibers in one family

https://doi.org/10.1016/S0387-7604(00)00108-XGet rights and content

Abstract

We report a family in which the father had central core disease and his son had congenital neuromuscular disease with uniform type 1 fibers. This is the first report of such a combination. Although they had no recognized mutation in the ryanodine receptor gene, it is highly likely that the son also had central core disease but without core structures. The absence of cores may be due to the muscle sample or the young age of the patient since core structures have been reported to increase with age. Although the prevalence of core structures in individual muscles is unknown, there is a possibility of sampling error. In some patients, congenital neuromuscular disease with uniform type 1 fibers is closely related to or identical with central core disease.

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

References (10)

  • A.K. Afifi et al.

    Congenital non-progressive myopathy: central core disease and nemaline myopathy in one family

    Neurology

    (1965)
  • J.L. Casado et al.

    Congenital myopathy with cores and nemaline rods in one family

    Neurologia

    (1995)
  • S.J. Oh et al.

    Non-progressive congenital neuromuscular disease with uniform type 1 fiber

    Arch Neurol

    (1983)
  • G. Pellegrini et al.

    A case of congenital neuromuscular disease with uniform type 1 fibers, abnormal mitochondrial network and jagged Z-line

    Neuropediatrics

    (1985)
  • A. Araki et al.

    Congenital neuromuscular disease with uniform type 1 fibers: a case report (in Japanese)

    No To Hattatsu (Tokyo)

    (1991)
There are more references available in the full text version of this article.

Cited by (20)

  • A review of core myopathy: central core disease, multiminicore disease, dusty core disease, and core-rod myopathy

    2021, Neuromuscular Disorders
    Citation 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].

  • Hypotonia and Weakness: Level of the Muscle

    2018, Volpe's Neurology of the Newborn
View all citing articles on Scopus
View full text