Minicore myopathy

Goknur Haliloglu MD (Dr. Haliloglu of Hacettepe Children's Hospital in Ankara, Turkey, has no relevant financial relationships to disclose.)
Haluk Topaloglu MD (

Dr. Topaloglu of Hacettepe Children's Hospital in Ankara, Turkey, has no relevant financial relationships to disclose.

Harvey B Sarnat MD FRCPC MS, editor. (

Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.

Originally released June 16, 1995; last updated January 22, 2017; expires January 22, 2020
Notice: This article has expired and is therefore not available for CME credit.

This article includes discussion of minicore myopathy, minicore disease, multiminicore myopathy, and minicore-multicore myopathies. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Minicore myopathy is a congenital myopathy within the group of core myopathies that is most commonly caused by recessive mutations in the RYR1 and SEPN1 genes. It has been linked to dominant mutations in the gene for beta-myosin heavy chain protein (MYH7) and autosomal recessive mutations of titin (TTN). A number of distinct phenotypes are seen in minicore myopathy. Recessive mutations of satellite cell gene (MEGF10) are defined in patients with early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARRD). Advances in clinical and genetic characterization of minicore myopathy have revealed an expanded clinical spectrum, with a minority of affected children presenting in early infancy with severe muscle weakness. Minicore myopathy has been associated with an atypical periodic paralysis syndrome, distally predominant weakness, and cardiomyopathy, further widening the clinical spectrum of this disorder. Recessive variants and dominant mutations in the gene encoding the alpha-1 subunit of the dihydropyridine receptor (CACNA1S) are described; however, functional studies are required to clarify the role of these mutations.

Key points


• Core myopathies collectively represent the largest group of congenital myopathies, including central core disease, multiminicore diseases, and atypical cores.


• Multiminicore disease presents with weakness throughout life, although predominantly in childhood.


• Muscle histology shows presence of multiple cores within a myofiber cross section, not particularly well demarcated, giving a “mouth-eaten” appearance.


• Major causes are recessively inherited mutations in the genes encoding selenoprotein N (SEPN1) and RYR1.


• Other rare causes are recessive mutations in TTN, MEGF10, and CACNA1S; and there are dominant mutations in MYH7 and CACNA1S.


• There may be a continuum between multiminicore and central core diseases; patients and carriers with certain missense mutations in RYR1 are at risk of malignant hyperthermia and should be evaluated accordingly.


• Head lag and neck flexor weakness may evolve to rigid spine deformity. Patients with rigid spine deformity and scoliosis should be managed in terms of early respiratory insufficiency and nocturnal hypoventilation.


• Other rare presentations include atypical periodic paralysis syndrome, distal weakness and cardiomyopathy.

Historical note and terminology

The congenital myopathies are a heterogeneous group of disorders with a variable natural history; examples include central core disease (Magee and Shy 1956), nemaline myopathy (Shy et al 1963), and centronuclear (myotubular) myopathy (Spiro et al 1966). In 1966, Engel and Gomez described a nonprogressive congenital myopathy in which muscle fibers showed (by electron microscopy) multiple focal defects of oxidative and myofibrillar ATPase enzymatic activities and disorganization of myofilaments. This condition was soon recognized as a separate entity within the childhood myopathies, distinct from central core disease, and became known as “minicore” or “multicore” myopathy, now sometimes referred to as “multiminicore disease” (Engel and Gomez 1966; Engel et al 1971).

Minicore myopathy was previously considered a relatively benign condition, but it is now recognized to be frequently associated with progressive kyphoscoliosis and respiratory insufficiency. Cardiomyopathy is another potentially serious, but uncommon, complication of minicore disease (Shuaib et al 1988; Cullup et al 2012).

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