MCID: MNC011
MIFTS: 31

Minicore Myopathy with External Ophthalmoplegia

Categories: Genetic diseases, Rare diseases, Neuronal diseases

Aliases & Classifications for Minicore Myopathy with External Ophthalmoplegia

MalaCards integrated aliases for Minicore Myopathy with External Ophthalmoplegia:

Name: Minicore Myopathy with External Ophthalmoplegia 57 53 75 13 73
Multiminicore Disease with External Ophthalmoplegia 57 53 75
Minicore Myopathy 57 29 6
Multicore Myopathy with External Ophthalmoplegia 53 75
Multiminicore Myopathy Multicore Myopathy with External Ophthalmoplegia 57
Congenital Multicore Myopathy with External Ophthalmoplegia 59
Myopathy, Minicore, External Ophthalmoplegia 40
Multicore Myopathy 57
Mmdo 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset in neonatal period or early infancy
some patients have lethal fetal akinesia with death in utero
findings in muscle biopsy may be variable


HPO:

32
minicore myopathy with external ophthalmoplegia:
Onset and clinical course phenotypic variability neonatal onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


Summaries for Minicore Myopathy with External Ophthalmoplegia

OMIM : 57 Multiminicore disease (MMD) is an inherited neuromuscular disorder defined pathologically by the presence of multiple areas of reduced mitochondrial oxidative activity running along a limited extent of the longitudinal axis of the muscle fiber, so-called 'minicores.' These regions show sarcomere disorganization and mitochondria depletion. Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present. MMD is a pathologic diagnosis and shows clinical and genetic heterogeneity. Affected individuals have clinical features of a congenital myopathy, including neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy, which may progress slowly or remain stable (Ferreiro and Fardeau, 2002). Patients with recessive mutations in the RYR1 gene typically show severe congenital muscular dystrophy with ophthalmoplegia, although there is phenotypic variability. Some patients may present in utero with fetal akinesia, arthrogryposis, and lung hypoplasia resulting in fetal or perinatal death (McKie et al., 2014). Skeletal muscle biopsy of patients with recessive RYR1 mutations show variable features, including central cores (Jungbluth et al., 2007), congenital fiber-type disproportion (CFTD) (Monnier et al., 2009), and centronuclear myopathy (Wilmshurst et al., 2010). (255320)

MalaCards based summary : Minicore Myopathy with External Ophthalmoplegia, also known as multiminicore disease with external ophthalmoplegia, is related to multicore myopathy with mental retardation, short stature, and hypogonadotropic hypogonadism and minicore myopathy, antenatal onset, with arthrogryposis, and has symptoms including edema, ophthalmoplegia and facial paresis. An important gene associated with Minicore Myopathy with External Ophthalmoplegia is RYR1 (Ryanodine Receptor 1). Affiliated tissues include lung and skeletal muscle, and related phenotypes are high palate and ptosis

UniProtKB/Swiss-Prot : 75 Multiminicore disease with external ophthalmoplegia: Clinically heterogeneous neuromuscular disorder. General features include neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy, which may progress slowly or remain stable. Muscle biopsy shows multiple, poorly circumscribed, short areas of sarcomere disorganization and mitochondria depletion (areas termed minicores) in most muscle fibers. Typically, no dystrophic signs, such as muscle fiber necrosis or regeneration or significant endomysial fibrosis, are present in multiminicore disease.

Related Diseases for Minicore Myopathy with External Ophthalmoplegia

Diseases related to Minicore Myopathy with External Ophthalmoplegia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 multicore myopathy with mental retardation, short stature, and hypogonadotropic hypogonadism 12.1
2 minicore myopathy, antenatal onset, with arthrogryposis 12.1
3 rigid spine muscular dystrophy 1 11.4
4 multiminicore disease 11.4

Symptoms & Phenotypes for Minicore Myopathy with External Ophthalmoplegia

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
external ophthalmoplegia affecting upward and lateral gaze

Skeletal Spine:
scoliosis

Neurologic Peripheral Nervous System:
areflexia

Head And Neck Face:
myopathic facies
facial weakness

Neurologic Central Nervous System:
delayed motor development
some patients only achieve sitting

Laboratory Abnormalities:
normal serum creatine kinase

Prenatal Manifestations Movement:
reduced fetal movements

Respiratory:
respiratory insufficiency
frequent respiratory infections
lung hypoplasia
respiratory impairment

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
hydrops

Muscle Soft Tissue:
increased connective tissue
exercise-induced myalgia
proximal muscle weakness
axial muscle weakness
muscle weakness, diffuse
more
Skeletal:
ligamentous laxity

Abdomen Gastrointestinal:
poor feeding

Head And Neck Mouth:
high-arched palate (rare)
inverted v-shaped mouth


Clinical features from OMIM:

255320

Human phenotypes related to Minicore Myopathy with External Ophthalmoplegia:

32 (show all 29)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 ptosis 32 HP:0000508
3 muscular hypotonia 32 HP:0001252
4 respiratory insufficiency 32 HP:0002093
5 scoliosis 32 HP:0002650
6 facial palsy 32 HP:0010628
7 recurrent respiratory infections 32 HP:0002205
8 neonatal hypotonia 32 HP:0001319
9 feeding difficulties in infancy 32 HP:0008872
10 generalized muscle weakness 32 HP:0003324
11 skeletal muscle atrophy 32 HP:0003202
12 hydrops fetalis 32 HP:0001789
13 nemaline bodies 32 occasional (7.5%) HP:0003798
14 joint laxity 32 HP:0001388
15 polyhydramnios 32 HP:0001561
16 areflexia 32 HP:0001284
17 decreased fetal movement 32 HP:0001558
18 motor delay 32 HP:0001270
19 muscular dystrophy 32 HP:0003560
20 increased connective tissue 32 HP:0009025
21 myopathic facies 32 HP:0002058
22 external ophthalmoplegia 32 HP:0000544
23 exercise-induced myalgia 32 HP:0003738
24 pulmonary hypoplasia 32 HP:0002089
25 proximal muscle weakness 32 HP:0003701
26 increased variability in muscle fiber diameter 32 HP:0003557
27 axial muscle weakness 32 HP:0003327
28 difficulty running 32 HP:0009046
29 type 1 and type 2 muscle fiber minicore regions 32 HP:0003787

UMLS symptoms related to Minicore Myopathy with External Ophthalmoplegia:


edema, ophthalmoplegia, facial paresis, generalized muscle weakness, exercise-induced myalgia

Drugs & Therapeutics for Minicore Myopathy with External Ophthalmoplegia

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Molecular and Genetic Studies of Congenital Myopathies Recruiting NCT00272883
2 Congenital Muscle Disease Study of Patient and Family Reported Medical Information Recruiting NCT01403402

Search NIH Clinical Center for Minicore Myopathy with External Ophthalmoplegia

Genetic Tests for Minicore Myopathy with External Ophthalmoplegia

Genetic tests related to Minicore Myopathy with External Ophthalmoplegia:

# Genetic test Affiliating Genes
1 Minicore Myopathy 29 RYR1

Anatomical Context for Minicore Myopathy with External Ophthalmoplegia

MalaCards organs/tissues related to Minicore Myopathy with External Ophthalmoplegia:

41
Lung, Skeletal Muscle

Publications for Minicore Myopathy with External Ophthalmoplegia

Articles related to Minicore Myopathy with External Ophthalmoplegia:

# Title Authors Year
1
Multi-minicore myopathy: a clinical and histopathological study of 17 cases. ( 17594595 )
2007
2
Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene. ( 16380615 )
2005
3
Adult onset multi/minicore myopathy associated with a mutation in the RYR1 gene. ( 14999498 )
2004

Variations for Minicore Myopathy with External Ophthalmoplegia

UniProtKB/Swiss-Prot genetic disease variations for Minicore Myopathy with External Ophthalmoplegia:

75
# Symbol AA change Variation ID SNP ID
1 RYR1 p.Arg109Trp VAR_032910 rs118192173
2 RYR1 p.Met2423Lys VAR_032915 rs118192174
3 RYR1 p.Met402Thr VAR_063846 rs118192117
4 RYR1 p.His2035Leu VAR_063847 rs367543056
5 RYR1 p.Asn3326Lys VAR_063848 rs367543057
6 RYR1 p.Cys3402Gly VAR_063849 rs367543058

ClinVar genetic disease variations for Minicore Myopathy with External Ophthalmoplegia:

6
(show all 28)
# Gene Variation Type Significance SNP ID Assembly Location
1 RYR1 NM_000540.2(RYR1): c.6502G> A (p.Val2168Met) single nucleotide variant Pathogenic rs118192176 GRCh37 Chromosome 19, 38985219: 38985219
2 RYR1 NM_000540.2(RYR1): c.6502G> A (p.Val2168Met) single nucleotide variant Pathogenic rs118192176 GRCh38 Chromosome 19, 38494579: 38494579
3 RYR1 NM_000540.2(RYR1): c.14545G> A (p.Val4849Ile) single nucleotide variant Pathogenic rs118192168 GRCh37 Chromosome 19, 39071043: 39071043
4 RYR1 NM_000540.2(RYR1): c.14545G> A (p.Val4849Ile) single nucleotide variant Pathogenic rs118192168 GRCh38 Chromosome 19, 38580403: 38580403
5 RYR1 NM_000540.2(RYR1): c.14647-1449A> G single nucleotide variant Pathogenic rs193922886 GRCh37 Chromosome 19, 39074134: 39074134
6 RYR1 NM_000540.2(RYR1): c.14647-1449A> G single nucleotide variant Pathogenic rs193922886 GRCh38 Chromosome 19, 38583494: 38583494
7 RYR1 NM_000540.2(RYR1): c.325C> T (p.Arg109Trp) single nucleotide variant Pathogenic/Likely pathogenic rs118192173 GRCh37 Chromosome 19, 38934252: 38934252
8 RYR1 NM_000540.2(RYR1): c.325C> T (p.Arg109Trp) single nucleotide variant Pathogenic/Likely pathogenic rs118192173 GRCh38 Chromosome 19, 38443612: 38443612
9 RYR1 NM_000540.2(RYR1): c.7268T> A (p.Met2423Lys) single nucleotide variant Pathogenic rs118192174 GRCh37 Chromosome 19, 38990601: 38990601
10 RYR1 NM_000540.2(RYR1): c.7268T> A (p.Met2423Lys) single nucleotide variant Pathogenic rs118192174 GRCh38 Chromosome 19, 38499961: 38499961
11 RYR1 NM_000540.2(RYR1): c.14365-2A> T single nucleotide variant Pathogenic rs193922870 GRCh37 Chromosome 19, 39070620: 39070620
12 RYR1 NM_000540.2(RYR1): c.14365-2A> T single nucleotide variant Pathogenic rs193922870 GRCh38 Chromosome 19, 38579980: 38579980
13 RYR1 NM_000540.2(RYR1): c.10343C> T (p.Ser3448Phe) single nucleotide variant Pathogenic rs193922836 GRCh37 Chromosome 19, 39013751: 39013751
14 RYR1 NM_000540.2(RYR1): c.10343C> T (p.Ser3448Phe) single nucleotide variant Pathogenic rs193922836 GRCh38 Chromosome 19, 38523111: 38523111
15 RYR1 NM_000540.2(RYR1): c.1739_1742dupATCA (p.His581Glnfs) duplication Pathogenic rs193922771 GRCh37 Chromosome 19, 38946339: 38946342
16 RYR1 NM_000540.2(RYR1): c.1739_1742dupATCA (p.His581Glnfs) duplication Pathogenic rs193922771 GRCh38 Chromosome 19, 38455699: 38455702
17 RYR1 NM_000540.2(RYR1): c.10348-6C> G single nucleotide variant Pathogenic/Likely pathogenic rs193922837 GRCh37 Chromosome 19, 39013851: 39013851
18 RYR1 NM_000540.2(RYR1): c.10348-6C> G single nucleotide variant Pathogenic/Likely pathogenic rs193922837 GRCh38 Chromosome 19, 38523211: 38523211
19 RYR1 NM_000540.2(RYR1): c.14126C> T (p.Thr4709Met) single nucleotide variant Pathogenic/Likely pathogenic rs118192140 GRCh37 Chromosome 19, 39063944: 39063944
20 RYR1 NM_000540.2(RYR1): c.14126C> T (p.Thr4709Met) single nucleotide variant Pathogenic/Likely pathogenic rs118192140 GRCh38 Chromosome 19, 38573304: 38573304
21 RYR1 NM_000540.2(RYR1): c.7042_7044delGAG (p.Glu2348del) deletion Pathogenic,risk factor rs121918596 GRCh38 Chromosome 19, 38499649: 38499651
22 RYR1 NM_000540.2(RYR1): c.7042_7044delGAG (p.Glu2348del) deletion Pathogenic,risk factor rs121918596 GRCh37 Chromosome 19, 38990289: 38990291
23 RYR1 NM_000540.2(RYR1): c.7063C> T (p.Arg2355Trp) single nucleotide variant Pathogenic rs193922803 GRCh38 Chromosome 19, 38499670: 38499670
24 RYR1 NM_000540.2(RYR1): c.7063C> T (p.Arg2355Trp) single nucleotide variant Pathogenic rs193922803 GRCh37 Chromosome 19, 38990310: 38990310
25 RYR1 NM_001042723.1(RYR1): c.6721C> T (p.Arg2241Ter) single nucleotide variant Pathogenic rs200563280 GRCh37 Chromosome 19, 38987106: 38987106
26 RYR1 NM_001042723.1(RYR1): c.6721C> T (p.Arg2241Ter) single nucleotide variant Pathogenic rs200563280 GRCh38 Chromosome 19, 38496466: 38496466
27 RYR1 NM_000540.2(RYR1): c.2097_2123del27 (p.Glu699_Gly707del) deletion Pathogenic rs876661306 GRCh38 Chromosome 19, 38458222: 38458248
28 RYR1 NM_000540.2(RYR1): c.2097_2123del27 (p.Glu699_Gly707del) deletion Pathogenic rs876661306 GRCh37 Chromosome 19, 38948862: 38948888

Expression for Minicore Myopathy with External Ophthalmoplegia

Search GEO for disease gene expression data for Minicore Myopathy with External Ophthalmoplegia.

Pathways for Minicore Myopathy with External Ophthalmoplegia

GO Terms for Minicore Myopathy with External Ophthalmoplegia

Sources for Minicore Myopathy with External Ophthalmoplegia

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