MCID: MNC011
MIFTS: 30

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 53 49 71 28 13 69
Multiminicore Disease with External Ophthalmoplegia 53 49 71
Multicore Myopathy with External Ophthalmoplegia 49 71
Multiminicore Myopathy Multicore Myopathy with External Ophthalmoplegia 53
Congenital Multicore Myopathy with External Ophthalmoplegia 55
Multicore Myopathy 53
Minicore Myopathy 53
Mmdo 71

Characteristics:

OMIM:

53
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:

31
minicore myopathy with external ophthalmoplegia:
Onset and clinical course phenotypic variability neonatal onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare neurological diseases


Summaries for Minicore Myopathy with External Ophthalmoplegia

OMIM : 53 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 joint laxity, generalized muscle weakness and exercise-induced myalgia. An important gene associated with Minicore Myopathy with External Ophthalmoplegia is RYR1 (Ryanodine Receptor 1). Affiliated tissues include lung and skeletal muscle.

UniProtKB/Swiss-Prot : 71 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:

53
MuscleSoftTissue:
exercise-induced myalgia
increased connective tissue
proximal muscle weakness
axial muscle weakness
muscle weakness, diffuse
more
Respiratory:
respiratory insufficiency
frequent respiratory infections
lung hypoplasia
respiratory impairment

PrenatalManifestationsAmnioticFluid:
polyhydramnios
hydrops

HeadAndNeckFace:
myopathic facies
facial weakness

NeurologicCentralNervousSystem:
delayed motor development
some patients only achieve sitting

LaboratoryAbnormalities:
normal serum creatine kinase

PrenatalManifestationsMovement:
reduced fetal movements

HeadAndNeckEyes:
ptosis
external ophthalmoplegia affecting upward and lateral gaze

SkeletalSpine:
scoliosis

NeurologicPeripheralNervousSystem:
areflexia

Skeletal:
ligamentous laxity

AbdomenGastrointestinal:
poor feeding

HeadAndNeckMouth:
high-arched palate (rare)
inverted v-shaped mouth


Clinical features from OMIM:

255320

Human phenotypes related to Minicore Myopathy with External Ophthalmoplegia:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 joint laxity 31 HP:0001388
2 generalized muscle weakness 31 HP:0003324
3 exercise-induced myalgia 31 HP:0003738
4 high palate 31 HP:0000218
5 ptosis 31 HP:0000508
6 respiratory insufficiency 31 HP:0002093
7 scoliosis 31 HP:0002650
8 facial palsy 31 HP:0010628
9 recurrent respiratory infections 31 HP:0002205
10 neonatal hypotonia 31 HP:0001319
11 feeding difficulties in infancy 31 HP:0008872
12 skeletal muscle atrophy 31 HP:0003202
13 hydrops fetalis 31 HP:0001789
14 nemaline bodies 31 occasional (7.5%) HP:0003798
15 polyhydramnios 31 HP:0001561
16 areflexia 31 HP:0001284
17 decreased fetal movement 31 HP:0001558
18 motor delay 31 HP:0001270
19 muscular dystrophy 31 HP:0003560
20 increased connective tissue 31 HP:0009025
21 myopathic facies 31 HP:0002058
22 external ophthalmoplegia 31 HP:0000544
23 pulmonary hypoplasia 31 HP:0002089
24 proximal muscle weakness 31 HP:0003701
25 increased variability in muscle fiber diameter 31 HP:0003557
26 axial muscle weakness 31 HP:0003327
27 difficulty running 31 HP:0009046
28 type 1 and type 2 muscle fiber minicore regions 31 HP:0003787

UMLS symptoms related to Minicore Myopathy with External Ophthalmoplegia:


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

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 with External Ophthalmoplegia 28 RYR1

Anatomical Context for Minicore Myopathy with External Ophthalmoplegia

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

38
Lung, Skeletal Muscle

Publications for Minicore Myopathy with External Ophthalmoplegia

Articles related to Minicore Myopathy with External Ophthalmoplegia:

# Title Authors Year
1
Short-chain acyl-CoA dehydrogenase deficiency: a cause of ophthalmoplegia and multicore myopathy. ( 9932958 )
1999
2
Multicore myopathy with restrictive cardiomyopathy. ( 9401528 )
1997

Variations for Minicore Myopathy with External Ophthalmoplegia

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

71
# 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 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 RYR1 NM_000540.2(RYR1): c.14545G> A (p.Val4849Ile) single nucleotide variant Pathogenic rs118192168 GRCh37 Chromosome 19, 39071043: 39071043
2 RYR1 NM_000540.2(RYR1): c.14647-1449A> G single nucleotide variant Pathogenic rs193922886 GRCh37 Chromosome 19, 39074134: 39074134
3 RYR1 NM_000540.2(RYR1): c.325C> T (p.Arg109Trp) single nucleotide variant Pathogenic/Likely pathogenic rs118192173 GRCh37 Chromosome 19, 38934252: 38934252
4 RYR1 NM_000540.2(RYR1): c.7268T> A (p.Met2423Lys) single nucleotide variant Pathogenic rs118192174 GRCh37 Chromosome 19, 38990601: 38990601
5 RYR1 NM_000540.2(RYR1): c.14365-2A> T single nucleotide variant Pathogenic rs193922870 GRCh37 Chromosome 19, 39070620: 39070620
6 RYR1 NM_000540.2(RYR1): c.10343C> T (p.Ser3448Phe) single nucleotide variant Pathogenic rs193922836 GRCh37 Chromosome 19, 39013751: 39013751
7 RYR1 NM_000540.2(RYR1): c.1739_1742dupATCA (p.His581Glnfs) duplication Pathogenic rs193922771 GRCh37 Chromosome 19, 38946339: 38946342
8 RYR1 NM_000540.2(RYR1): c.10348-6C> G single nucleotide variant Pathogenic rs193922837 GRCh37 Chromosome 19, 39013851: 39013851
9 RYR1 NM_000540.2(RYR1): c.14126C> T (p.Thr4709Met) single nucleotide variant Pathogenic/Likely pathogenic rs118192140 GRCh37 Chromosome 19, 39063944: 39063944
10 RYR1 NM_000540.2(RYR1): c.7042_7044delGAG (p.Glu2348del) deletion Pathogenic,risk factor rs121918596 GRCh38 Chromosome 19, 38499649: 38499651
11 RYR1 NM_000540.2(RYR1): c.2097_2123del27 (p.Glu699_Gly707del) deletion Pathogenic rs876661306 GRCh38 Chromosome 19, 38458222: 38458248

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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65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
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69 UMLS
70 UMLS via Orphanet
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