MMDO
MCID: MNC011
MIFTS: 32

Minicore Myopathy with External Ophthalmoplegia (MMDO)

Categories: Cancer diseases, Genetic diseases, Neuronal diseases, Rare 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 generalized muscle weakness, edema and ophthalmoplegia. An important gene associated with Minicore Myopathy with External Ophthalmoplegia is RYR1 (Ryanodine Receptor 1). Affiliated tissues include skeletal muscle and lung, 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 12.2
2 minicore myopathy, antenatal onset, with arthrogryposis 12.2
3 rigid spine muscular dystrophy 1 11.5
4 multiminicore disease 11.5
5 chudley rozdilsky syndrome 11.2
6 myopathy 10.3
7 multiple pterygium syndrome, escobar variant 10.1
8 ectodermal dysplasia 10.1
9 restrictive cardiomyopathy 10.1
10 hypertrophic cardiomyopathy 10.1

Graphical network of the top 20 diseases related to Minicore Myopathy with External Ophthalmoplegia:



Diseases related to Minicore Myopathy with External Ophthalmoplegia

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:
proximal muscle weakness
increased connective tissue
axial muscle weakness
exercise-induced myalgia
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:

59 32 (show top 50) (show all 54)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 high palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000218
2 ptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000508
3 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
4 facial palsy 59 32 Frequent (79-30%) HP:0010628
5 recurrent respiratory infections 59 32 occasional (7.5%) Occasional (29-5%) HP:0002205
6 flexion contracture 59 32 occasional (7.5%) Occasional (29-5%) HP:0001371
7 skeletal muscle atrophy 59 32 Occasional (29-5%) HP:0003202
8 edema 59 32 occasional (7.5%) Occasional (29-5%) HP:0000969
9 feeding difficulties 59 32 frequent (33%) Frequent (79-30%) HP:0011968
10 cryptorchidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000028
11 type 1 muscle fiber atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0011807
12 motor delay 59 32 frequent (33%) Frequent (79-30%) HP:0001270
13 joint laxity 59 32 occasional (7.5%) Occasional (29-5%) HP:0001388
14 nemaline bodies 59 32 occasional (7.5%) Occasional (29-5%) HP:0003798
15 type 1 muscle fiber predominance 59 32 frequent (33%) Frequent (79-30%) HP:0003803
16 narrow face 59 32 occasional (7.5%) Occasional (29-5%) HP:0000275
17 respiratory failure 59 32 occasional (7.5%) Occasional (29-5%) HP:0002878
18 polyhydramnios 59 32 occasional (7.5%) Occasional (29-5%) HP:0001561
19 proximal muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0003701
20 decreased fetal movement 59 32 frequent (33%) Frequent (79-30%) HP:0001558
21 tented upper lip vermilion 59 32 occasional (7.5%) Occasional (29-5%) HP:0010804
22 muscular dystrophy 59 32 frequent (33%) Frequent (79-30%) HP:0003560
23 increased connective tissue 59 32 frequent (33%) Frequent (79-30%) HP:0009025
24 myopathic facies 59 32 frequent (33%) Frequent (79-30%) HP:0002058
25 axial muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0003327
26 micropenis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000054
27 facial diplegia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001349
28 increased variability in muscle fiber diameter 59 32 frequent (33%) Frequent (79-30%) HP:0003557
29 generalized hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001290
30 scrotal hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000046
31 severe postnatal growth retardation 59 32 occasional (7.5%) Occasional (29-5%) HP:0008850
32 pneumonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002090
33 external ophthalmoplegia 59 32 frequent (33%) Frequent (79-30%) HP:0000544
34 difficulty running 59 32 occasional (7.5%) Occasional (29-5%) HP:0009046
35 internally nucleated skeletal muscle fibers 59 32 frequent (33%) Frequent (79-30%) HP:0031237
36 muscle fiber hypertrophy 59 32 frequent (33%) Frequent (79-30%) HP:0100293
37 shoulder girdle muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0003547
38 frog-leg posture 59 32 occasional (7.5%) Occasional (29-5%) HP:0031139
39 rectus femoris muscle atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0040191
40 tibialis atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0011399
41 sternocleidomastoid amyotrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0012036
42 muscular hypotonia 32 HP:0001252
43 muscle weakness 59 Frequent (79-30%)
44 respiratory insufficiency 32 HP:0002093
45 neonatal hypotonia 32 HP:0001319
46 feeding difficulties in infancy 32 HP:0008872
47 generalized muscle weakness 32 HP:0003324
48 hydrops fetalis 32 HP:0001789
49 functional respiratory abnormality 59 Frequent (79-30%)
50 areflexia 32 HP:0001284

UMLS symptoms related to Minicore Myopathy with External Ophthalmoplegia:


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

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
Skeletal Muscle, Lung

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 48)
# 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.5726_5727delAG (p.Glu1909Glyfs) deletion no interpretation for the single variant rs387906681 GRCh37 Chromosome 19, 38979995: 38979996
18 RYR1 NM_000540.2(RYR1): c.5726_5727delAG (p.Glu1909Glyfs) deletion no interpretation for the single variant rs387906681 GRCh38 Chromosome 19, 38489355: 38489356
19 RYR1 NM_000540.2(RYR1): c.14524G> A (p.Val4842Met) single nucleotide variant Conflicting interpretations of pathogenicity rs193922879 GRCh37 Chromosome 19, 39071022: 39071022
20 RYR1 NM_000540.2(RYR1): c.14524G> A (p.Val4842Met) single nucleotide variant Conflicting interpretations of pathogenicity rs193922879 GRCh38 Chromosome 19, 38580382: 38580382
21 RYR1 NM_000540.2(RYR1): c.11941C> T (p.His3981Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs148772854 GRCh37 Chromosome 19, 39034444: 39034444
22 RYR1 NM_000540.2(RYR1): c.11941C> T (p.His3981Tyr) single nucleotide variant Conflicting interpretations of pathogenicity rs148772854 GRCh38 Chromosome 19, 38543804: 38543804
23 RYR1 NM_000540.2(RYR1): c.9242T> C (p.Met3081Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs147012990 GRCh37 Chromosome 19, 39002893: 39002893
24 RYR1 NM_000540.2(RYR1): c.9242T> C (p.Met3081Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs147012990 GRCh38 Chromosome 19, 38512253: 38512253
25 RYR1 NM_000540.2(RYR1): c.10348-6C> G single nucleotide variant Pathogenic/Likely pathogenic rs193922837 GRCh37 Chromosome 19, 39013851: 39013851
26 RYR1 NM_000540.2(RYR1): c.10348-6C> G single nucleotide variant Pathogenic/Likely pathogenic rs193922837 GRCh38 Chromosome 19, 38523211: 38523211
27 RYR1 NM_000540.2(RYR1): c.14126C> T (p.Thr4709Met) single nucleotide variant Pathogenic/Likely pathogenic rs118192140 GRCh37 Chromosome 19, 39063944: 39063944
28 RYR1 NM_000540.2(RYR1): c.14126C> T (p.Thr4709Met) single nucleotide variant Pathogenic/Likely pathogenic rs118192140 GRCh38 Chromosome 19, 38573304: 38573304
29 RYR1 NM_000540.2(RYR1): c.7042_7044delGAG (p.Glu2348del) deletion Pathogenic,risk factor rs121918596 GRCh38 Chromosome 19, 38499649: 38499651
30 RYR1 NM_000540.2(RYR1): c.7042_7044delGAG (p.Glu2348del) deletion Pathogenic,risk factor rs121918596 GRCh37 Chromosome 19, 38990289: 38990291
31 RYR1 NM_000540.2(RYR1): c.7063C> T (p.Arg2355Trp) single nucleotide variant Pathogenic rs193922803 GRCh38 Chromosome 19, 38499670: 38499670
32 RYR1 NM_000540.2(RYR1): c.7063C> T (p.Arg2355Trp) single nucleotide variant Pathogenic rs193922803 GRCh37 Chromosome 19, 38990310: 38990310
33 RYR1 NM_001042723.1(RYR1): c.6721C> T (p.Arg2241Ter) single nucleotide variant Pathogenic rs200563280 GRCh37 Chromosome 19, 38987106: 38987106
34 RYR1 NM_001042723.1(RYR1): c.6721C> T (p.Arg2241Ter) single nucleotide variant Pathogenic rs200563280 GRCh38 Chromosome 19, 38496466: 38496466
35 RYR1 NM_000540.2(RYR1): c.2097_2123del27 (p.Glu699_Gly707del) deletion Pathogenic rs876661306 GRCh38 Chromosome 19, 38458222: 38458248
36 RYR1 NM_000540.2(RYR1): c.2097_2123del27 (p.Glu699_Gly707del) deletion Pathogenic rs876661306 GRCh37 Chromosome 19, 38948862: 38948888
37 RYR1 NM_000540.2(RYR1): c.2654G> A (p.Arg885His) single nucleotide variant Conflicting interpretations of pathogenicity rs370634440 GRCh38 Chromosome 19, 38463499: 38463499
38 RYR1 NM_000540.2(RYR1): c.2654G> A (p.Arg885His) single nucleotide variant Conflicting interpretations of pathogenicity rs370634440 GRCh37 Chromosome 19, 38954139: 38954139
39 RYR1 NM_000540.2(RYR1): c.2383C> T (p.Arg795Cys) single nucleotide variant Uncertain significance rs547608972 GRCh38 Chromosome 19, 38460397: 38460397
40 RYR1 NM_000540.2(RYR1): c.2383C> T (p.Arg795Cys) single nucleotide variant Uncertain significance rs547608972 GRCh37 Chromosome 19, 38951037: 38951037
41 RYR1 NM_001042723.1(RYR1): c.5136_5138del (p.Leu1714del) deletion Uncertain significance GRCh37 Chromosome 19, 38976431: 38976433
42 RYR1 NM_001042723.1(RYR1): c.5136_5138del (p.Leu1714del) deletion Uncertain significance GRCh38 Chromosome 19, 38485791: 38485793
43 RYR1 NM_000540.2(RYR1): c.11687A> T (p.Asn3896Ile) single nucleotide variant Uncertain significance GRCh38 Chromosome 19, 38537958: 38537958
44 RYR1 NM_000540.2(RYR1): c.11687A> T (p.Asn3896Ile) single nucleotide variant Uncertain significance GRCh37 Chromosome 19, 39028598: 39028598
45 RYR1 NM_000540.2(RYR1): c.7093G> A (p.Gly2365Arg) single nucleotide variant Uncertain significance rs761224660 GRCh37 Chromosome 19, 38990340: 38990340
46 RYR1 NM_000540.2(RYR1): c.7093G> A (p.Gly2365Arg) single nucleotide variant Uncertain significance rs761224660 GRCh38 Chromosome 19, 38499700: 38499700
47 RYR1 NM_000540.2(RYR1): c.7215delC (p.Phe2406Leufs) deletion Pathogenic GRCh37 Chromosome 19, 38990547: 38990548
48 RYR1 NM_000540.2(RYR1): c.7215delC (p.Phe2406Leufs) deletion Pathogenic GRCh38 Chromosome 19, 38499908: 38499908

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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