MMDO
MCID: MNC011
MIFTS: 37

Minicore Myopathy with External Ophthalmoplegia (MMDO)

Categories: Cancer diseases, Genetic diseases, Muscle 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 20 73 29 13 6 71
Multiminicore Disease with External Ophthalmoplegia 57 20 73
Multicore Myopathy with External Ophthalmoplegia 20 73
Multiminicore Myopathy Multicore Myopathy with External Ophthalmoplegia 57
Congenital Multicore Myopathy with External Ophthalmoplegia 58
Myopathy, Minicore, External Ophthalmoplegia 39
Multicore Myopathy 57
Minicore Myopathy 57
Mmdo 73

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
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:
Inheritance autosomal recessive inheritance
Onset and clinical course neonatal onset


Classifications:

Orphanet: 58  
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) (Updated 05-Mar-2021)

MalaCards based summary : Minicore Myopathy with External Ophthalmoplegia, also known as multiminicore disease with external ophthalmoplegia, is related to multiminicore disease and rigid spine muscular dystrophy 1, and has symptoms including ophthalmoplegia, generalized muscle weakness and edema. 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 type 1 muscle fiber atrophy and motor delay

UniProtKB/Swiss-Prot : 73 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

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

Human phenotypes related to Minicore Myopathy with External Ophthalmoplegia:

58 31 (show top 50) (show all 54)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 type 1 muscle fiber atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0011807
2 motor delay 58 31 frequent (33%) Frequent (79-30%) HP:0001270
3 type 1 muscle fiber predominance 58 31 frequent (33%) Frequent (79-30%) HP:0003803
4 decreased fetal movement 58 31 frequent (33%) Frequent (79-30%) HP:0001558
5 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
6 muscular dystrophy 58 31 frequent (33%) Frequent (79-30%) HP:0003560
7 external ophthalmoplegia 58 31 frequent (33%) Frequent (79-30%) HP:0000544
8 generalized hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001290
9 proximal muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003701
10 increased variability in muscle fiber diameter 58 31 frequent (33%) Frequent (79-30%) HP:0003557
11 axial muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003327
12 increased connective tissue 58 31 frequent (33%) Frequent (79-30%) HP:0009025
13 myopathic facies 58 31 frequent (33%) Frequent (79-30%) HP:0002058
14 internally nucleated skeletal muscle fibers 58 31 frequent (33%) Frequent (79-30%) HP:0031237
15 muscle fiber hypertrophy 58 31 frequent (33%) Frequent (79-30%) HP:0100293
16 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
17 ptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000508
18 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
19 recurrent respiratory infections 58 31 occasional (7.5%) Occasional (29-5%) HP:0002205
20 flexion contracture 58 31 occasional (7.5%) Occasional (29-5%) HP:0001371
21 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
22 joint laxity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001388
23 nemaline bodies 58 31 occasional (7.5%) Occasional (29-5%) HP:0003798
24 rectus femoris muscle atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0040191
25 narrow face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000275
26 micropenis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000054
27 polyhydramnios 58 31 occasional (7.5%) Occasional (29-5%) HP:0001561
28 tented upper lip vermilion 58 31 occasional (7.5%) Occasional (29-5%) HP:0010804
29 respiratory failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0002878
30 scrotal hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000046
31 severe postnatal growth retardation 58 31 occasional (7.5%) Occasional (29-5%) HP:0008850
32 pneumonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002090
33 edema 58 31 occasional (7.5%) Occasional (29-5%) HP:0000969
34 shoulder girdle muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003547
35 facial diplegia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001349
36 difficulty running 58 31 occasional (7.5%) Occasional (29-5%) HP:0009046
37 frog-leg posture 58 31 occasional (7.5%) Occasional (29-5%) HP:0031139
38 tibialis atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0011399
39 sternocleidomastoid amyotrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0012036
40 facial palsy 58 31 Frequent (79-30%) HP:0010628
41 skeletal muscle atrophy 58 31 Occasional (29-5%) HP:0003202
42 muscle weakness 58 Frequent (79-30%)
43 respiratory insufficiency 31 HP:0002093
44 neonatal hypotonia 31 HP:0001319
45 feeding difficulties in infancy 31 HP:0008872
46 hydrops fetalis 31 HP:0001789
47 areflexia 31 HP:0001284
48 pulmonary hypoplasia 31 HP:0002089
49 generalized muscle weakness 31 HP:0003324
50 abnormal skeletal muscle morphology 58 Frequent (79-30%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Skeletal Spine:
scoliosis

Respiratory:
respiratory insufficiency
frequent respiratory infections
lung hypoplasia
respiratory impairment

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

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

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
hydrops

Muscle Soft Tissue:
proximal muscle weakness
axial muscle weakness
exercise-induced myalgia
increased connective tissue
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 (Updated 05-Mar-2021)

UMLS symptoms related to Minicore Myopathy with External Ophthalmoplegia:


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

Drugs & Therapeutics for Minicore Myopathy with External Ophthalmoplegia

Search Clinical Trials , 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 29 RYR1

Anatomical Context for Minicore Myopathy with External Ophthalmoplegia

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

40
Skeletal Muscle, Lung

Publications for Minicore Myopathy with External Ophthalmoplegia

Articles related to Minicore Myopathy with External Ophthalmoplegia:

(show all 22)
# Title Authors PMID Year
1
Germline mutations in RYR1 are associated with foetal akinesia deformation sequence/lethal multiple pterygium syndrome. 57 6
25476234 2014
2
RYR1 mutations are a common cause of congenital myopathies with central nuclei. 57 6
20839240 2010
3
Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores. 6 57
18253926 2008
4
Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene. 6 57
16380615 2005
5
A homozygous splicing mutation causing a depletion of skeletal muscle RYR1 is associated with multi-minicore disease congenital myopathy with ophthalmoplegia. 57 6
12719381 2003
6
Familial multicore disease with focal loss of cross-striations and ophthalmoplegia. 57 6
7299413 1981
7
RyR1 deficiency in congenital myopathies disrupts excitation-contraction coupling. 57
23553787 2013
8
Recessive RYR1 mutations in a patient with severe congenital nemaline myopathy with ophthalomoplegia identified through massively parallel sequencing. 57
22407809 2012
9
Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. 57
20583297 2010
10
First genomic rearrangement of the RYR1 gene associated with an atypical presentation of lethal neonatal hypotonia. 57
19734047 2009
11
Central core disease due to recessive mutations in RYR1 gene: is it more common than described? 6
17226826 2007
12
Centronuclear myopathy due to a de novo dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene. 57
17376685 2007
13
Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores. 6
12136074 2002
14
80th ENMC International Workshop on Multi-Minicore Disease: 1st International MmD Workshop. 12-13th May, 2000, Soestduinen, The Netherlands. 57
11731287 2002
15
Multi-minicore disease--searching for boundaries: phenotype analysis of 38 cases. 57
11079538 2000
16
Minicore myopathy in children: a clinical and histopathological study of 19 cases. 57
10838253 2000
17
Short-chain acyl-CoA dehydrogenase deficiency: a cause of ophthalmoplegia and multicore myopathy. 57
9932958 1999
18
Common origin of rods, cores, miniature cores, and focal loss of cross-striations. 57
687182 1978
19
Familial focal loss of cross striations. 57
72134 1977
20
Multicore disease. A recently recognized congenital myopathy associated with multifocal degeneration of muscle fibers. 57
5115748 1971
21
New Compound Heterozygous Splice Site Mutations of the Skeletal Muscle Ryanodine Receptor (RYR1) Gene Manifest Fetal Akinesia: A Linkage with Congenital Myopathies. 61
32655342 2020
22
Homozygous/compound heterozygote RYR1 gene variants: Expanding the clinical spectrum. 61
30652412 2019

Variations for Minicore Myopathy with External Ophthalmoplegia

ClinVar genetic disease variations for Minicore Myopathy with External Ophthalmoplegia:

6 (show top 50) (show all 467)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RYR1 NM_000540.3(RYR1):c.14524G>A (p.Val4842Met) SNV Pathogenic 65396 rs193922879 19:39071022-39071022 19:38580382-38580382
2 RYR1 NM_000540.2(RYR1):c.2097_2123del (p.Glu699_Gly707del) Deletion Pathogenic 190957 rs876661306 19:38948856-38948882 19:38458216-38458242
3 RYR1 NM_001042723.2(RYR1):c.7039_7041GAG[1] (p.Glu2348del) Microsatellite Pathogenic 133180 rs121918596 19:38990285-38990287 19:38499645-38499647
4 RYR1 NM_000540.2(RYR1):c.14126C>T (p.Thr4709Met) SNV Pathogenic 65996 rs118192140 19:39063944-39063944 19:38573304-38573304
5 RYR1 NM_001042723.2(RYR1):c.1739_1742dup (p.His581fs) Duplication Pathogenic 12994 rs193922771 19:38946337-38946338 19:38455697-38455698
6 RYR1 NM_000540.2(RYR1):c.10343C>T (p.Ser3448Phe) SNV Pathogenic 12991 rs193922836 19:39013751-39013751 19:38523111-38523111
7 RYR1 NM_000540.2(RYR1):c.14365-2A>T SNV Pathogenic 12990 rs193922870 19:39070620-39070620 19:38579980-38579980
8 RYR1 NM_000540.2(RYR1):c.7268T>A (p.Met2423Lys) SNV Pathogenic 12989 rs118192174 19:38990601-38990601 19:38499961-38499961
9 RYR1 NM_000540.3(RYR1):c.325C>T SNV Pathogenic 12988 rs118192173 19:38934252-38934252 19:38443612-38443612
10 RYR1 NM_000540.2(RYR1):c.14647-1449A>G SNV Pathogenic 12987 rs193922886 19:39074134-39074134 19:38583494-38583494
11 RYR1 NM_000540.3(RYR1):c.14545G>A (p.Val4849Ile) SNV Pathogenic 12984 rs118192168 19:39071043-39071043 19:38580403-38580403
12 RYR1 NM_000540.3(RYR1):c.14693T>C (p.Ile4898Thr) SNV Pathogenic 12975 rs118192170 19:39075629-39075629 19:38584989-38584989
13 RYR1 NM_000540.3(RYR1):c.6502G>A (p.Val2168Met) SNV Pathogenic 12976 rs118192176 19:38985219-38985219 19:38494579-38494579
14 RYR1 NM_000540.3(RYR1):c.7063C>T (p.Arg2355Trp) SNV Pathogenic 133183 rs193922803 19:38990310-38990310 19:38499670-38499670
15 RYR1 NM_000540.2(RYR1):c.7215del (p.Phe2406fs) Deletion Pathogenic 561102 rs1568501473 19:38990548-38990548 19:38499908-38499908
16 RYR1 NM_000540.3(RYR1):c.7063C>T (p.Arg2355Trp) SNV Pathogenic 133183 rs193922803 19:38990310-38990310 19:38499670-38499670
17 RYR1 NM_000540.2(RYR1):c.10347+1G>A SNV Pathogenic 224998 rs111436401 19:39013756-39013756 19:38523116-38523116
18 RYR1 NM_000540.2(RYR1):c.10348-6C>G SNV Pathogenic 132994 rs193922837 19:39013851-39013851 19:38523211-38523211
19 RYR1 NM_000540.2(RYR1):c.11763C>A (p.Tyr3921Ter) SNV Pathogenic 161361 rs377178986 19:39034060-39034060 19:38543420-38543420
20 RYR1 NM_000540.2(RYR1):c.2505del (p.Pro836fs) Deletion Pathogenic 212099 rs797045932 19:38951155-38951155 19:38460515-38460515
21 RYR1 NM_000540.2(RYR1):c.6664-2A>G SNV Pathogenic 544381 rs1346257891 19:38987047-38987047 19:38496407-38496407
22 RYR1 NM_000540.3(RYR1):c.7330C>T (p.Gln2444Ter) SNV Pathogenic 870624 19:38991252-38991252 19:38500612-38500612
23 RYR1 NM_000540.3(RYR1):c.6721C>T (p.Arg2241Ter) SNV Pathogenic 159856 rs200563280 19:38987106-38987106 19:38496466-38496466
24 RYR1 NM_001042723.2(RYR1):c.5724_5725AG[1] (p.Glu1909fs) Microsatellite Pathogenic 29876 rs387906681 19:38979993-38979994 19:38489353-38489354
25 RYR1 NM_000540.2(RYR1):c.10347+1G>A SNV Pathogenic 224998 rs111436401 19:39013756-39013756 19:38523116-38523116
26 RYR1 NM_000540.2(RYR1):c.4496_4497del (p.Phe1499fs) Deletion Pathogenic 617750 rs1568476203 19:38969115-38969116 19:38478475-38478476
27 RYR1 NM_000540.3(RYR1):c.685T>C (p.Cys229Arg) SNV Likely pathogenic 807480 rs1600649879 19:38937165-38937165 19:38446525-38446525
28 RYR1 NM_000540.2(RYR1):c.9716T>A (p.Met3239Lys) SNV Likely pathogenic 617753 rs371027185 19:39008029-39008029 19:38517389-38517389
29 RYR1 NM_000540.3(RYR1):c.11314C>T SNV Likely pathogenic 478159 rs763112609 19:39025414-39025414 19:38534774-38534774
30 RYR1 NM_000540.3(RYR1):c.14701G>A (p.Glu4901Lys) SNV Likely pathogenic 973242 19:39075637-39075637 19:38584997-38584997
31 RYR1 NM_000540.3(RYR1):c.3880G>T (p.Val1294Phe) SNV Likely pathogenic 870619 19:38964131-38964131 19:38473491-38473491
32 RYR1 NM_000540.3(RYR1):c.4454G>A (p.Ser1485Asn) SNV Likely pathogenic 870620 19:38968510-38968510 19:38477870-38477870
33 RYR1 NM_000540.3(RYR1):c.4715T>C (p.Met1572Thr) SNV Likely pathogenic 870621 19:38973937-38973937 19:38483297-38483297
34 RYR1 NM_000540.3(RYR1):c.658C>T (p.Arg220Cys) SNV Likely pathogenic 870622 19:38937138-38937138 19:38446498-38446498
35 RYR1 NM_000540.2(RYR1):c.14126C>T (p.Thr4709Met) SNV Likely pathogenic 65996 rs118192140 19:39063944-39063944 19:38573304-38573304
36 RYR1 NM_000540.2(RYR1):c.11687A>T (p.Asn3896Ile) SNV Uncertain significance 548498 rs1555793251 19:39028598-39028598 19:38537958-38537958
37 RYR1 NM_001042723.1(RYR1):c.5140_5142del (p.Leu1714del) Microsatellite Uncertain significance 548508 rs1438501767 19:38976431-38976433 19:38485791-38485793
38 RYR1 NM_001042723.2(RYR1):c.2654G>A (p.Arg885His) SNV Uncertain significance 212100 rs370634440 19:38954139-38954139 19:38463499-38463499
39 RYR1 NM_001042723.2(RYR1):c.2383C>T (p.Arg795Cys) SNV Uncertain significance 478212 rs547608972 19:38951037-38951037 19:38460397-38460397
40 RYR1 NM_000540.3(RYR1):c.7093G>A SNV Uncertain significance 561101 rs761224660 19:38990340-38990340 19:38499700-38499700
41 RYR1 NM_000540.2(RYR1):c.7876C>T (p.Leu2626=) SNV Uncertain significance 256565 rs145446438 19:38993560-38993560 19:38502920-38502920
42 RYR1 NM_000540.2(RYR1):c.3257G>A (p.Arg1086His) SNV Uncertain significance 572240 rs764009626 19:38958328-38958328 19:38467688-38467688
43 RYR1 NM_000540.3(RYR1):c.3319G>A (p.Glu1107Lys) SNV Uncertain significance 890998 19:38958390-38958390 19:38467750-38467750
44 RYR1 NM_000540.3(RYR1):c.8377C>T (p.Pro2793Ser) SNV Uncertain significance 890999 19:38996015-38996015 19:38505375-38505375
45 RYR1 NM_000540.3(RYR1):c.8662C>T (p.Arg2888Trp) SNV Uncertain significance 891067 19:38997156-38997156 19:38506516-38506516
46 RYR1 NM_000540.3(RYR1):c.4056G>A (p.Ala1352=) SNV Uncertain significance 758642 rs915321867 19:38964307-38964307 19:38473667-38473667
47 RYR1 NM_000540.2(RYR1):c.9122+8G>A SNV Uncertain significance 544504 rs772116480 19:39001429-39001429 19:38510789-38510789
48 RYR1 NM_000540.2(RYR1):c.9513T>C (p.Ser3171=) SNV Uncertain significance 590632 rs1568524980 19:39005706-39005706 19:38515066-38515066
49 RYR1 NM_000540.3(RYR1):c.9554+13A>T SNV Uncertain significance 891194 19:39005760-39005760 19:38515120-38515120
50 RYR1 NM_000540.3(RYR1):c.9555-14G>A SNV Uncertain significance 891195 19:39006713-39006713 19:38516073-38516073

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

73
# 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

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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