MCID: MYS074
MIFTS: 23

Myasthenic Syndrome, Congenital, 12

Categories: Genetic diseases, Neuronal diseases, Eye diseases, Rare diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 12

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 12:

Name: Myasthenic Syndrome, Congenital, 12 57 75
Congenital Myasthenic Syndrome 12 12 29 6
Cms12 57 12 75
Myasthenic Syndrome, Congenital, with Tubular Aggregates 1 57 73
Myasthenia, Congenital, with Tubular Aggregates 1 75 13
Cmsta1 57 75
Myasthenic Syndrome, Congenital, with Tubular Aggregates 1; Cmsta1 57
Myasthenic Syndrome, Congenital, with Tubular Aggregates, 1 75
Myasthenia, Congenital, 12, with Tubular Aggregates 57
Congenital Myasthenia 12 with Tubular Aggregates 12
Limb-Girdle Myasthenia with Tubular Aggregates 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in first decade
favorable response to acetylcholinesterase inhibitors
distinct disorder from acquired limb-girdle myasthenia and congenital limb-girdle myasthenia


HPO:

32
myasthenic syndrome, congenital, 12:
Onset and clinical course juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 12

UniProtKB/Swiss-Prot : 75 Myasthenic syndrome, congenital, 12: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre- synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. CMS12 is characterized by onset of proximal muscle weakness in the first decade. Individuals with this condition have a recognizable pattern of weakness of shoulder and pelvic girdle muscles, and sparing of ocular or facial muscles. EMG classically shows a decremental response to repeated nerve stimulation, a sign of neuromuscular junction dysfunction. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors.

MalaCards based summary : Myasthenic Syndrome, Congenital, 12, is also known as congenital myasthenic syndrome 12, and has symptoms including muscle cramp, waddling gait and facial paresis. An important gene associated with Myasthenic Syndrome, Congenital, 12 is GFPT1 (Glutamine--Fructose-6-Phosphate Transaminase 1). Related phenotypes are ptosis and facial palsy

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of onset of proximal muscle weakness in the first decade that generally responds well to acetylcholinesterase inhibitor treatment that has material basis in homozygous or compound heterozygous mutation in the GFPT1 gene on chromosome 2p13.

OMIM : 57 Congenital myasthenic syndrome-12 is an autosomal recessive neuromuscular disorder characterized by onset of proximal muscle weakness in the first decade. EMG classically shows a decremental response to repeated nerve stimulation. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors (summary by Senderek et al., 2011). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (610542)

Related Diseases for Myasthenic Syndrome, Congenital, 12

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 12

Symptoms via clinical synopsis from OMIM:

57
Neurologic Peripheral Nervous System:
muscle cramps
waddling gait
easy fatigability
gowers sign
proximal muscle weakness due to defect at the neuromuscular junction
more
Head And Neck Eyes:
absence of ophthalmoparesis
ptosis (less common)

Head And Neck Face:
facial weakness

Respiratory:
respiratory muscle weakness may occur

Head And Neck Neck:
neck muscle weakness

Laboratory Abnormalities:
mildly increased serum creatine kinase

Immunology:
absence of acetylcholine receptor (achr) autoantibodies

Muscle Soft Tissue:
muscle biopsy shows 60-80-nm tubular aggregates arranged in hexagonal arrays in type 2 fibers


Clinical features from OMIM:

610542

Human phenotypes related to Myasthenic Syndrome, Congenital, 12:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 ptosis 32 HP:0000508
2 facial palsy 32 HP:0010628
3 ophthalmoparesis 32 HP:0000597
4 muscle cramps 32 HP:0003394
5 mildly elevated creatine phosphokinase 32 HP:0008180
6 motor delay 32 occasional (7.5%) HP:0001270
7 neck muscle weakness 32 HP:0000467
8 fatigable weakness 32 HP:0003473
9 proximal amyotrophy 32 HP:0007126
10 waddling gait 32 HP:0002515
11 easy fatigability 32 HP:0003388
12 gowers sign 32 HP:0003391
13 emg 32 HP:0003403

UMLS symptoms related to Myasthenic Syndrome, Congenital, 12:


muscle cramp, waddling gait, facial paresis

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 12

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 12

Genetic Tests for Myasthenic Syndrome, Congenital, 12

Genetic tests related to Myasthenic Syndrome, Congenital, 12:

# Genetic test Affiliating Genes
1 Congenital Myasthenic Syndrome 12 29 GFPT1

Anatomical Context for Myasthenic Syndrome, Congenital, 12

Publications for Myasthenic Syndrome, Congenital, 12

Articles related to Myasthenic Syndrome, Congenital, 12:

# Title Authors Year
1
Limb-girdle myasthenia with tubular aggregates associated with novel GFPT1 mutations. ( 22987706 )
2012

Variations for Myasthenic Syndrome, Congenital, 12

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 12:

75 (show all 13)
# Symbol AA change Variation ID SNP ID
1 GFPT1 p.Thr15Ala VAR_065339 rs387906638
2 GFPT1 p.Thr15Met VAR_065340 rs751097758
3 GFPT1 p.Asp43Val VAR_065341
4 GFPT1 p.Arg111Cys VAR_065342 rs201322234
5 GFPT1 p.Ile121Thr VAR_065343 rs753866967
6 GFPT1 p.Val199Phe VAR_065344
7 GFPT1 p.Asp366Tyr VAR_065345
8 GFPT1 p.Arg403His VAR_065346
9 GFPT1 p.Arg452His VAR_065347
10 GFPT1 p.Met509Thr VAR_065348
11 GFPT1 p.Met510Thr VAR_065349
12 GFPT1 p.Arg514Trp VAR_065350
13 GFPT1 p.Arg530Trp VAR_065351 rs1024585946Myasthenic

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 12:

6
(show top 50) (show all 58)
# Gene Variation Type Significance SNP ID Assembly Location
1 GFPT1 NM_001244710.1(GFPT1): c.331C> T (p.Arg111Cys) single nucleotide variant Pathogenic rs201322234 GRCh37 Chromosome 2, 69590695: 69590695
2 GFPT1 NM_001244710.1(GFPT1): c.331C> T (p.Arg111Cys) single nucleotide variant Pathogenic rs201322234 GRCh38 Chromosome 2, 69363563: 69363563
3 GFPT1 GFPT1, 1-BP INS, 222A insertion Pathogenic
4 GFPT1 GFPT1, TRP240TER single nucleotide variant Pathogenic
5 GFPT1 GFPT1, ASP348TYR single nucleotide variant Pathogenic
6 GFPT1 NM_001244710.1(GFPT1): c.43A> G (p.Thr15Ala) single nucleotide variant Pathogenic rs387906638 GRCh37 Chromosome 2, 69601210: 69601210
7 GFPT1 NM_001244710.1(GFPT1): c.43A> G (p.Thr15Ala) single nucleotide variant Pathogenic rs387906638 GRCh38 Chromosome 2, 69374078: 69374078
8 GFPT1 GFPT1, 1-BP DEL, NT621 deletion Pathogenic
9 GFPT1 NM_002056.3(GFPT1): c.*22C> A single nucleotide variant Uncertain significance rs199678034 GRCh37 Chromosome 2, 69553299: 69553299
10 GFPT1 NM_002056.3(GFPT1): c.*22C> A single nucleotide variant Uncertain significance rs199678034 GRCh38 Chromosome 2, 69326167: 69326167
11 GFPT1 NM_001244710.1(GFPT1): c.408+7A> T single nucleotide variant Benign/Likely benign rs112682152 GRCh38 Chromosome 2, 69359261: 69359261
12 GFPT1 NM_001244710.1(GFPT1): c.408+7A> T single nucleotide variant Benign/Likely benign rs112682152 GRCh37 Chromosome 2, 69586393: 69586393
13 GFPT1 NM_002056.3(GFPT1): c.1828G> A (p.Val610Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs190072721 GRCh38 Chromosome 2, 69328282: 69328282
14 GFPT1 NM_002056.3(GFPT1): c.1828G> A (p.Val610Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs190072721 GRCh37 Chromosome 2, 69555414: 69555414
15 GFPT1 NM_002056.3(GFPT1): c.549T> C (p.Gly183=) single nucleotide variant Benign/Likely benign rs144566433 GRCh38 Chromosome 2, 69356552: 69356552
16 GFPT1 NM_002056.3(GFPT1): c.549T> C (p.Gly183=) single nucleotide variant Benign/Likely benign rs144566433 GRCh37 Chromosome 2, 69583684: 69583684
17 GFPT1 NM_002056.3(GFPT1): c.1871A> T (p.Asp624Val) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 69554176: 69554176
18 GFPT1 NM_002056.3(GFPT1): c.1871A> T (p.Asp624Val) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 69327044: 69327044
19 GFPT1 NM_002056.3(GFPT1): c.987A> T (p.Ile329=) single nucleotide variant Likely benign rs772941507 GRCh37 Chromosome 2, 69573100: 69573100
20 GFPT1 NM_002056.3(GFPT1): c.987A> T (p.Ile329=) single nucleotide variant Likely benign rs772941507 GRCh38 Chromosome 2, 69345968: 69345968
21 GFPT1 NM_002056.3(GFPT1): c.981G> A (p.Lys327=) single nucleotide variant Likely benign rs373488949 GRCh37 Chromosome 2, 69573106: 69573106
22 GFPT1 NM_002056.3(GFPT1): c.981G> A (p.Lys327=) single nucleotide variant Likely benign rs373488949 GRCh38 Chromosome 2, 69345974: 69345974
23 GFPT1 NM_002056.3(GFPT1): c.29A> G (p.Tyr10Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 69374092: 69374092
24 GFPT1 NM_002056.3(GFPT1): c.29A> G (p.Tyr10Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 69601224: 69601224
25 GFPT1 NM_002056.3(GFPT1): c.1255T> A (p.Phe419Ile) single nucleotide variant Uncertain significance rs766450555 GRCh37 Chromosome 2, 69565592: 69565592
26 GFPT1 NM_002056.3(GFPT1): c.1255T> A (p.Phe419Ile) single nucleotide variant Uncertain significance rs766450555 GRCh38 Chromosome 2, 69338460: 69338460
27 GFPT1 NM_002056.3(GFPT1): c.816C> T (p.Arg272=) single nucleotide variant Likely benign rs754486756 GRCh37 Chromosome 2, 69575442: 69575442
28 GFPT1 NM_002056.3(GFPT1): c.816C> T (p.Arg272=) single nucleotide variant Likely benign rs754486756 GRCh38 Chromosome 2, 69348310: 69348310
29 GFPT1 NM_002056.3(GFPT1): c.1507C> T (p.Arg503Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 69329720: 69329720
30 GFPT1 NM_002056.3(GFPT1): c.1507C> T (p.Arg503Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 69556852: 69556852
31 GFPT1 NM_002056.3(GFPT1): c.1480G> A (p.Asp494Asn) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 69556879: 69556879
32 GFPT1 NM_002056.3(GFPT1): c.1480G> A (p.Asp494Asn) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 69329747: 69329747
33 GFPT1 NM_002056.3(GFPT1): c.1129A> G (p.Ser377Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 69342172: 69342172
34 GFPT1 NM_002056.3(GFPT1): c.1129A> G (p.Ser377Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 69569304: 69569304
35 GFPT1 NM_002056.3(GFPT1): c.956-10A> G single nucleotide variant Likely benign rs753072061 GRCh37 Chromosome 2, 69573141: 69573141
36 GFPT1 NM_002056.3(GFPT1): c.956-10A> G single nucleotide variant Likely benign rs753072061 GRCh38 Chromosome 2, 69346009: 69346009
37 GFPT1 NM_002056.3(GFPT1): c.606-3C> T single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 69354571: 69354571
38 GFPT1 NM_002056.3(GFPT1): c.606-3C> T single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 69581703: 69581703
39 GFPT1 NM_002056.3(GFPT1): c.224-10T> C single nucleotide variant Benign rs777508704 GRCh38 Chromosome 2, 69363680: 69363680
40 GFPT1 NM_002056.3(GFPT1): c.224-10T> C single nucleotide variant Benign rs777508704 GRCh37 Chromosome 2, 69590812: 69590812
41 GFPT1 NM_002056.3(GFPT1): c.2001+3A> G single nucleotide variant Uncertain significance rs937857366 GRCh38 Chromosome 2, 69326911: 69326911
42 GFPT1 NM_002056.3(GFPT1): c.2001+3A> G single nucleotide variant Uncertain significance rs937857366 GRCh37 Chromosome 2, 69554043: 69554043
43 GFPT1 NM_002056.3(GFPT1): c.1908G> C (p.Lys636Asn) single nucleotide variant Uncertain significance rs368208403 GRCh37 Chromosome 2, 69554139: 69554139
44 GFPT1 NM_002056.3(GFPT1): c.1908G> C (p.Lys636Asn) single nucleotide variant Uncertain significance rs368208403 GRCh38 Chromosome 2, 69327007: 69327007
45 GFPT1 NM_002056.3(GFPT1): c.1133A> T (p.Tyr378Phe) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 69569300: 69569300
46 GFPT1 NM_002056.3(GFPT1): c.1133A> T (p.Tyr378Phe) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 69342168: 69342168
47 GFPT1 NM_002056.3(GFPT1): c.1124G> C (p.Gly375Ala) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 69569309: 69569309
48 GFPT1 NM_002056.3(GFPT1): c.1124G> C (p.Gly375Ala) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 69342177: 69342177
49 GFPT1 NM_002056.3(GFPT1): c.791+6C> T single nucleotide variant Uncertain significance rs767647134 GRCh37 Chromosome 2, 69577204: 69577204
50 GFPT1 NM_002056.3(GFPT1): c.791+6C> T single nucleotide variant Uncertain significance rs767647134 GRCh38 Chromosome 2, 69350072: 69350072

Expression for Myasthenic Syndrome, Congenital, 12

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 12.

Pathways for Myasthenic Syndrome, Congenital, 12

GO Terms for Myasthenic Syndrome, Congenital, 12

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