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Congenital myasthenic syndrome 13(CMS13)

MedGen UID:
766559
•Concept ID:
C3553645
•
Disease or Syndrome
Synonyms: CMS13; Myasthenic syndrome, congenital, 13, with tubular aggregates; Myasthenic syndrome, congenital, with tubular aggregates 2
 
Gene (location): DPAGT1 (11q23.3)
 
Monarch Initiative: MONDO:0013883
OMIM®: 614750

Definition

Congenital myasthenic syndrome-13 (CMS13) 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 Belaya et al., 2012). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). [from OMIM]

Clinical features

From HPO
Fatigable weakness
MedGen UID:
451076
•Concept ID:
C0947912
•
Disease or Syndrome
A type of weakness that occurs after a muscle group is used and lessens if the muscle group has some rest. That is, there is diminution of strength with repetitive muscle actions.
See: Feature record | Search on this feature
Motor delay
MedGen UID:
381392
•Concept ID:
C1854301
•
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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Hypotonia
MedGen UID:
10133
•Concept ID:
C0026827
•
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
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Scoliosis
MedGen UID:
11348
•Concept ID:
C0036439
•
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
See: Feature record | Search on this feature
Proximal muscle weakness
MedGen UID:
113169
•Concept ID:
C0221629
•
Finding
A lack of strength of the proximal muscles.
See: Feature record | Search on this feature
Muscle fiber tubular inclusions
MedGen UID:
866677
•Concept ID:
C4021024
•
Anatomical Abnormality
Unusual regions of densely packed membranous tubules known as tubular aggregates which present as membranous inclusions, derived from membranes of sarcoplasmic reticulum and mitochondria, containing miscellaneous proteins with a variety of enzymatic activities.
See: Feature record | Search on this feature
Increased jitter at single fiber EMG
MedGen UID:
866698
•Concept ID:
C4021045
•
Finding
The variation in the time interval between the two action potentials of the same motor unit is called jitter. This term therefore applies to increased variability in the interval between successive action potentials of the same motor unit, which is measured by electromyography (EMG).
See: Feature record | Search on this feature
EMG: decremental response of compound muscle action potential to repetitive nerve stimulation
MedGen UID:
892749
•Concept ID:
C4021728
•
Finding
A compound muscle action potential (CMAP) is a type of electromyography (EMG). CMAP refers to a group of almost simultaneous action potentials from several muscle fibers in the same area evoked by stimulation of the supplying motor nerve and are recorded as one multipeaked summated action potential. This abnormality refers to a greater than normal decrease in the amplitude during the course of the investigation.
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Ptosis
MedGen UID:
2287
•Concept ID:
C0005745
•
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
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Professional guidelines

PubMed

Broad phenotypic spectrum and genotype-phenotype correlations in GMPPB-related dystroglycanopathies: an Italian cross-sectional study.
Astrea G, Romano A, Angelini C, Antozzi CG, Barresi R, Battini R, Battisti C, Bertini E, Bruno C, Cassandrini D, Fanin M, Fattori F, Fiorillo C, Guerrini R, Maggi L, Mercuri E, Morani F, Mora M, Moro F, Pezzini I, Picillo E, Pinelli M, Politano L, Rubegni A, Sanseverino W, Savarese M, Striano P, Torella A, Trevisan CP, Trovato R, Zaraieva I, Muntoni F, Nigro V, D'Amico A, Santorelli FM; Italian CMD Network
Orphanet J Rare Dis 2018 Sep 26;13(1):170. doi: 10.1186/s13023-018-0863-x. PMID: 30257713Free PMC Article
Pharmacologic treatment of downstream of tyrosine kinase 7 congenital myasthenic syndrome.
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145

Recent clinical studies

Etiology

The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study.
Krenn M, Sener M, Rath J, Zulehner G, Keritam O, Wagner M, Laccone F, Iglseder S, Marte S, Baumgartner M, Eisenkölbl A, Liechtenstein C, Rudnik S, Quasthoff S, Grinzinger S, Spenger J, Wortmann SB, Löscher WN, Zimprich F, Kellersmann A, Rappold M, Bernert G, Freilinger M, Cetin H
J Neurol 2023 Feb;270(2):909-916. Epub 2022 Oct 29 doi: 10.1007/s00415-022-11440-0. PMID: 36308527Free PMC Article
Bedside and laboratory diagnostic testing in myasthenia.
Yoganathan K, Stevenson A, Tahir A, Sadler R, Radunovic A, Malek N
J Neurol 2022 Jun;269(6):3372-3384. Epub 2022 Feb 10 doi: 10.1007/s00415-022-10986-3. PMID: 35142871Free PMC Article
Congenital myasthenic syndrome in China: genetic and myopathological characterization.
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Congenital myasthenic syndromes in the Thai population: Clinical findings and novel mutations.
Pattrakornkul N, Ittiwut C, Boonsimma P, Boonyapisit K, Khongkhatithum C, Sanmaneechai O, Suphapeetiporn K, Shotelersuk V
Neuromuscul Disord 2020 Oct;30(10):851-858. Epub 2020 Aug 29 doi: 10.1016/j.nmd.2020.08.362. PMID: 32978031
Pharmacologic treatment of downstream of tyrosine kinase 7 congenital myasthenic syndrome.
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145

Diagnosis

The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD).
Allen NM, O'Rahelly M, Eymard B, Chouchane M, Hahn A, Kearns G, Kim DS, Byun SY, Nguyen CE, Schara-Schmidt U, Kölbel H, Marina AD, Schneider-Gold C, Roefke K, Thieme A, Van den Bergh P, Avalos G, Álvarez-Velasco R, Natera-de Benito D, Cheng MHM, Chan WK, Wan HS, Thomas MA, Borch L, Lauzon J, Kornblum C, Reimann J, Mueller A, Kuntzer T, Norwood F, Ramdas S, Jacobson LW, Jie X, Fernandez-Garcia MA, Wraige E, Lim M, Lin JP, Claeys KG, Aktas S, Oskoui M, Hacohen Y, Masud A, Leite MI, Palace J, De Vivo D, Vincent A, Jungbluth H
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The clinical and molecular landscape of congenital myasthenic syndromes in Austria: a nationwide study.
Krenn M, Sener M, Rath J, Zulehner G, Keritam O, Wagner M, Laccone F, Iglseder S, Marte S, Baumgartner M, Eisenkölbl A, Liechtenstein C, Rudnik S, Quasthoff S, Grinzinger S, Spenger J, Wortmann SB, Löscher WN, Zimprich F, Kellersmann A, Rappold M, Bernert G, Freilinger M, Cetin H
J Neurol 2023 Feb;270(2):909-916. Epub 2022 Oct 29 doi: 10.1007/s00415-022-11440-0. PMID: 36308527Free PMC Article
Bedside and laboratory diagnostic testing in myasthenia.
Yoganathan K, Stevenson A, Tahir A, Sadler R, Radunovic A, Malek N
J Neurol 2022 Jun;269(6):3372-3384. Epub 2022 Feb 10 doi: 10.1007/s00415-022-10986-3. PMID: 35142871Free PMC Article
Congenital myasthenic syndrome in China: genetic and myopathological characterization.
Zhao Y, Li Y, Bian Y, Yao S, Liu P, Yu M, Zhang W, Wang Z, Yuan Y
Ann Clin Transl Neurol 2021 Apr;8(4):898-907. Epub 2021 Mar 23 doi: 10.1002/acn3.51346. PMID: 33756069Free PMC Article
Congenital myasthenic syndrome in Israel: Genetic and clinical characterization.
Aharoni S, Sadeh M, Shapira Y, Edvardson S, Daana M, Dor-Wollman T, Mimouni-Bloch A, Halevy A, Cohen R, Sagie L, Argov Z, Rabie M, Spiegel R, Chervinsky I, Orenstein N, Engel AG, Nevo Y
Neuromuscul Disord 2017 Feb;27(2):136-140. Epub 2016 Nov 24 doi: 10.1016/j.nmd.2016.11.014. PMID: 28024842Free PMC Article

Therapy

COLQ-Congenital myasthenic syndrome in an Iranian cohort: the clinical and genetics spectrum.
Hesami O, Ramezani M, Ghasemi A, Fatehi F, Okhovat AA, Ziaadini B, Kariminejad A, Nafissi S
Orphanet J Rare Dis 2024 Mar 12;19(1):113. doi: 10.1186/s13023-024-03116-x. PMID: 38475910Free PMC Article
Unexpected dislocation following accurate total hip arthroplasty caused by excessive hip joint laxity during myasthenic crisis: a case report.
Murotani Y, Kuroda Y, Goto K, Kawai T, Matsuda S
J Med Case Rep 2018 Nov 6;12(1):331. doi: 10.1186/s13256-018-1886-6. PMID: 30396362Free PMC Article
Exome sequencing detection of two untranslated GFPT1 mutations in a family with limb-girdle myasthenia.
Maselli RA, Arredondo J, Nguyen J, Lara M, Ng F, Ngo M, Pham JM, Yi Q, Stajich JM, McDonald K, Hauser MA, Wollmann RL
Clin Genet 2014 Feb;85(2):166-71. Epub 2013 Mar 11 doi: 10.1111/cge.12118. PMID: 23488891
Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes.
Müller JS, Herczegfalvi A, Vilchez JJ, Colomer J, Bachinski LL, Mihaylova V, Santos M, Schara U, Deschauer M, Shevell M, Poulin C, Dias A, Soudo A, Hietala M, Aärimaa T, Krahe R, Karcagi V, Huebner A, Beeson D, Abicht A, Lochmüller H
Brain 2007 Jun;130(Pt 6):1497-506. Epub 2007 Apr 17 doi: 10.1093/brain/awm068. PMID: 17439981
Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations.
Müller JS, Baumeister SK, Rasic VM, Krause S, Todorovic S, Kugler K, Müller-Felber W, Abicht A, Lochmüller H
Neurology 2006 Oct 10;67(7):1159-64. Epub 2006 Aug 23 doi: 10.1212/01.wnl.0000233837.79459.40. PMID: 16931511

Prognosis

A Dpagt1 Missense Variant Causes Degenerative Retinopathy without Myasthenic Syndrome in Mice.
Hyde LF, Kong Y, Zhao L, Rao SR, Wang J, Stone L, Njaa A, Collin GB, Krebs MP, Chang B, Fliesler SJ, Nishina PM, Naggert JK
Int J Mol Sci 2022 Oct 9;23(19) doi: 10.3390/ijms231912005. PMID: 36233305Free PMC Article
Congenital myasthenic syndrome in China: genetic and myopathological characterization.
Zhao Y, Li Y, Bian Y, Yao S, Liu P, Yu M, Zhang W, Wang Z, Yuan Y
Ann Clin Transl Neurol 2021 Apr;8(4):898-907. Epub 2021 Mar 23 doi: 10.1002/acn3.51346. PMID: 33756069Free PMC Article
Posterior Segment Characterization in Children With Pierson Syndrome.
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Incidence and Ocular Features of Pediatric Myasthenias.
Mansukhani SA, Bothun ED, Diehl NN, Mohney BG
Am J Ophthalmol 2019 Apr;200:242-249. Epub 2019 Jan 14 doi: 10.1016/j.ajo.2019.01.004. PMID: 30653958Free PMC Article
Splicing abnormalities in congenital myasthenic syndromes.
Ohno K, Engel AG
Acta Myol 2005 Oct;24(2):50-4. PMID: 16550914

Clinical prediction guides

Adeno-Associated Virus Type 9-Mediated Gene Therapy of Choline Acetyltransferase-Deficient Mice.
Lin CV, Thomas CAD, Huynh TL, Wei DT, Young JN, Aivazian AS, McInnes A, Xu J, Cook SE, Vazquez J, Maselli RA
Hum Gene Ther 2024 Feb;35(3-4):123-131. doi: 10.1089/hum.2023.173. PMID: 38299967
Congenital myasthenic syndrome in China: genetic and myopathological characterization.
Zhao Y, Li Y, Bian Y, Yao S, Liu P, Yu M, Zhang W, Wang Z, Yuan Y
Ann Clin Transl Neurol 2021 Apr;8(4):898-907. Epub 2021 Mar 23 doi: 10.1002/acn3.51346. PMID: 33756069Free PMC Article
Posterior Segment Characterization in Children With Pierson Syndrome.
AlTaisan A, Magliyah M, Abouammoh MA, Taskintuna I, Alzahrani Y, Chang E, Alsulaiman SM
Ophthalmic Surg Lasers Imaging Retina 2020 Nov 1;51(11):618-627. doi: 10.3928/23258160-20201104-03. PMID: 33231694
Sleep in infants with congenital myasthenic syndromes.
Caggiano S, Khirani S, Verrillo E, Barnerias C, Amaddeo A, Gitiaux C, Thierry B, Desguerre I, Cutrera R, Fauroux B
Eur J Paediatr Neurol 2017 Nov;21(6):842-851. Epub 2017 Jul 21 doi: 10.1016/j.ejpn.2017.07.010. PMID: 28755803
Pharmacologic treatment of downstream of tyrosine kinase 7 congenital myasthenic syndrome.
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145

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