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Congenital myasthenic syndrome 21(CMS21)

MedGen UID:
934621
Concept ID:
C4310654
Disease or Syndrome
Synonym: Myasthenic syndrome, congenital, 21, presynaptic
 
Gene (location): SLC18A3 (10q11.23)
 
Monarch Initiative: MONDO:0014983
OMIM®: 617239

Definition

Any congenital myasthenic syndrome in which the cause of the disease is a mutation in the SLC18A3 gene. [from MONDO]

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Exercise intolerance
MedGen UID:
603270
Concept ID:
C0424551
Finding
A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A bent (flexed) knee joint that cannot be straightened actively or passively.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Difficulty walking
MedGen UID:
86319
Concept ID:
C0311394
Finding
Reduced ability to walk (ambulate).
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
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).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Ophthalmoplegia
MedGen UID:
45205
Concept ID:
C0029089
Sign or Symptom
Paralysis of one or more extraocular muscles that are responsible for eye movements.

Professional guidelines

PubMed

Verschuuren JJ, Palace J, Murai H, Tannemaat MR, Kaminski HJ, Bril V
Lancet Neurol 2022 Feb;21(2):189-202. doi: 10.1016/S1474-4422(21)00463-4. PMID: 35065041
Kinali M, Beeson D, Pitt MC, Jungbluth H, Simonds AK, Aloysius A, Cockerill H, Davis T, Palace J, Manzur AY, Jimenez-Mallebrera C, Sewry C, Muntoni F, Robb SA
J Neuroimmunol 2008 Sep 15;201-202:6-12. Epub 2008 Aug 15 doi: 10.1016/j.jneuroim.2008.06.026. PMID: 18707767

Recent clinical studies

Etiology

Hoei-Hansen CE, Tygesen MLB, Dunø M, Vissing J, Ballegaard M, Born AP
Neuropediatrics 2021 Dec;52(6):462-468. Epub 2021 Mar 11 doi: 10.1055/s-0041-1726120. PMID: 33706403
Hamasaki Y, Hamada R, Muramatsu M, Matsumoto S, Aya K, Ishikura K, Kaneko T, Iijima K
BMC Nephrol 2020 Aug 24;21(1):363. doi: 10.1186/s12882-020-02010-5. PMID: 32838745Free PMC Article
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
Cossins J, Liu WW, Belaya K, Maxwell S, Oldridge M, Lester T, Robb S, Beeson D
Hum Mol Genet 2012 Sep 1;21(17):3765-75. Epub 2012 Jun 1 doi: 10.1093/hmg/dds198. PMID: 22661499
Kinali M, Beeson D, Pitt MC, Jungbluth H, Simonds AK, Aloysius A, Cockerill H, Davis T, Palace J, Manzur AY, Jimenez-Mallebrera C, Sewry C, Muntoni F, Robb SA
J Neuroimmunol 2008 Sep 15;201-202:6-12. Epub 2008 Aug 15 doi: 10.1016/j.jneuroim.2008.06.026. PMID: 18707767

Diagnosis

Hoei-Hansen CE, Tygesen MLB, Dunø M, Vissing J, Ballegaard M, Born AP
Neuropediatrics 2021 Dec;52(6):462-468. Epub 2021 Mar 11 doi: 10.1055/s-0041-1726120. PMID: 33706403
Caldas VM, Heise CO, Kouyoumdjian JA, Zambon AA, Silva AMS, Estephan EP, Zanoteli E
Neuromuscul Disord 2020 Nov;30(11):897-903. Epub 2020 Oct 14 doi: 10.1016/j.nmd.2020.10.002. PMID: 33121830
Hamasaki Y, Hamada R, Muramatsu M, Matsumoto S, Aya K, Ishikura K, Kaneko T, Iijima K
BMC Nephrol 2020 Aug 24;21(1):363. doi: 10.1186/s12882-020-02010-5. PMID: 32838745Free PMC Article
Milone M, Shen XM, Selcen D, Ohno K, Brengman J, Iannaccone ST, Harper CM, Engel AG
Neurology 2009 Jul 21;73(3):228-35. doi: 10.1212/WNL.0b013e3181ae7cbc. PMID: 19620612Free PMC Article
Kinali M, Beeson D, Pitt MC, Jungbluth H, Simonds AK, Aloysius A, Cockerill H, Davis T, Palace J, Manzur AY, Jimenez-Mallebrera C, Sewry C, Muntoni F, Robb SA
J Neuroimmunol 2008 Sep 15;201-202:6-12. Epub 2008 Aug 15 doi: 10.1016/j.jneuroim.2008.06.026. PMID: 18707767

Therapy

Eshaghian T, Rabbani B, Badv RS, Mikaeeli S, Gharib B, Iyadurai S, Mahdieh N
Neurogenetics 2023 Jul;24(3):189-200. Epub 2023 May 25 doi: 10.1007/s10048-023-00719-7. PMID: 37231228
Shao S, Shi G, Bi FF, Huang K
Curr Neuropharmacol 2023;21(7):1594-1605. doi: 10.2174/1570159X21666230126145652. PMID: 36703579
Rodríguez Cruz PM, Hughes I, Manzur A, Munot P, Ramdas S, Wright R, Breen C, Pitt M, Pagnamenta AT, Taylor JC, Palace J, Beeson D
Neuromuscul Disord 2021 Jan;31(1):21-28. Epub 2020 Oct 20 doi: 10.1016/j.nmd.2020.10.006. PMID: 33250374
Hamasaki Y, Hamada R, Muramatsu M, Matsumoto S, Aya K, Ishikura K, Kaneko T, Iijima K
BMC Nephrol 2020 Aug 24;21(1):363. doi: 10.1186/s12882-020-02010-5. PMID: 32838745Free PMC Article
Kinali M, Beeson D, Pitt MC, Jungbluth H, Simonds AK, Aloysius A, Cockerill H, Davis T, Palace J, Manzur AY, Jimenez-Mallebrera C, Sewry C, Muntoni F, Robb SA
J Neuroimmunol 2008 Sep 15;201-202:6-12. Epub 2008 Aug 15 doi: 10.1016/j.jneuroim.2008.06.026. PMID: 18707767

Prognosis

Verschuuren JJ, Palace J, Murai H, Tannemaat MR, Kaminski HJ, Bril V
Lancet Neurol 2022 Feb;21(2):189-202. doi: 10.1016/S1474-4422(21)00463-4. PMID: 35065041
Rodríguez Cruz PM, Hughes I, Manzur A, Munot P, Ramdas S, Wright R, Breen C, Pitt M, Pagnamenta AT, Taylor JC, Palace J, Beeson D
Neuromuscul Disord 2021 Jan;31(1):21-28. Epub 2020 Oct 20 doi: 10.1016/j.nmd.2020.10.006. PMID: 33250374
Shen XM, Di L, Shen S, Zhao Y, Neumeyer AM, Selcen D, Sine SM, Engel AG
Exp Neurol 2020 Sep;331:113375. Epub 2020 Jun 3 doi: 10.1016/j.expneurol.2020.113375. PMID: 32504635Free PMC Article
Cossins J, Liu WW, Belaya K, Maxwell S, Oldridge M, Lester T, Robb S, Beeson D
Hum Mol Genet 2012 Sep 1;21(17):3765-75. Epub 2012 Jun 1 doi: 10.1093/hmg/dds198. PMID: 22661499
Milone M, Shen XM, Selcen D, Ohno K, Brengman J, Iannaccone ST, Harper CM, Engel AG
Neurology 2009 Jul 21;73(3):228-35. doi: 10.1212/WNL.0b013e3181ae7cbc. PMID: 19620612Free PMC Article

Clinical prediction guides

Shen XM, Di L, Shen S, Zhao Y, Neumeyer AM, Selcen D, Sine SM, Engel AG
Exp Neurol 2020 Sep;331:113375. Epub 2020 Jun 3 doi: 10.1016/j.expneurol.2020.113375. PMID: 32504635Free PMC Article
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
Cossins J, Liu WW, Belaya K, Maxwell S, Oldridge M, Lester T, Robb S, Beeson D
Hum Mol Genet 2012 Sep 1;21(17):3765-75. Epub 2012 Jun 1 doi: 10.1093/hmg/dds198. PMID: 22661499
Mohney BG, Pulido JS, Lindor NM, Hogan MC, Consugar MB, Peters J, Pankratz VS, Nasr SH, Smith SJ, Gloor J, Kubly V, Spencer D, Nielson R, Puffenberger EG, Strauss KA, Morton DH, Eldahdah L, Harris PC
Ophthalmology 2011 Jun;118(6):1137-44. Epub 2011 Jan 13 doi: 10.1016/j.ophtha.2010.10.009. PMID: 21236492Free PMC Article
Milone M, Shen XM, Selcen D, Ohno K, Brengman J, Iannaccone ST, Harper CM, Engel AG
Neurology 2009 Jul 21;73(3):228-35. doi: 10.1212/WNL.0b013e3181ae7cbc. PMID: 19620612Free PMC Article

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