U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Congenital myasthenic syndrome 8(CMSPPD; CMS8)

MedGen UID:
815069
Concept ID:
C3808739
Disease or Syndrome
Synonyms: Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects; MYASTHENIC SYNDROME, CONGENITAL, DUE TO AGRIN DEFICIENCY
 
Gene (location): AGRN (1p36.33)
 
Monarch Initiative: MONDO:0014052
OMIM®: 615120

Definition

Congenital myasthenic syndromes are genetic disorders of the neuromuscular junction (NMJ) that are classified by the site of the transmission defect: presynaptic, synaptic, and postsynaptic. CMS8 is an autosomal recessive disorder characterized by prominent defects of both the pre- and postsynaptic regions. Affected individuals have onset of muscle weakness in early childhood; the severity of the weakness and muscles affected is variable (summary by Maselli et al., 2012). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). [from OMIM]

Additional description

From MedlinePlus Genetics
Some individuals have episodes of breathing problems that may be triggered by fevers or infection. Severely affected individuals may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis).

Congenital myasthenic syndrome is a group of conditions characterized by muscle weakness (myasthenia) that worsens with physical exertion. The muscle weakness typically begins in early childhood but can also appear in adolescence or adulthood. Facial muscles, including muscles that control the eyelids, muscles that move the eyes, and muscles used for chewing and swallowing, are most commonly affected. However, any of the muscles used for movement (skeletal muscles) can be affected in this condition. Due to muscle weakness, affected infants may have feeding difficulties. Development of motor skills such as crawling or walking may be delayed. The severity of the myasthenia varies greatly, with some people experiencing minor weakness and others having such severe weakness that they are unable to walk.  https://medlineplus.gov/genetics/condition/congenital-myasthenic-syndrome

Clinical features

From HPO
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Weakness of facial musculature
MedGen UID:
98103
Concept ID:
C0427055
Disease or Syndrome
Reduced strength of one or more muscles innervated by the facial nerve (the seventh cranial nerve).
Difficulty running
MedGen UID:
108251
Concept ID:
C0560346
Finding
Reduced ability to run.
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.
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.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
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).

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
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145
Harper CM, Fukodome T, Engel AG
Neurology 2003 May 27;60(10):1710-3. doi: 10.1212/01.wnl.0000061483.11417.1b. PMID: 12771277

Recent clinical studies

Etiology

Polavarapu K, Sunitha B, Töpf A, Preethish-Kumar V, Thompson R, Vengalil S, Nashi S, Bardhan M, Sanka SB, Huddar A, Unnikrishnan G, Arunachal G, Girija MS, Porter A, Azuma Y, Lorenzoni PJ, Baskar D, Anjanappa RM, Keertipriya M, Padmanabh H, Harikrishna GV, Laurie S, Matalonga L, Horvath R, Nalini A, Lochmüller H
Brain 2024 Jan 4;147(1):281-296. doi: 10.1093/brain/awad315. PMID: 37721175Free PMC Article
Estephan EP, Zambon AA, Thompson R, Polavarapu K, Jomaa D, Töpf A, Helito PVP, Heise CO, Moreno CAM, Silva AMS, Kouyoumdjian JA, Morita MDP, Reed UC, Lochmüller H, Zanoteli E
Eur J Neurol 2022 Mar;29(3):833-842. Epub 2021 Nov 17 doi: 10.1111/ene.15173. PMID: 34749429
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
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Belaya K, Rodríguez Cruz PM, Liu WW, Maxwell S, McGowan S, Farrugia ME, Petty R, Walls TJ, Sedghi M, Basiri K, Yue WW, Sarkozy A, Bertoli M, Pitt M, Kennett R, Schaefer A, Bushby K, Parton M, Lochmüller H, Palace J, Muntoni F, Beeson D
Brain 2015 Sep;138(Pt 9):2493-504. Epub 2015 Jun 30 doi: 10.1093/brain/awv185. PMID: 26133662Free PMC Article

Diagnosis

Polavarapu K, Sunitha B, Töpf A, Preethish-Kumar V, Thompson R, Vengalil S, Nashi S, Bardhan M, Sanka SB, Huddar A, Unnikrishnan G, Arunachal G, Girija MS, Porter A, Azuma Y, Lorenzoni PJ, Baskar D, Anjanappa RM, Keertipriya M, Padmanabh H, Harikrishna GV, Laurie S, Matalonga L, Horvath R, Nalini A, Lochmüller H
Brain 2024 Jan 4;147(1):281-296. doi: 10.1093/brain/awad315. PMID: 37721175Free PMC Article
Gilhus NE
Handb Clin Neurol 2023;195:635-652. doi: 10.1016/B978-0-323-98818-6.00010-8. PMID: 37562891
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Engel AG
Curr Neurol Neurosci Rep 2018 Jun 12;18(8):46. doi: 10.1007/s11910-018-0852-4. PMID: 29892917
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

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
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
Al-Muhaizea MA, AlQuait L, AlRasheed A, AlHarbi S, Albader AA, AlMass R, Albakheet A, Alhumaidan A, AlRasheed MM, Colak D, Kaya N
Neuromuscul Disord 2020 Jul;30(7):611-615. Epub 2020 May 15 doi: 10.1016/j.nmd.2020.04.007. PMID: 32616363
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article
Ito M, Ohno K
Matrix Biol 2018 Aug;68-69:628-636. Epub 2018 Feb 20 doi: 10.1016/j.matbio.2018.02.014. PMID: 29475025

Prognosis

Gilhus NE
Handb Clin Neurol 2023;195:635-652. doi: 10.1016/B978-0-323-98818-6.00010-8. PMID: 37562891
Tsalta-Mladenov M, Levkova M, Georgieva D, Andonova S
J Am Assoc Nurse Pract 2023 Aug 1;35(8):519-523. doi: 10.1097/JXX.0000000000000878. PMID: 37141567
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
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
Durmus H, Shen XM, Serdaroglu-Oflazer P, Kara B, Parman-Gulsen Y, Ozdemir C, Brengman J, Deymeer F, Engel AG
Neuromuscul Disord 2018 Apr;28(4):315-322. Epub 2017 Nov 28 doi: 10.1016/j.nmd.2017.11.013. PMID: 29395675Free PMC Article

Clinical prediction guides

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
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
Luan X, Tian W, Cao L
Clin Neurol Neurosurg 2016 Nov;150:41-45. Epub 2016 Aug 22 doi: 10.1016/j.clineuro.2016.08.021. PMID: 27588369
Witting N, Vissing J
JAMA Neurol 2014 Mar;71(3):350-4. doi: 10.1001/jamaneurol.2013.5590. PMID: 24425145
Harper CM, Fukodome T, Engel AG
Neurology 2003 May 27;60(10):1710-3. doi: 10.1212/01.wnl.0000061483.11417.1b. PMID: 12771277

Recent systematic reviews

Desaphy JF, Altamura C, Vicart S, Fontaine B
J Neuromuscul Dis 2021;8(3):357-381. doi: 10.3233/JND-200582. PMID: 33325393Free PMC Article
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...