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Congenital myopathy 4A, autosomal dominant

MedGen UID:
506993
Concept ID:
CN178536
Disease or Syndrome
Synonyms: Cap myopathy 1; Nemaline myopathy 1
 
Gene (location): TPM3 (1q21.3)
 
Monarch Initiative: MONDO:0800341
OMIM®: 255310

Definition

Congenital myopathy-4A (CMYO4A) is an autosomal dominant disorder of the skeletal muscle characterized by the onset of muscle weakness in infancy or childhood. The severity and pattern of muscle weakness varies, but most affected individuals show mildly delayed motor development, hypotonia, generalized muscle weakness, and weakness of the proximal limb muscles and neck muscles, resulting in difficulty running and easy fatigability. Many patients have respiratory insufficiency with reduced vital capacity, sometimes requiring noninvasive ventilatory assistance. Other common features include myopathic facies, high-arched palate, myasthenia, scapular winging, and scoliosis. Histologic findings on skeletal muscle biopsy are variable, even in patients with the same mutation. Muscle fibers can contain nemaline rod inclusions, subsarcolemmal 'cap' structures, and fiber-type disproportion (Clarke et al., 2008; Waddell et al., 2010; Malfatti et al., 2013). For a discussion of genetic heterogeneity of congenital myopathy, see CMYO1A (117000). For a discussion of genetic heterogeneity of nemaline myopathy, see 256030. [from OMIM]

Professional guidelines

PubMed

Gómez-Oca R, Cowling BS, Laporte J
Int J Mol Sci 2021 Oct 21;22(21) doi: 10.3390/ijms222111377. PMID: 34768808Free PMC Article
Natera-de Benito D, Ortez C, Jou C, Jimenez-Mallebrera C, Codina A, Carrera-García L, Expósito-Escudero J, Cesar S, Martorell L, Gallano P, Gonzalez-Quereda L, Cuadras D, Colomer J, Yubero D, Palau F, Nascimento A
Pediatr Neurol 2021 Feb;115:50-65. Epub 2020 Nov 5 doi: 10.1016/j.pediatrneurol.2020.11.002. PMID: 33333461
Morin G, Biancalana V, Echaniz-Laguna A, Noury JB, Lornage X, Moggio M, Ripolone M, Violano R, Marcorelles P, Maréchal D, Renaud F, Maurage CA, Tard C, Cuisset JM, Laporte J, Böhm J
Hum Mutat 2020 Jan;41(1):17-37. Epub 2019 Sep 15 doi: 10.1002/humu.23899. PMID: 31448844

Recent clinical studies

Etiology

Verdonschot JAJ, Vanhoutte EK, Claes GRF, Helderman-van den Enden ATJM, Hoeijmakers JGJ, Hellebrekers DMEI, de Haan A, Christiaans I, Lekanne Deprez RH, Boen HM, van Craenenbroeck EM, Loeys BL, Hoedemaekers YM, Marcelis C, Kempers M, Brusse E, van Waning JI, Baas AF, Dooijes D, Asselbergs FW, Barge-Schaapveld DQCM, Koopman P, van den Wijngaard A, Heymans SRB, Krapels IPC, Brunner HG
Hum Mutat 2020 Jun;41(6):1091-1111. Epub 2020 Mar 20 doi: 10.1002/humu.24004. PMID: 32112656Free PMC Article
Claeys KG
Dev Med Child Neurol 2020 Mar;62(3):297-302. Epub 2019 Oct 2 doi: 10.1111/dmcn.14365. PMID: 31578728
Butterfield RJ
Continuum (Minneap Minn) 2019 Dec;25(6):1640-1661. doi: 10.1212/CON.0000000000000792. PMID: 31794464
Sewry CA, Laitila JM, Wallgren-Pettersson C
J Muscle Res Cell Motil 2019 Jun;40(2):111-126. Epub 2019 Jun 21 doi: 10.1007/s10974-019-09519-9. PMID: 31228046Free PMC Article
Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC, Soemedi R, Vasli N, Iannaccone ST, Shieh PB, Shur N, Dennison JM, Lawlor MW, Laporte J, Markianos K, Fairbrother WG, Granzier H, Beggs AH
Neurology 2013 Oct 1;81(14):1205-14. Epub 2013 Aug 23 doi: 10.1212/WNL.0b013e3182a6ca62. PMID: 23975875Free PMC Article

Diagnosis

Younger DS
Handb Clin Neurol 2023;195:533-561. doi: 10.1016/B978-0-323-98818-6.00027-3. PMID: 37562885
Lawlor MW, Dowling JJ
Neuromuscul Disord 2021 Oct;31(10):1004-1012. doi: 10.1016/j.nmd.2021.08.003. PMID: 34736623
Claeys KG
Dev Med Child Neurol 2020 Mar;62(3):297-302. Epub 2019 Oct 2 doi: 10.1111/dmcn.14365. PMID: 31578728
Butterfield RJ
Continuum (Minneap Minn) 2019 Dec;25(6):1640-1661. doi: 10.1212/CON.0000000000000792. PMID: 31794464
Sewry CA, Laitila JM, Wallgren-Pettersson C
J Muscle Res Cell Motil 2019 Jun;40(2):111-126. Epub 2019 Jun 21 doi: 10.1007/s10974-019-09519-9. PMID: 31228046Free PMC Article

Therapy

Shieh PB, Kuntz NL, Dowling JJ, Müller-Felber W, Bönnemann CG, Seferian AM, Servais L, Smith BK, Muntoni F, Blaschek A, Foley AR, Saade DN, Neuhaus S, Alfano LN, Beggs AH, Buj-Bello A, Childers MK, Duong T, Graham RJ, Jain M, Coats J, MacBean V, James ES, Lee J, Mavilio F, Miller W, Varfaj F, Murtagh M, Han C, Noursalehi M, Lawlor MW, Prasad S, Rico S
Lancet Neurol 2023 Dec;22(12):1125-1139. doi: 10.1016/S1474-4422(23)00313-7. PMID: 37977713
Tabebordbar M, Lagerborg KA, Stanton A, King EM, Ye S, Tellez L, Krunnfusz A, Tavakoli S, Widrick JJ, Messemer KA, Troiano EC, Moghadaszadeh B, Peacker BL, Leacock KA, Horwitz N, Beggs AH, Wagers AJ, Sabeti PC
Cell 2021 Sep 16;184(19):4919-4938.e22. Epub 2021 Sep 9 doi: 10.1016/j.cell.2021.08.028. PMID: 34506722Free PMC Article
Maani N, Karolczak S, Dowling JJ
Curr Opin Neurol 2021 Oct 1;34(5):727-737. doi: 10.1097/WCO.0000000000000978. PMID: 34267051
Jungbluth H, Muntoni F
Semin Pediatr Neurol 2019 Apr;29:71-82. Epub 2019 Jan 16 doi: 10.1016/j.spen.2019.01.004. PMID: 31060727
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article

Prognosis

Younger DS
Handb Clin Neurol 2023;195:533-561. doi: 10.1016/B978-0-323-98818-6.00027-3. PMID: 37562885
Verdonschot JAJ, Vanhoutte EK, Claes GRF, Helderman-van den Enden ATJM, Hoeijmakers JGJ, Hellebrekers DMEI, de Haan A, Christiaans I, Lekanne Deprez RH, Boen HM, van Craenenbroeck EM, Loeys BL, Hoedemaekers YM, Marcelis C, Kempers M, Brusse E, van Waning JI, Baas AF, Dooijes D, Asselbergs FW, Barge-Schaapveld DQCM, Koopman P, van den Wijngaard A, Heymans SRB, Krapels IPC, Brunner HG
Hum Mutat 2020 Jun;41(6):1091-1111. Epub 2020 Mar 20 doi: 10.1002/humu.24004. PMID: 32112656Free PMC Article
Sewry CA, Laitila JM, Wallgren-Pettersson C
J Muscle Res Cell Motil 2019 Jun;40(2):111-126. Epub 2019 Jun 21 doi: 10.1007/s10974-019-09519-9. PMID: 31228046Free PMC Article
Jungbluth H, Wallgren-Pettersson C, Laporte J
Orphanet J Rare Dis 2008 Sep 25;3:26. doi: 10.1186/1750-1172-3-26. PMID: 18817572Free PMC Article
Jungbluth H
Orphanet J Rare Dis 2007 May 15;2:25. doi: 10.1186/1750-1172-2-25. PMID: 17504518Free PMC Article

Clinical prediction guides

Fusto A, Cassandrini D, Fiorillo C, Codemo V, Astrea G, D'Amico A, Maggi L, Magri F, Pane M, Tasca G, Sabbatini D, Bello L, Battini R, Bernasconi P, Fattori F, Bertini ES, Comi G, Messina S, Mongini T, Moroni I, Panicucci C, Berardinelli A, Donati A, Nigro V, Pini A, Giannotta M, Dosi C, Ricci E, Mercuri E, Minervini G, Tosatto S, Santorelli F, Bruno C, Pegoraro E
Acta Neuropathol Commun 2022 Apr 15;10(1):54. doi: 10.1186/s40478-022-01357-0. PMID: 35428369Free PMC Article
Lawlor MW, Dowling JJ
Neuromuscul Disord 2021 Oct;31(10):1004-1012. doi: 10.1016/j.nmd.2021.08.003. PMID: 34736623
Amburgey K, Acker M, Saeed S, Amin R, Beggs AH, Bönnemann CG, Brudno M, Constantinescu A, Dastgir J, Diallo M, Genetti CA, Glueck M, Hewson S, Hum C, Jain MS, Lawlor MW, Meyer OH, Nelson L, Sultanum N, Syed F, Tran T, Wang CH, Dowling JJ
Neurology 2021 Mar 9;96(10):e1425-e1436. Epub 2021 Jan 4 doi: 10.1212/WNL.0000000000011458. PMID: 33397769Free PMC Article
Nicolau S, Kao JC, Liewluck T
Muscle Nerve 2019 Dec;60(6):648-657. Epub 2019 Sep 10 doi: 10.1002/mus.26676. PMID: 31449669
Rudnik-Schöneborn S, Wallgren-Pettersson C
Semin Pediatr Neurol 2019 Apr;29:23-29. Epub 2019 Jan 16 doi: 10.1016/j.spen.2019.01.006. PMID: 31060722

Recent systematic reviews

Buchignani B, Marinella G, Pasquariello R, Sgherri G, Frosini S, Santorelli FM, Orsini A, Battini R, Astrea G
Genes (Basel) 2024 Feb 5;15(2) doi: 10.3390/genes15020208. PMID: 38397198Free PMC Article
Middelink M, Voermans NC, van Engelen BGM, Janssen MCH, Groothuis JT, Knuijt S, Zweers-van Essen H
J Neuromuscul Dis 2023;10(5):777-785. doi: 10.3233/JND-230014. PMID: 37483025Free PMC Article
Christophers B, Lopez MA, Gupta VA, Vogel H, Baylies M
J Child Neurol 2022 Jun;37(7):652-663. Epub 2022 Jun 7 doi: 10.1177/08830738221096316. PMID: 36960434Free PMC Article

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