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Congenital myopathy 11(MYONP; CMYP11)

MedGen UID:
462881
Concept ID:
C3151531
Disease or Syndrome
Synonym: Myopathy, congenital, nonprogressive
 
Gene (location): HACD1 (10p12.33)
 
Monarch Initiative: MONDO:0859264
OMIM®: 619967

Definition

Congenital myopathy-11 (CMYP11) is an autosomal recessive skeletal muscle disorder characterized clinically by severe hypotonia apparent at birth, resulting in early feeding problems, motor delay, and walking difficulties. However, the course of the disease is nonprogressive: most affected individuals achieve independent ambulation and tend to show improvement of muscle weakness throughout childhood and early adulthood. There is no respiratory or cardiac involvement; cognitive development is normal. Muscle biopsy may show rare centralized nuclei, type 1 fiber hypotrophy, and type 1 fiber predominance, suggestive of a pathologic diagnosis of congenital fiber-type disproportion (CFTD). However, the findings on skeletal muscle biopsy may be nonspecific (Muhammad et al., 2013). For a discussion of genetic heterogeneity of congenital myopathy, see CMYP1A (117000). [from OMIM]

Clinical features

From HPO
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
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.
Waddling gait
MedGen UID:
66667
Concept ID:
C0231712
Finding
Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
Gowers sign
MedGen UID:
65865
Concept ID:
C0234182
Finding
A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.
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).
Apneic episodes in infancy
MedGen UID:
814310
Concept ID:
C3807980
Finding
Recurrent episodes of apnea occurring during infancy.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Abnormal circulating creatine kinase concentration
MedGen UID:
868058
Concept ID:
C4022449
Finding
Any deviation from the normal circulating creatine kinase concentration.
Weak cry
MedGen UID:
65892
Concept ID:
C0234860
Finding
Breech presentation
MedGen UID:
654
Concept ID:
C0006157
Pathologic Function
A position of the fetus at delivery in which the fetus enters the birth canal with the buttocks or feet first.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Abnormal activity of mitochondrial respiratory chain
MedGen UID:
868721
Concept ID:
C4023126
Finding
An increased or decreased activity of the mitochondrial respiratory chain.

Professional guidelines

PubMed

Kong L, Li S, Zhao Z, Feng J, Fu X, Li H, Zhu J, Wang Y, Tang W, Yuan C, Li F, Han X, Wu D, Kong X, Sun L
Clin Genet 2024 Jan;105(1):52-61. Epub 2023 Oct 11 doi: 10.1111/cge.14434. PMID: 37822034
Al Kaissi A, Kenis V, Jemaa LB, Sassi H, Shboul M, Grill F, Ganger R, Kircher SG
Clin Rheumatol 2020 Feb;39(2):553-560. Epub 2019 Oct 18 doi: 10.1007/s10067-019-04783-z. PMID: 31628567
Maggi L, Bernasconi P, D'Amico A, Brugnoni R, Fiorillo C, Garibaldi M, Astrea G, Bruno C, Santorelli FM, Liguori R, Antonini G, Evoli A, Bertini E, Rodolico C, Mantegazza R
Neurol Sci 2019 Mar;40(3):457-468. Epub 2018 Dec 15 doi: 10.1007/s10072-018-3682-x. PMID: 30554356

Recent clinical studies

Etiology

Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators
Neurology 2023 Jul 18;101(3):e238-e252. Epub 2023 Jun 2 doi: 10.1212/WNL.0000000000207402. PMID: 37268435Free PMC Article
Williams CA, Wadey C, Pieles G, Stuart G, Taylor RS, Long L
Cochrane Database Syst Rev 2020 Oct 28;10(10):CD013400. doi: 10.1002/14651858.CD013400.pub2. PMID: 33112424Free PMC Article
Warman Chardon J, Díaz-Manera J, Tasca G, Bönnemann CG, Gómez-Andrés D, Heerschap A, Mercuri E, Muntoni F, Pichiecchio A, Ricci E, Walter MC, Hanna M, Jungbluth H, Morrow JM, Fernández-Torrón R, Udd B, Vissing J, Yousry T, Quijano-Roy S, Straub V, Carlier RY; MYO-MRI Working Group
Neuromuscul Disord 2019 Nov;29(11):827-841. Epub 2019 Sep 16 doi: 10.1016/j.nmd.2019.08.011. PMID: 31727541
Cassandrini D, Trovato R, Rubegni A, Lenzi S, Fiorillo C, Baldacci J, Minetti C, Astrea G, Bruno C, Santorelli FM; Italian Network on Congenital Myopathies
Ital J Pediatr 2017 Nov 15;43(1):101. doi: 10.1186/s13052-017-0419-z. PMID: 29141652Free PMC Article
Bornemann A, Goebel HH
Brain Pathol 2001 Apr;11(2):206-17. doi: 10.1111/j.1750-3639.2001.tb00393.x. PMID: 11303796Free PMC Article

Diagnosis

Brunklaus A, Brünger T, Feng T, Fons C, Lehikoinen A, Panagiotakaki E, Vintan MA, Symonds J, Andrew J, Arzimanoglou A, Delima S, Gallois J, Hanrahan D, Lesca G, MacLeod S, Marjanovic D, McTague A, Nuñez-Enamorado N, Perez-Palma E, Scott Perry M, Pysden K, Russ-Hall SJ, Scheffer IE, Sully K, Syrbe S, Vaher U, Velayutham M, Vogt J, Weiss S, Wirrell E, Zuberi SM, Lal D, Møller RS, Mantegazza M, Cestèle S
Brain 2022 Nov 21;145(11):3816-3831. doi: 10.1093/brain/awac210. PMID: 35696452Free PMC Article
Ogasawara M, Nishino I
Neuromuscul Disord 2021 Oct;31(10):968-977. Epub 2021 Sep 17 doi: 10.1016/j.nmd.2021.08.015. PMID: 34627702
Williams CA, Wadey C, Pieles G, Stuart G, Taylor RS, Long L
Cochrane Database Syst Rev 2020 Oct 28;10(10):CD013400. doi: 10.1002/14651858.CD013400.pub2. PMID: 33112424Free PMC Article
Gonzalez-Quereda L, Rodriguez MJ, Diaz-Manera J, Alonso-Perez J, Gallardo E, Nascimento A, Ortez C, Natera-de Benito D, Olive M, Gonzalez-Mera L, Munain AL, Zulaica M, Poza JJ, Jerico I, Torne L, Riera P, Milisenda J, Sanchez A, Garrabou G, Llano I, Madruga-Garrido M, Gallano P
Genes (Basel) 2020 May 11;11(5) doi: 10.3390/genes11050539. PMID: 32403337Free PMC Article
Warman Chardon J, Díaz-Manera J, Tasca G, Bönnemann CG, Gómez-Andrés D, Heerschap A, Mercuri E, Muntoni F, Pichiecchio A, Ricci E, Walter MC, Hanna M, Jungbluth H, Morrow JM, Fernández-Torrón R, Udd B, Vissing J, Yousry T, Quijano-Roy S, Straub V, Carlier RY; MYO-MRI Working Group
Neuromuscul Disord 2019 Nov;29(11):827-841. Epub 2019 Sep 16 doi: 10.1016/j.nmd.2019.08.011. PMID: 31727541

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
Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators
Neurology 2023 Jul 18;101(3):e238-e252. Epub 2023 Jun 2 doi: 10.1212/WNL.0000000000207402. PMID: 37268435Free PMC Article
Williams CA, Wadey C, Pieles G, Stuart G, Taylor RS, Long L
Cochrane Database Syst Rev 2020 Oct 28;10(10):CD013400. doi: 10.1002/14651858.CD013400.pub2. PMID: 33112424Free PMC Article
Jungbluth H, Treves S, Zorzato F, Sarkozy A, Ochala J, Sewry C, Phadke R, Gautel M, Muntoni F
Nat Rev Neurol 2018 Mar;14(3):151-167. Epub 2018 Feb 2 doi: 10.1038/nrneurol.2017.191. PMID: 29391587
Jungbluth H, Ochala J, Treves S, Gautel M
Semin Cell Dev Biol 2017 Apr;64:191-200. Epub 2016 Aug 8 doi: 10.1016/j.semcdb.2016.08.004. PMID: 27515125

Prognosis

Williams CA, Wadey C, Pieles G, Stuart G, Taylor RS, Long L
Cochrane Database Syst Rev 2020 Oct 28;10(10):CD013400. doi: 10.1002/14651858.CD013400.pub2. PMID: 33112424Free PMC Article
Jungbluth H, Treves S, Zorzato F, Sarkozy A, Ochala J, Sewry C, Phadke R, Gautel M, Muntoni F
Nat Rev Neurol 2018 Mar;14(3):151-167. Epub 2018 Feb 2 doi: 10.1038/nrneurol.2017.191. PMID: 29391587
Farruggia P, Di Marco F, Dufour C
Expert Rev Hematol 2018 Mar;11(3):239-246. Epub 2018 Jan 23 doi: 10.1080/17474086.2018.1426454. PMID: 29337599
Cassandrini D, Trovato R, Rubegni A, Lenzi S, Fiorillo C, Baldacci J, Minetti C, Astrea G, Bruno C, Santorelli FM; Italian Network on Congenital Myopathies
Ital J Pediatr 2017 Nov 15;43(1):101. doi: 10.1186/s13052-017-0419-z. PMID: 29141652Free PMC Article
Goebel HH, Warlo IA
Neuromuscul Disord 2001 Jan;11(1):3-6. doi: 10.1016/s0960-8966(00)00165-6. PMID: 11166159

Clinical prediction guides

Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, Goldstein A, Gorman GS, Haas R, Hirano M, Klopstock T, Koenig MK, Kornblum C, Lamperti C, Lehman A, Longo N, Molnar MJ, Parikh S, Phan H, Pitceathly RDS, Saneto R, Scaglia F, Servidei S, Tarnopolsky M, Toscano A, Van Hove JLK, Vissing J, Vockley J, Finman JS, Brown DA, Shiffer JA, Mancuso M; MMPOWER-3 Trial Investigators
Neurology 2023 Jul 18;101(3):e238-e252. Epub 2023 Jun 2 doi: 10.1212/WNL.0000000000207402. PMID: 37268435Free PMC Article
Gurgel-Giannetti J, Souza LS, Yamamoto GL, Belisario M, Lazar M, Campos W, Pavanello RCM, Zatz M, Reed U, Zanoteli E, Oliveira AB, Lehtokari VL, Casella EB, Machado-Costa MC, Wallgren-Pettersson C, Laing NG, Nigro V, Vainzof M
Int J Mol Sci 2022 Oct 9;23(19) doi: 10.3390/ijms231911995. PMID: 36233295Free PMC Article
Mroczek M, Longman C, Farrugia ME, Kapetanovic Garcia S, Ardicli D, Topaloglu H, Hernández-Laín A, Orhan D, Alikasifoglu M, Duff J, Specht S, Nowak K, Ravenscroft G, Chao K, Valivullah Z, Donkervoort S, Saade D, Bönnemann C, Straub V, Yoon G
J Med Genet 2022 Nov;59(11):1069-1074. Epub 2022 Apr 7 doi: 10.1136/jmedgenet-2021-108341. PMID: 35393337Free PMC Article
Piché J, Van Vliet PP, Pucéat M, Andelfinger G
Cell Cycle 2019 Nov;18(21):2828-2848. Epub 2019 Sep 13 doi: 10.1080/15384101.2019.1658476. PMID: 31516082Free PMC Article
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

Minervini G, Franco R, Marrapodi MM, Fiorillo L, Cervino G, Cicciù M
J Oral Rehabil 2023 Jul;50(7):627-634. Epub 2023 Apr 19 doi: 10.1111/joor.13458. PMID: 37021601
Jeffery TC, Chang AB, Conwell LS
Cochrane Database Syst Rev 2023 Jan 10;1(1):CD002010. doi: 10.1002/14651858.CD002010.pub5. PMID: 36625789Free PMC Article
Williams CA, Wadey C, Pieles G, Stuart G, Taylor RS, Long L
Cochrane Database Syst Rev 2020 Oct 28;10(10):CD013400. doi: 10.1002/14651858.CD013400.pub2. PMID: 33112424Free PMC Article
Martins-Filho PR, Souza Tavares CS, Araújo Carvalho AC, Reis MCDS, Santos HP Jr, Santos VS
Pediatr Neurol 2020 Sep;110:20-24. Epub 2020 May 25 doi: 10.1016/j.pediatrneurol.2020.05.007. PMID: 32646676
Mah JK, Korngut L, Fiest KM, Dykeman J, Day LJ, Pringsheim T, Jette N
Can J Neurol Sci 2016 Jan;43(1):163-77. doi: 10.1017/cjn.2015.311. PMID: 26786644

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