U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Autosomal dominant centronuclear myopathy(CNM1)

MedGen UID:
1645741
Concept ID:
C4551952
Disease or Syndrome
Synonyms: Myopathy, centronuclear, 1; Myopathy, centronuclear, 3; MYOTUBULAR MYOPATHY, AUTOSOMAL DOMINANT
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): DNM2 (19p13.2); MTMR14 (3p25.3)
 
Monarch Initiative: MONDO:0008048
OMIM®: 160150
Orphanet: ORPHA169189

Definition

Centronuclear myopathy-1 (CNM1) is an autosomal dominant congenital myopathy characterized by slowly progressive muscular weakness and wasting. The disorder involves mainly limb girdle, trunk, and neck muscles but may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life, and some affected individuals become wheelchair-bound in their fifties. Ptosis and limitation of eye movements occur frequently. The most prominent histopathologic features include high frequency of centrally located nuclei in a large number of extrafusal muscle fibers (which is the basis of the name of the disorder), radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers (summary by Bitoun et al., 2005). Genetic Heterogeneity of Centronuclear Myopathy Centronuclear myopathy is a genetically heterogeneous disorder. See also X-linked CNM (CNMX; 310400), caused by mutation in the MTM1 gene (300415) on chromosome Xq28; CNM2 (255200), caused by mutation in the BIN1 gene (601248) on chromosome 2q14; CNM4 (614807), caused by mutation in the CCDC78 gene (614666) on chromosome 16p13; CNM5 (615959), caused by mutation in the SPEG gene (615950) on chromosome 2q35; and CNM6 (617760), caused by mutation in the ZAK gene (609479) on chromosome 2q31. The mutation in the MYF6 gene that was reported to cause a form of CNM, formerly designated CNM3, has been reclassified as a variant of unknown significance; see 159991.0001. Some patients with mutation in the RYR1 gene (180901) have findings of centronuclear myopathy on skeletal muscle biopsy (see 255320). [from OMIM]

Clinical features

From HPO
Distal lower limb muscle weakness
MedGen UID:
324514
Concept ID:
C1836450
Finding
Reduced strength of the distal musculature of the legs.
Muscle fibrillation
MedGen UID:
65418
Concept ID:
C0231531
Finding
Fine, rapid twitching of individual muscle fibers with little or no movement of the muscle as a whole as ascertained by electromyography (EMG). If a motor neuron or its axon is destroyed, the muscle fibers it innervates undergo denervation atrophy. This leads to hypersensitivity of individual muscle fibers to acetyl choline so that they may contract spontaneously. Isolated activity of individual muscle fibers is generally so fine it cannot be seen through the intact skin, although it can be recorded as a short-duration spike in the EMG.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Neck muscle weakness
MedGen UID:
66808
Concept ID:
C0240479
Finding
Decreased strength of the neck musculature.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
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.
Achilles tendon contracture
MedGen UID:
98052
Concept ID:
C0410264
Anatomical Abnormality
A contracture of the Achilles tendon.
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).
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
EMG: positive sharp waves
MedGen UID:
607215
Concept ID:
C0429349
Finding
These are spontaneous firing action potentials stimulated by needle movement of an injured muscle fiber. There is propagation to, but not past, the needle tip. This inhibits the display of the negative deflection of the waveform.
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Centrally nucleated skeletal muscle fibers
MedGen UID:
330782
Concept ID:
C1842170
Finding
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
Proximal amyotrophy
MedGen UID:
342591
Concept ID:
C1850794
Disease or Syndrome
Amyotrophy (muscular atrophy) affecting the proximal musculature.
Type 1 muscle fiber predominance
MedGen UID:
344274
Concept ID:
C1854387
Finding
An abnormal predominance of type I muscle fibers (in general, this feature can only be observed on muscle biopsy).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Proximal muscle weakness in upper limbs
MedGen UID:
356424
Concept ID:
C1866012
Finding
A lack of strength of the proximal muscles of the arms.
Proximal upper limb amyotrophy
MedGen UID:
356138
Concept ID:
C1866013
Finding
Muscular atrophy affecting proximally located muscles of the arms.
Skeletal muscle hypertrophy
MedGen UID:
853739
Concept ID:
C2265792
Finding
Abnormal increase in muscle size and mass not due to training.
EMG: myopathic abnormalities
MedGen UID:
867362
Concept ID:
C4021726
Pathologic Function
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
EMG: myotonic discharges
MedGen UID:
867779
Concept ID:
C4022169
Finding
High frequency discharges in electromyography (EMG) that vary in amplitude and frequency, waxing and waning continuously with firing frequencies ranging from 150/second down to 20/second and producing a sound that has been referred to as a dive bomber sound.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Mildly elevated creatine kinase
MedGen UID:
342469
Concept ID:
C1850309
Finding
Sleepy facial expression
MedGen UID:
870757
Concept ID:
C4025214
Finding
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).
External ophthalmoplegia
MedGen UID:
57662
Concept ID:
C0162292
Disease or Syndrome
Paralysis of the external ocular muscles.
Ophthalmoparesis
MedGen UID:
155551
Concept ID:
C0751401
Sign or Symptom
Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Böhm J, Biancalana V, Dechene ET, Bitoun M, Pierson CR, Schaefer E, Karasoy H, Dempsey MA, Klein F, Dondaine N, Kretz C, Haumesser N, Poirson C, Toussaint A, Greenleaf RS, Barger MA, Mahoney LJ, Kang PB, Zanoteli E, Vissing J, Witting N, Echaniz-Laguna A, Wallgren-Pettersson C, Dowling J, Merlini L, Oldfors A, Bomme Ousager L, Melki J, Krause A, Jern C, Oliveira AS, Petit F, Jacquette A, Chaussenot A, Mowat D, Leheup B, Cristofano M, Poza Aldea JJ, Michel F, Furby A, Llona JE, Van Coster R, Bertini E, Urtizberea JA, Drouin-Garraud V, Béroud C, Prudhon B, Bedford M, Mathews K, Erby LA, Smith SA, Roggenbuck J, Crowe CA, Brennan Spitale A, Johal SC, Amato AA, Demmer LA, Jonas J, Darras BT, Bird TD, Laurino M, Welt SI, Trotter C, Guicheney P, Das S, Mandel JL, Beggs AH, Laporte J
Hum Mutat 2012 Jun;33(6):949-59. Epub 2012 Apr 4 doi: 10.1002/humu.22067. PMID: 22396310Free PMC Article

Curated

Biancalana V, Beggs AH, Das S, Jungbluth H, Kress W, Nishino I, North K, Romero NB, Laporte J
Eur J Hum Genet 2012 Oct;20(10) Epub 2012 May 23 doi: 10.1038/ejhg.2012.91. PMID: 22617344Free PMC Article

Recent clinical studies

Etiology

Mori-Yoshimura M, Okuma A, Oya Y, Fujimura-Kiyono C, Nakajima H, Matsuura K, Takemura A, Malicdan MC, Hayashi YK, Nonaka I, Murata M, Nishino I
Clin Neurol Neurosurg 2012 Jul;114(6):678-83. Epub 2012 May 19 doi: 10.1016/j.clineuro.2011.10.040. PMID: 22613877
Felice KJ, Grunnet ML
Muscle Nerve 1997 Sep;20(9):1194-6. doi: 10.1002/(sici)1097-4598(199709)20:9<1194::aid-mus19>3.0.co;2-t. PMID: 9270681

Diagnosis

Mohar NP, Cox EM, Adelizzi E, Moore SA, Mathews KD, Darbro BW, Wallrath LL
Int J Mol Sci 2024 Apr 30;25(9) doi: 10.3390/ijms25094930. PMID: 38732148Free PMC Article
Lin P, Liu X, Zhao D, Dai T, Wu H, Gong Y, Yan C
Neurol Sci 2016 Jun;37(6):995-8. Epub 2016 Feb 23 doi: 10.1007/s10072-016-2513-1. PMID: 26908122
Böhm J, Biancalana V, Malfatti E, Dondaine N, Koch C, Vasli N, Kress W, Strittmatter M, Taratuto AL, Gonorazky H, Laforêt P, Maisonobe T, Olivé M, Gonzalez-Mera L, Fardeau M, Carrière N, Clavelou P, Eymard B, Bitoun M, Rendu J, Fauré J, Weis J, Mandel JL, Romero NB, Laporte J
Brain 2014 Dec;137(Pt 12):3160-70. Epub 2014 Sep 25 doi: 10.1093/brain/awu272. PMID: 25260562
Böhm J, Biancalana V, Dechene ET, Bitoun M, Pierson CR, Schaefer E, Karasoy H, Dempsey MA, Klein F, Dondaine N, Kretz C, Haumesser N, Poirson C, Toussaint A, Greenleaf RS, Barger MA, Mahoney LJ, Kang PB, Zanoteli E, Vissing J, Witting N, Echaniz-Laguna A, Wallgren-Pettersson C, Dowling J, Merlini L, Oldfors A, Bomme Ousager L, Melki J, Krause A, Jern C, Oliveira AS, Petit F, Jacquette A, Chaussenot A, Mowat D, Leheup B, Cristofano M, Poza Aldea JJ, Michel F, Furby A, Llona JE, Van Coster R, Bertini E, Urtizberea JA, Drouin-Garraud V, Béroud C, Prudhon B, Bedford M, Mathews K, Erby LA, Smith SA, Roggenbuck J, Crowe CA, Brennan Spitale A, Johal SC, Amato AA, Demmer LA, Jonas J, Darras BT, Bird TD, Laurino M, Welt SI, Trotter C, Guicheney P, Das S, Mandel JL, Beggs AH, Laporte J
Hum Mutat 2012 Jun;33(6):949-59. Epub 2012 Apr 4 doi: 10.1002/humu.22067. PMID: 22396310Free PMC Article
Susman RD, Quijano-Roy S, Yang N, Webster R, Clarke NF, Dowling J, Kennerson M, Nicholson G, Biancalana V, Ilkovski B, Flanigan KM, Arbuckle S, Malladi C, Robinson P, Vucic S, Mayer M, Romero NB, Urtizberea JA, García-Bragado F, Guicheney P, Bitoun M, Carlier RY, North KN
Neuromuscul Disord 2010 Apr;20(4):229-37. Epub 2010 Mar 12 doi: 10.1016/j.nmd.2010.02.016. PMID: 20227276

Therapy

Trochet D, Prudhon B, Beuvin M, Peccate C, Lorain S, Julien L, Benkhelifa-Ziyyat S, Rabai A, Mamchaoui K, Ferry A, Laporte J, Guicheney P, Vassilopoulos S, Bitoun M
EMBO Mol Med 2018 Feb;10(2):239-253. doi: 10.15252/emmm.201707988. PMID: 29246969Free PMC Article

Prognosis

Felice KJ, Grunnet ML
Muscle Nerve 1997 Sep;20(9):1194-6. doi: 10.1002/(sici)1097-4598(199709)20:9<1194::aid-mus19>3.0.co;2-t. PMID: 9270681

Clinical prediction guides

Lopergolo D, Gallus GN, Pieraccini G, Boscaro F, Berti G, Serni G, Volpi N, Formichi P, Bianchi S, Cassandrini D, Sorrentino V, Rossi D, Santorelli FM, De Stefano N, Malandrini A
Cells 2024 Sep 8;13(17) doi: 10.3390/cells13171504. PMID: 39273074Free PMC Article
Haberlová J, Mazanec R, Ridzoň P, Baránková L, Nürnberg G, Nürnberg P, Sticht H, Huehne K, Seeman P, Rautenstrauss B
J Neurogenet 2011 Dec;25(4):182-8. doi: 10.3109/01677063.2011.627484. PMID: 22091729
Liewluck T, Lovell TL, Bite AV, Engel AG
Neuromuscul Disord 2010 Dec;20(12):801-4. doi: 10.1016/j.nmd.2010.07.273. PMID: 20817456Free 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.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • EuroGenetest, 2012
      Clinical utility gene card for: Centronuclear and myotubular myopathies.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...