U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

X-linked myopathy with excessive autophagy(AVM)

MedGen UID:
374264
Concept ID:
C1839615
Disease or Syndrome
Synonyms: Autophagic vacuolar myopathy; AVM; Vacuolar myopathy
SNOMED CT: X-linked myopathy with excessive autophagy (719815005); Vacuolar myopathy (719815005)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): VMA21 (Xq28)
 
Monarch Initiative: MONDO:0010684
OMIM®: 310440
Orphanet: ORPHA25980

Definition

X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive skeletal muscle disorder characterized by childhood onset of progressive muscle weakness and atrophy primarily affecting the proximal muscles. While onset is usually in childhood, it can range from infancy to adulthood. Many patients lose ambulation and become wheelchair-bound. Other organ systems, including the heart, are clinically unaffected. Muscle biopsy shows intracytoplasmic autophagic vacuoles with sarcolemmal features and a multilayered basal membrane (summary by Ramachandran et al., 2013; Kurashige et al., 2013, and Ruggieri et al., 2015). Danon disease (300257), caused by mutation in the LAMP2 gene (309060) on chromosome Xq24, is a distinct disorder with similar pathologic features. [from OMIM]

Clinical features

From HPO
Abnormality of the cardiovascular system
MedGen UID:
116727
Concept ID:
C0243050
Congenital Abnormality
Any abnormality of the cardiovascular system.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
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.
Difficulty climbing stairs
MedGen UID:
68676
Concept ID:
C0239067
Finding
Reduced ability to climb stairs.
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.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Difficulty running
MedGen UID:
108251
Concept ID:
C0560346
Finding
Reduced ability to run.
Myotonia
MedGen UID:
675119
Concept ID:
C0700153
Finding
An involuntary and painless delay in the relaxation of skeletal muscle following contraction or electrical stimulation.
Proximal lower limb amyotrophy
MedGen UID:
373171
Concept ID:
C1836767
Finding
Muscular atrophy affecting proximally located muscles of the legs, i.e., of the thigh.
Muscle fiber necrosis
MedGen UID:
376893
Concept ID:
C1850848
Pathologic Function
Abnormal cell death involving muscle fibers usually associated with break in, or absence of, muscle surface fiber membrane and resulting in irreversible damage to muscle fibers.
Proximal muscle weakness in lower limbs
MedGen UID:
356423
Concept ID:
C1866010
Finding
A lack of strength of the proximal muscles of the legs.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Skeletal muscle autophagosome accumulation
MedGen UID:
1814214
Concept ID:
C5676640
Finding
Abnormal accumulation of autophagosomes in skeletal muscle tissue.
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.
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.
Limited extraocular movements
MedGen UID:
388060
Concept ID:
C1858427
Finding
Limited mobility of the eye within its socket.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVX-linked myopathy with excessive autophagy
Follow this link to review classifications for X-linked myopathy with excessive autophagy in Orphanet.

Recent clinical studies

Etiology

Fernández-Eulate G, Alfieri G, Spinazzi M, Ackermann-Bonan I, Duval F, Solé G, Caillon F, Mercier S, Pereon Y, Magot A, Pegat A, Salort-Campana E, Chabrol B, Gorokhova S, Krahn M, Biancalana V, Evangelista T, Behin A, Metay C, Stojkovic T
J Neurol 2024 Jul;271(7):4008-4018. Epub 2024 Mar 22 doi: 10.1007/s00415-024-12298-0. PMID: 38517523
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Dowling JJ, Moore SA, Kalimo H, Minassian BA
Acta Neuropathol 2015 Mar;129(3):383-90. Epub 2015 Feb 3 doi: 10.1007/s00401-015-1393-4. PMID: 25644398
Weihl CC, Iyadurai S, Baloh RH, Pittman SK, Schmidt RE, Lopate G, Pestronk A, Harms MB
Neuromuscul Disord 2015 Mar;25(3):199-206. Epub 2014 Dec 12 doi: 10.1016/j.nmd.2014.12.002. PMID: 25557463Free PMC Article
Kaneda D, Sugie K, Yamamoto A, Matsumoto H, Kato T, Nonaka I, Nishino I
Neurology 2003 Jul 8;61(1):128-31. doi: 10.1212/01.wnl.0000069605.00498.bd. PMID: 12847175

Diagnosis

Dwairi V, Giacobbe A, Zivkovic S, Lacomis D
J Clin Neuromuscul Dis 2024 Sep 1;26(1):12-15. doi: 10.1097/CND.0000000000000500. PMID: 39163157
Fernández-Eulate G, Alfieri G, Spinazzi M, Ackermann-Bonan I, Duval F, Solé G, Caillon F, Mercier S, Pereon Y, Magot A, Pegat A, Salort-Campana E, Chabrol B, Gorokhova S, Krahn M, Biancalana V, Evangelista T, Behin A, Metay C, Stojkovic T
J Neurol 2024 Jul;271(7):4008-4018. Epub 2024 Mar 22 doi: 10.1007/s00415-024-12298-0. PMID: 38517523
Rajeshwari M, Dhiman N, Chakrabarty B, Gulati S, Shamim U, Faruq M, Suri V, Sharma MC
Neurol India 2022 Jul-Aug;70(4):1643-1648. doi: 10.4103/0028-3886.355110. PMID: 36076674
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Mercier S, Magot A, Caillon F, Isidor B, David A, Ferrer X, Vital A, Coquet M, Penttilä S, Udd B, Mussini JM, Pereon Y
Muscle Nerve 2015 Oct;52(4):673-80. Epub 2015 Jun 3 doi: 10.1002/mus.24664. PMID: 25809233

Therapy

Ghosh PS, Swift D, Engel AG
Neurology 2013 Jun 4;80(23):e248-9. doi: 10.1212/WNL.0b013e318295d6f4. PMID: 23733558Free PMC Article

Prognosis

Rajeshwari M, Dhiman N, Chakrabarty B, Gulati S, Shamim U, Faruq M, Suri V, Sharma MC
Neurol India 2022 Jul-Aug;70(4):1643-1648. doi: 10.4103/0028-3886.355110. PMID: 36076674
Deneubourg C, Ramm M, Smith LJ, Baron O, Singh K, Byrne SC, Duchen MR, Gautel M, Eskelinen EL, Fanto M, Jungbluth H
Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Fernandes SA, Almeida CF, Souza LS, Lazar M, Onofre-Oliveira P, Yamamoto GL, Nogueira L, Tasaki LY, Cardoso RR, Pavanello RCM, Silva HCA, Ferrari MFR, Bigot A, Mouly V, Vainzof M
Dis Model Mech 2020 Jan 10;13(2) doi: 10.1242/dmm.041244. PMID: 31826868Free PMC Article
Munteanu I, Kalimo H, Saraste A, Nishino I, Minassian BA
Neuromuscul Disord 2017 Feb;27(2):185-187. Epub 2016 Oct 19 doi: 10.1016/j.nmd.2016.10.007. PMID: 27916343
Mercier S, Magot A, Caillon F, Isidor B, David A, Ferrer X, Vital A, Coquet M, Penttilä S, Udd B, Mussini JM, Pereon Y
Muscle Nerve 2015 Oct;52(4):673-80. Epub 2015 Jun 3 doi: 10.1002/mus.24664. PMID: 25809233

Clinical prediction guides

Fernández-Eulate G, Alfieri G, Spinazzi M, Ackermann-Bonan I, Duval F, Solé G, Caillon F, Mercier S, Pereon Y, Magot A, Pegat A, Salort-Campana E, Chabrol B, Gorokhova S, Krahn M, Biancalana V, Evangelista T, Behin A, Metay C, Stojkovic T
J Neurol 2024 Jul;271(7):4008-4018. Epub 2024 Mar 22 doi: 10.1007/s00415-024-12298-0. PMID: 38517523
Pegat A, Streichenberger N, Lacoste N, Hermier M, Menassa R, Coudert L, Theuriet J, Froissart R, Terrone S, Bouhour F, Michel-Calemard L, Schaeffer L, Jacquier A
Genes (Basel) 2022 Nov 29;13(12) doi: 10.3390/genes13122245. PMID: 36553512Free PMC Article
Fernandes SA, Almeida CF, Souza LS, Lazar M, Onofre-Oliveira P, Yamamoto GL, Nogueira L, Tasaki LY, Cardoso RR, Pavanello RCM, Silva HCA, Ferrari MFR, Bigot A, Mouly V, Vainzof M
Dis Model Mech 2020 Jan 10;13(2) doi: 10.1242/dmm.041244. PMID: 31826868Free PMC Article
Munteanu I, Ackerley CA, Mnatzakanian GN, Kissel JT, Minassian BA
Neurology 2005 Mar 8;64(5):927-8. doi: 10.1212/01.WNL.0000152884.11980.53. PMID: 15753448
Villard L, des Portes V, Levy N, Louboutin JP, Recan D, Coquet M, Chabrol B, Figarella-Branger D, Chelly J, Pellissier JF, Fontes M
Eur J Hum Genet 2000 Feb;8(2):125-9. doi: 10.1038/sj.ejhg.5200432. PMID: 10757644