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Myopathy, tubular aggregate, 2(TAM2)

MedGen UID:
862994
•Concept ID:
C4014557
•
Disease or Syndrome
Synonym: TAM2
 
Gene (location): ORAI1 (12q24.31)
 
Monarch Initiative: MONDO:0014383
OMIM®: 615883

Definition

Any tubular aggregate myopathy in which the cause of the disease is a mutation in the ORAI1 gene. [from MONDO]

Clinical features

From HPO
Ankle flexion contracture
MedGen UID:
332440
•Concept ID:
C1837407
•
Anatomical Abnormality
See: Feature record | Search on this feature
Areflexia of lower limbs
MedGen UID:
347285
•Concept ID:
C1856694
•
Finding
Inability to elicit tendon reflexes in the lower limbs.
See: Feature record | Search on this feature
Foot dorsiflexor weakness
MedGen UID:
356163
•Concept ID:
C1866141
•
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
See: Feature record | Search on this feature
Falls
MedGen UID:
39084
•Concept ID:
C0085639
•
Finding
A sudden movement downward, usually resulting in injury.
See: Feature record | Search on this feature
Muscle weakness
MedGen UID:
57735
•Concept ID:
C0151786
•
Finding
Reduced strength of muscles.
See: Feature record | Search on this feature
Proximal muscle weakness
MedGen UID:
113169
•Concept ID:
C0221629
•
Finding
A lack of strength of the proximal muscles.
See: Feature record | Search on this feature
Neck muscle weakness
MedGen UID:
66808
•Concept ID:
C0240479
•
Finding
Decreased strength of the neck musculature.
See: Feature record | Search on this feature
Generalized muscle weakness
MedGen UID:
155433
•Concept ID:
C0746674
•
Sign or Symptom
Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature.
See: Feature record | Search on this feature
Spinal rigidity
MedGen UID:
346721
•Concept ID:
C1858025
•
Finding
Reduced ability to move the vertebral column with a resulting limitation of neck and trunk flexion.
See: Feature record | Search on this feature
Hypocalcemia
MedGen UID:
5705
•Concept ID:
C0020598
•
Disease or Syndrome
An abnormally decreased calcium concentration in the blood.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Miosis
MedGen UID:
6409
•Concept ID:
C0026205
•
Disease or Syndrome
Abnormal (non-physiological) constriction of the pupil.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances.
Gómez-Oca R, Cowling BS, Laporte J
Int J Mol Sci 2021 Oct 21;22(21) doi: 10.3390/ijms222111377. PMID: 34768808Free PMC Article
Tubular aggregate myopathy and Stormorken syndrome: Mutation spectrum and genotype/phenotype correlation.
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
Clinical utility gene card for: Central core disease.
Lillis S, Abbs S, Mueller CR, Muntoni F, Jungbluth H
Eur J Hum Genet 2012 Feb;20(2) Epub 2011 Oct 12 doi: 10.1038/ejhg.2011.179. PMID: 21989361Free PMC Article

Recent clinical studies

Etiology

Congenital myopathies: an update.
Claeys KG
Dev Med Child Neurol 2020 Mar;62(3):297-302. Epub 2019 Oct 2 doi: 10.1111/dmcn.14365. PMID: 31578728
Congenital Muscular Dystrophy and Congenital Myopathy.
Butterfield RJ
Continuum (Minneap Minn) 2019 Dec;25(6):1640-1661. doi: 10.1212/CON.0000000000000792. PMID: 31794464
Nemaline myopathies: a current view.
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
Centronuclear myopathies under attack: A plethora of therapeutic targets.
Tasfaout H, Cowling BS, Laporte J
J Neuromuscul Dis 2018;5(4):387-406. doi: 10.3233/JND-180309. PMID: 30103348Free PMC Article
Congenital myopathies.
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

Congenital myopathies: an update.
Claeys KG
Dev Med Child Neurol 2020 Mar;62(3):297-302. Epub 2019 Oct 2 doi: 10.1111/dmcn.14365. PMID: 31578728
Congenital Muscular Dystrophy and Congenital Myopathy.
Butterfield RJ
Continuum (Minneap Minn) 2019 Dec;25(6):1640-1661. doi: 10.1212/CON.0000000000000792. PMID: 31794464
Nemaline myopathies: a current view.
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
Congenital fiber-type disproportion.
Clarke NF
Semin Pediatr Neurol 2011 Dec;18(4):264-71. doi: 10.1016/j.spen.2011.10.008. PMID: 22172422
Congenital myopathies.
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

Therapy

Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial.
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
Indications for Tube Feeding in Adults with Muscular Disorders: A Scoping Review.
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
Allele-specific silencing therapy for Dynamin 2-related dominant centronuclear myopathy.
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
Respiratory motor function in individuals with centronuclear myopathies.
Smith BK, Renno MS, Green MM, Sexton TM, Lawson LA, Martin AD, Corti M, Byrne BJ
Muscle Nerve 2016 Feb;53(2):214-21. Epub 2015 Dec 29 doi: 10.1002/mus.24899. PMID: 26351754Free PMC Article
Malignant hyperthermia.
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

Imaging-based evaluation of pathogenicity by novel DNM2 variants associated with centronuclear myopathy.
Fujise K, Okubo M, Abe T, Yamada H, Takei K, Nishino I, Takeda T, Noguchi S
Hum Mutat 2022 Feb;43(2):169-179. Epub 2021 Dec 19 doi: 10.1002/humu.24307. PMID: 34837441
Nemaline myopathies: a current view.
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
Centronuclear (myotubular) myopathy.
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
Multi-minicore Disease.
Jungbluth H
Orphanet J Rare Dis 2007 Jul 13;2:31. doi: 10.1186/1750-1172-2-31. PMID: 17631035Free PMC Article
Central core disease.
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

Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial.
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
Natural history study and statistical modeling of disease progression in a preclinical model of myotubular myopathy.
Buono S, Monseur A, Menuet A, Robé A, Koch C, Laporte J, Thielemans L, Depla M, Cowling BS
Dis Model Mech 2022 Jul 1;15(7) Epub 2022 Jul 25 doi: 10.1242/dmm.049284. PMID: 35642830Free PMC Article
Derivation of NEM2 affected human embryonic stem cell line Genea080.
Dumevska B, McKernan R, Goel D, Schmidt U
Stem Cell Res 2016 Mar;16(2):443-5. Epub 2016 Feb 11 doi: 10.1016/j.scr.2016.02.016. PMID: 27346011
Derivation of NEM2 affected human embryonic stem cell line Genea079.
Dumevska B, McKernan R, Goel D, Schmidt U
Stem Cell Res 2016 Mar;16(2):440-2. Epub 2016 Feb 11 doi: 10.1016/j.scr.2016.02.015. PMID: 27346010
Derivation of NEM2 affected human embryonic stem cell line Genea078.
Dumevska B, Main H, McKernan R, Goel D, Schmidt U
Stem Cell Res 2016 Mar;16(2):427-9. Epub 2016 Feb 3 doi: 10.1016/j.scr.2016.02.004. PMID: 27346006

Recent systematic reviews

Maternal health and obstetric complications of genetic neuromuscular disorders in pregnancy: A systematic review.
Ahmed HS, Teli A, Khullar K, Deepak BL
Eur J Obstet Gynecol Reprod Biol 2025 Jan;304:152-170. Epub 2024 Nov 28 doi: 10.1016/j.ejogrb.2024.11.046. PMID: 39616806
KLHL40-Related Myopathy: A Systematic Review and Insight into a Follow-up Biomarker via a New Case Report.
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

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