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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
Areflexia of lower limbs
MedGen UID:
347285
Concept ID:
C1856694
Finding
Inability to elicit tendon reflexes in the lower limbs.
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.
Falls
MedGen UID:
39084
Concept ID:
C0085639
Finding
A sudden movement downward, usually resulting in injury.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
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.
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.
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.
Hypocalcemia
MedGen UID:
5705
Concept ID:
C0020598
Disease or Syndrome
An abnormally decreased calcium concentration in the blood.
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.
Miosis
MedGen UID:
6409
Concept ID:
C0026205
Disease or Syndrome
Abnormal (non-physiological) constriction of the pupil.

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
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
Naddaf E, Milone M, Kansagra A, Buadi F, Kourelis T
Neurology 2019 Jul 16;93(3):e298-e305. Epub 2019 Jun 5 doi: 10.1212/WNL.0000000000007777. PMID: 31167932

Recent clinical studies

Etiology

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
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
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

Diagnosis

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
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
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

Therapy

van Kleef ESB, Langer D, van Engelen BGM, Ottenheijm CAC, Voermans NC, Doorduin J
J Neuromuscul Dis 2023;10(5):825-834. doi: 10.3233/JND-221665. PMID: 37458044
Vita G, Vita GL, Musumeci O, Rodolico C, Messina S
Neurol Sci 2019 Apr;40(4):671-681. Epub 2019 Feb 25 doi: 10.1007/s10072-019-03764-z. PMID: 30805745
Elahi B, Laughlin RS, Litchy WJ, Milone M, Liewluck T
Muscle Nerve 2019 Apr;59(4):475-478. Epub 2019 Jan 6 doi: 10.1002/mus.26393. PMID: 30536954
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
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

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
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
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
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 Jul 13;2:31. doi: 10.1186/1750-1172-2-31. PMID: 17631035Free PMC Article

Clinical prediction guides

du Fay de Lavallaz J, Prepoudis A, Wendebourg MJ, Kesenheimer E, Kyburz D, Daikeler T, Haaf P, Wanschitz J, Löscher WN, Schreiner B, Katan M, Jung HH, Maurer B, Hammerer-Lercher A, Mayr A, Gualandro DM, Acket A, Puelacher C, Boeddinghaus J, Nestelberger T, Lopez-Ayala P, Glarner N, Shrestha S, Manka R, Gawinecka J, Piscuoglio S, Gallon J, Wiedemann S, Sinnreich M, Mueller C; BASEL XII Investigators
Circulation 2022 Jun 14;145(24):1764-1779. Epub 2022 Apr 7 doi: 10.1161/CIRCULATIONAHA.121.058489. PMID: 35389756Free PMC Article
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
Lacruz RS, Feske S
Ann N Y Acad Sci 2015 Nov;1356(1):45-79. Epub 2015 Oct 15 doi: 10.1111/nyas.12938. PMID: 26469693Free PMC Article
Chen T, Pu C, Wang Q, Liu J, Mao Y, Shi Q
Neurol Sci 2015 May;36(5):735-41. Epub 2014 Dec 12 doi: 10.1007/s10072-014-2028-6. PMID: 25501959
Jeannet PY, Bassez G, Eymard B, Laforêt P, Urtizberea JA, Rouche A, Guicheney P, Fardeau M, Romero NB
Neurology 2004 May 11;62(9):1484-90. doi: 10.1212/01.wnl.0000124388.67003.56. PMID: 15136669

Recent systematic reviews

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: 37483025

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