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Hypertrophic cardiomyopathy 6(CMH6)

MedGen UID:
331466
Concept ID:
C1833236
Disease or Syndrome
Synonym: Cardiomyopathy, Familial Hypertrophic, 6
 
Gene (location): PRKAG2 (7q36.1)
 
Monarch Initiative: MONDO:0010946
OMIM®: 600858

Definition

Mutations in the PRKAG2 gene (602743) give rise to a moderate, essentially heart-specific, nonlysosomal glycogenosis with clinical onset typically in late adolescence or in the third decade of life, ventricular pre-excitation predisposing to supraventricular arrhythmias, mild to severe cardiac hypertrophy, enhanced risk of sudden cardiac death in midlife, and autosomal dominant inheritance with full penetrance (summary by Burwinkel et al., 2005). [from OMIM]

Clinical features

From HPO
Chest pain
MedGen UID:
2992
Concept ID:
C0008031
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the chest.
Atrial fibrillation
MedGen UID:
445
Concept ID:
C0004238
Finding
An atrial arrhythmia characterized by disorganized atrial activity without discrete P waves on the surface EKG, but instead by an undulating baseline or more sharply circumscribed atrial deflections of varying amplitude an frequency ranging from 350 to 600 per minute.
Atrioventricular block
MedGen UID:
13956
Concept ID:
C0004245
Disease or Syndrome
Delayed or lack of conduction of atrial depolarizations through the atrioventricular node to the ventricles.
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Left bundle branch block
MedGen UID:
7286
Concept ID:
C0023211
Disease or Syndrome
A conduction block of the left branch of the bundle of His. This manifests as a generalized disturbance of QRS morphology on EKG.
Palpitations
MedGen UID:
14579
Concept ID:
C0030252
Finding
A sensation that the heart is pounding or racing, which is a non-specific sign but may be a manifestation of arrhythmia.
Syncope
MedGen UID:
21443
Concept ID:
C0039070
Sign or Symptom
A transient loss of consciousness (i.e., characterized by a rapid onset, a short duration, and a spontaneous and complete recovery) due to cerebral hypoperfusion.
Wolff-Parkinson-White pattern
MedGen UID:
12162
Concept ID:
C0043202
Disease or Syndrome
Wolff-Parkinson-White syndrome (WPW) is characterized by paroxysmal supraventricular tachycardia that may produce presyncope, syncope, and shortness of breath and cause sudden death. Electrocardiography shows a short PR interval with a widened QRS complex or an abnormal initial QRS vector (delta wave), diagnostic of ventricular preexcitation (summary by Gollob et al., 2001).
Sinus bradycardia
MedGen UID:
39316
Concept ID:
C0085610
Pathologic Function
Bradycardia related to a mean resting sinus rate of less than 50 beats per minute.
Asymmetric septal hypertrophy
MedGen UID:
104705
Concept ID:
C0205700
Disease or Syndrome
Hypertrophic cardiomyopathy with an asymmetrical pattern of hypertrophy, with a predilection for the interventricular septum and myocyte disarray.
Prolonged QRS complex
MedGen UID:
489828
Concept ID:
C0235475
Finding
Increased time for the complex comprised of the Q wave, R wave, and S wave as measured by the electrocardiogram (EKG).. In adults, normal values are 0.06 - 0.10 sec.
Shortened PR interval
MedGen UID:
105466
Concept ID:
C0520878
Finding
Reduced time for the PR interval (beginning of the P wave to the beginning of the QRS complex). In adults, normal values are 120 to 200 ms long.
Ventricular preexcitation
MedGen UID:
107848
Concept ID:
C0559106
Disease or Syndrome
An abnormality in which the cardiac ventricles depolarize too early as a result of an abnormality of cardiac conduction pathways such as an accessory pathway.
Myofiber disarray
MedGen UID:
1615672
Concept ID:
C3671015
Finding
A nonparallel arrangement of cardiac myocytes.
Aborted sudden cardiac death
MedGen UID:
1632505
Concept ID:
C4703449
Finding
Cardiac arrest that would have led to rapid and unexpected death had an intervention not taken place to prevent it.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Gruner C, Ivanov J, Care M, Williams L, Moravsky G, Yang H, Laczay B, Siminovitch K, Woo A, Rakowski H
Circ Cardiovasc Genet 2013 Feb;6(1):19-26. Epub 2012 Dec 13 doi: 10.1161/CIRCGENETICS.112.963363. PMID: 23239831

Curated

Pinto YM, Wilde AA, van Rijsingen IA, Christiaans I, Deprez RH, Elliott PM
Eur J Hum Genet 2011 Aug;19(8) Epub 2011 Jan 26 doi: 10.1038/ejhg.2010.243. PMID: 21267010Free PMC Article

Recent clinical studies

Etiology

Abbasi M, Ong KC, Newman DB, Dearani JA, Schaff HV, Geske JB
J Am Soc Echocardiogr 2024 Jun;37(6):613-625. Epub 2024 Feb 28 doi: 10.1016/j.echo.2024.02.010. PMID: 38428652
Geske JB, Ommen SR, Gersh BJ
JACC Heart Fail 2018 May;6(5):364-375. Epub 2018 Apr 11 doi: 10.1016/j.jchf.2018.02.010. PMID: 29655825
Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM
Heart 2015 Feb;101(4):294-301. Epub 2014 Oct 28 doi: 10.1136/heartjnl-2014-306387. PMID: 25351510Free PMC Article
Berge KE, Leren TP
Clin Genet 2014 Oct;86(4):355-60. Epub 2013 Oct 23 doi: 10.1111/cge.12286. PMID: 24111713
Ho CY
Heart Fail Clin 2010 Apr;6(2):141-59. doi: 10.1016/j.hfc.2009.12.001. PMID: 20347784Free PMC Article

Diagnosis

Zhang Y, Adamo M, Zou C, Porcari A, Tomasoni D, Rossi M, Merlo M, Liu H, Wang J, Zhou P, Metra M, Sinagra G, Zhang J
J Cardiovasc Med (Hagerstown) 2024 Jun 1;25(6):399-419. Epub 2024 Apr 26 doi: 10.2459/JCM.0000000000001616. PMID: 38625835Free PMC Article
Abbasi M, Ong KC, Newman DB, Dearani JA, Schaff HV, Geske JB
J Am Soc Echocardiogr 2024 Jun;37(6):613-625. Epub 2024 Feb 28 doi: 10.1016/j.echo.2024.02.010. PMID: 38428652
Geske JB, Ommen SR, Gersh BJ
JACC Heart Fail 2018 May;6(5):364-375. Epub 2018 Apr 11 doi: 10.1016/j.jchf.2018.02.010. PMID: 29655825
Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM
Heart 2015 Feb;101(4):294-301. Epub 2014 Oct 28 doi: 10.1136/heartjnl-2014-306387. PMID: 25351510Free PMC Article
Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M; EUROGENE Heart Failure Project
Circulation 2003 May 6;107(17):2227-32. Epub 2003 Apr 21 doi: 10.1161/01.CIR.0000066323.15244.54. PMID: 12707239

Therapy

Rossano JW, Canter C, Wolf CM, Papez A, Gambra M, Bryant RM, Alejos J, McCulloch M, Sarquella Brugada G, Bock MJ, Jeewa A, Pearce FB, Desai MY, Favatella N, Javidialsaadi A, Phung V, Rano T, Zhu L, Dyme JL, Mital S; SCOUT-HCM Investigators
N Engl J Med 2026 Jul 23;395(4):362-373. Epub 2026 Mar 29 doi: 10.1056/NEJMoa2601103. PMID: 41910394
Desai MY, Owens AT, Abraham T, Olivotto I, Garcia-Pavia P, Lopes RD, Elliott P, Fernandes F, Verheyen N, Maier L, Meder B, Azevedo O, Kitaoka H, Wolski K, Wang Q, Jaber W, Mitchell L, Myers J, Rano T, Gong Z, Zhong Y, Carter-Bonanza S, Florea V, Aronson R, Nissen SE; ODYSSEY-HCM Investigators
N Engl J Med 2025 Sep 11;393(10):961-972. Epub 2025 Aug 30 doi: 10.1056/NEJMoa2505927. PMID: 40888717
Davis BJ, Volk H, Nguyen O, Kamna D, Chen H, Barriales-Villa R, Garcia-Pavia P, Olivotto I, Owens AT, Coats CJ, Abraham TP, Solomon SD, Maron MS, Masri A
J Am Heart Assoc 2025 Mar 18;14(6):e038758. Epub 2025 Mar 7 doi: 10.1161/JAHA.124.038758. PMID: 40055855Free PMC Article
Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, Saberi S, Lakdawala NK, Wheeler MT, Owens A, Kubanek M, Wojakowski W, Jensen MK, Gimeno-Blanes J, Afshar K, Myers J, Hegde SM, Solomon SD, Sehnert AJ, Zhang D, Li W, Bhattacharya M, Edelberg JM, Waldman CB, Lester SJ, Wang A, Ho CY, Jacoby D; EXPLORER-HCM study investigators
Lancet 2020 Sep 12;396(10253):759-769. Epub 2020 Aug 29 doi: 10.1016/S0140-6736(20)31792-X. PMID: 32871100
Geske JB, Ommen SR, Gersh BJ
JACC Heart Fail 2018 May;6(5):364-375. Epub 2018 Apr 11 doi: 10.1016/j.jchf.2018.02.010. PMID: 29655825

Prognosis

Groussin P, Dezecot M, Decaudin D, Pavin D, Ninni S, Klein C, Ollitrault P, Champ Rigot L, Font J, Da Costa A, Sellal JM, Hammache N, Salaun A, Guenancia C, Mabo P, Benali K, Martins R
JACC Clin Electrophysiol 2025 Nov;11(11):2323-2334. Epub 2025 Aug 20 doi: 10.1016/j.jacep.2025.06.035. PMID: 40838922
Saberi S, Abraham TP, Choudhury L, Barriales-Villa R, Elliott PM, Nassif ME, Oreziak A, Owens AT, Tower-Rader A, Rader F, Garcia-Pavia P, Olivotto I, Coats CJ, Fifer MA, Sherrid MV, Solomon SD, Watkins H, Heitner SB, Jacoby DL, Kupfer S, Malik FI, Melloni C, Meng L, Wei J, Maron MS, Masri A; FOREST-HCM Steering Committee and Investigators
JACC Heart Fail 2025 Aug;13(8):102496. Epub 2025 Jun 19 doi: 10.1016/j.jchf.2025.03.040. PMID: 40540987
Amano M, Kitaoka H, Yoshikawa Y, Sakata Y, Dohi K, Tokita Y, Kato T, Matsushima S, Kitai T, Okada A, Furukawa Y, Tamura T, Hayashida A, Abe H, Ando K, Yuda S, Inoko M, Kadota K, Abe Y, Iwakura K, Kitamura T, Masuda J, Ohara T, Omura T, Tanigawa T, Nakamura K, Nishimura K, Izumi C; REVEAL-HCM Investigators
JACC Heart Fail 2025 Jun;13(6):1014-1026. Epub 2025 Mar 12 doi: 10.1016/j.jchf.2024.12.006. PMID: 40088231
Ha KE, Choi KU, Lee HJ, Gwak SY, Kim K, Cho I, Hong GR, Ha JW, Shim CY
ESC Heart Fail 2023 Oct;10(5):2939-2947. Epub 2023 Jul 22 doi: 10.1002/ehf2.14481. PMID: 37483012Free PMC Article
Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, Cirino AL, Fox JC, Lakdawala NK, Ware JS, Caleshu CA, Helms AS, Colan SD, Girolami F, Cecchi F, Seidman CE, Sajeev G, Signorovitch J, Green EM, Olivotto I
Circulation 2018 Oct 2;138(14):1387-1398. Epub 2018 Aug 23 doi: 10.1161/CIRCULATIONAHA.117.033200. PMID: 30297972Free PMC Article

Clinical prediction guides

Zhao K, Zhu Y, Chen X, Yang S, Yan W, Yang K, Song Y, Cui C, Xu X, Zhu Q, Cui ZX, Yin G, Cheng H, Lu M, Liang D, Shi K, Zhao L, Liu H, Zhang J, Chen L, Prasad SK, Zhao S, Zheng H
JACC Cardiovasc Imaging 2024 Aug;17(8):880-893. Epub 2024 Jul 10 doi: 10.1016/j.jcmg.2024.04.013. PMID: 39001729
Hughes RK, Shiwani H, Rosmini S, Augusto JB, Burke L, Jiang Y, Pierce I, Joy G, Castelletti S, Orini M, Kellman P, Xue H, Lopes LR, Mohiddin S, Treibel T, Manisty C, Captur G, Davies R, Moon JC
JACC Cardiovasc Imaging 2024 May;17(5):501-512. Epub 2023 Oct 11 doi: 10.1016/j.jcmg.2023.07.012. PMID: 37831014
Kiaos A, Daskalopoulos GN, Kamperidis V, Ziakas A, Efthimiadis G, Karamitsos TD
JACC Cardiovasc Imaging 2024 May;17(5):489-497. Epub 2023 Aug 23 doi: 10.1016/j.jcmg.2023.07.005. PMID: 37632503
Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM
Heart 2015 Feb;101(4):294-301. Epub 2014 Oct 28 doi: 10.1136/heartjnl-2014-306387. PMID: 25351510Free PMC Article
Bos JM, Will ML, Gersh BJ, Kruisselbrink TM, Ommen SR, Ackerman MJ
Mayo Clin Proc 2014 Jun;89(6):727-37. Epub 2014 May 1 doi: 10.1016/j.mayocp.2014.01.025. PMID: 24793961Free PMC Article

Recent systematic reviews

Reynolds G, Gazzin A, Carli D, Massuras S, Cardaropoli S, Luca M, Defilippi B, Tartaglia M, Ferrero GB, Mussa A
Int J Mol Sci 2025 Apr 9;26(8) doi: 10.3390/ijms26083515. PMID: 40332000Free PMC Article
Davis BJ, Volk H, Nguyen O, Kamna D, Chen H, Barriales-Villa R, Garcia-Pavia P, Olivotto I, Owens AT, Coats CJ, Abraham TP, Solomon SD, Maron MS, Masri A
J Am Heart Assoc 2025 Mar 18;14(6):e038758. Epub 2025 Mar 7 doi: 10.1161/JAHA.124.038758. PMID: 40055855Free PMC Article
Asatryan B, Rieder M, Murray B, Muller SA, Tichnell C, Gasperetti A, Carrick RT, Joseph E, Leung DG, Te Riele ASJM, Zimmerman SL, Calkins H, James CA, Barth AS
Circ Genom Precis Med 2025 Apr;18(2):e004878. Epub 2025 Feb 19 doi: 10.1161/CIRCGEN.124.004878. PMID: 39968648Free PMC Article
Kiaos A, Daskalopoulos GN, Kamperidis V, Ziakas A, Efthimiadis G, Karamitsos TD
JACC Cardiovasc Imaging 2024 May;17(5):489-497. Epub 2023 Aug 23 doi: 10.1016/j.jcmg.2023.07.005. PMID: 37632503
Aimo A, Merlo M, Porcari A, Georgiopoulos G, Pagura L, Vergaro G, Sinagra G, Emdin M, Rapezzi C
Eur J Heart Fail 2022 Dec;24(12):2342-2351. Epub 2022 May 16 doi: 10.1002/ejhf.2532. PMID: 35509173Free PMC Article

Supplemental Content

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      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, 2011
      Clinical utility gene card for: hypertrophic cardiomyopathy (type 1-14).

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