Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients

Mark D. Levin, Sulagna C. Saitta, Karen W. Gripp, Tara L. Wenger, Jaya Ganesh, Jennifer M. Kalish, Michael R. Epstein, Rosemarie Smith, Richard J. Czosek, Stephanie Ware, Paula Goldenberg, Angela Myers, Kathryn C. Chatfield, Matthew J. Gillespie, Elaine H. Zackai, Angela E. Lin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Multifocal atrial tachycardia (MAT) has a well-known association with Costello syndrome, but is rarely described with related RAS/MAPK pathway disorders (RASopathies). We report 11 patients with RASopathies (Costello, Noonan, and Noonan syndrome with multiple lentigines [formerly LEOPARD syndrome]) and nonreentrant atrial tachycardias (MAT and ectopic atrial tachycardia) demonstrating overlap in cardiac arrhythmia phenotype. Similar overlap is seen in RASopathies with respect to skeletal, musculoskeletal and cutaneous abnormalities, dysmorphic facial features, and neurodevelopmental deficits. Nonreentrant atrial tachycardias may cause cardiac compromise if sinus rhythm is not restored expeditiously. Typical first-line supraventricular tachycardia anti-arrhythmics (propranolol and digoxin) were generally not effective in restoring or maintaining sinus rhythm in this cohort, while flecainide or amiodarone alone or in concert with propranolol were effective anti-arrhythmic agents for acute and chronic use. Atrial tachycardia resolved in all patients. However, a 4-month-old boy from the cohort was found asystolic (with concurrent cellulitis) and a second patient underwent cardiac transplant for heart failure complicated by recalcitrant atrial arrhythmia. While propranolol alone frequently failed to convert or maintain sinus rhythm, fleccainide or amiodarone, occasionally in combination with propranolol, was effective for RASopathy patient treatment for nonreentrant atrial arrhythmia. Our analysis shows that RASopathy patients may have nonreentrant atrial tachycardia with and without associated cardiac hypertrophy. While nonreentrant arrhythmia has been traditionally associated with Costello syndrome, this work provides an expanded view of RASopathy cardiac arrhythmia phenotype as we demonstrate mutant proteins throughout this signaling pathway can also give rise to ectopic and/or MAT.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part A
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Hypertrophic Cardiomyopathy
Tachycardia
Cardiac Arrhythmias
Propranolol
Costello Syndrome
LEOPARD Syndrome
Amiodarone
Anti-Arrhythmia Agents
Musculoskeletal Abnormalities
Ectopic Atrial Tachycardia
Skin Abnormalities
Flecainide
Phenotype
Supraventricular Tachycardia
Cellulitis
Digoxin
Cardiomegaly
Mutant Proteins
Heart Failure
Transplants

Keywords

  • Calcium
  • Costello syndrome
  • Ectopic atrial tachycardia
  • Multifocal atrial tachycardia
  • Noonan syndrome
  • Noonan syndrome with multiple lentigines
  • RAS/MAPK signaling pathway

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Levin, M. D., Saitta, S. C., Gripp, K. W., Wenger, T. L., Ganesh, J., Kalish, J. M., ... Lin, A. E. (Accepted/In press). Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients. American Journal of Medical Genetics, Part A. https://doi.org/10.1002/ajmg.a.38854

Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients. / Levin, Mark D.; Saitta, Sulagna C.; Gripp, Karen W.; Wenger, Tara L.; Ganesh, Jaya; Kalish, Jennifer M.; Epstein, Michael R.; Smith, Rosemarie; Czosek, Richard J.; Ware, Stephanie; Goldenberg, Paula; Myers, Angela; Chatfield, Kathryn C.; Gillespie, Matthew J.; Zackai, Elaine H.; Lin, Angela E.

In: American Journal of Medical Genetics, Part A, 01.01.2018.

Research output: Contribution to journalArticle

Levin, MD, Saitta, SC, Gripp, KW, Wenger, TL, Ganesh, J, Kalish, JM, Epstein, MR, Smith, R, Czosek, RJ, Ware, S, Goldenberg, P, Myers, A, Chatfield, KC, Gillespie, MJ, Zackai, EH & Lin, AE 2018, 'Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients', American Journal of Medical Genetics, Part A. https://doi.org/10.1002/ajmg.a.38854
Levin, Mark D. ; Saitta, Sulagna C. ; Gripp, Karen W. ; Wenger, Tara L. ; Ganesh, Jaya ; Kalish, Jennifer M. ; Epstein, Michael R. ; Smith, Rosemarie ; Czosek, Richard J. ; Ware, Stephanie ; Goldenberg, Paula ; Myers, Angela ; Chatfield, Kathryn C. ; Gillespie, Matthew J. ; Zackai, Elaine H. ; Lin, Angela E. / Nonreentrant atrial tachycardia occurs independently of hypertrophic cardiomyopathy in RASopathy patients. In: American Journal of Medical Genetics, Part A. 2018.
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AU - Saitta, Sulagna C.

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AU - Ganesh, Jaya

AU - Kalish, Jennifer M.

AU - Epstein, Michael R.

AU - Smith, Rosemarie

AU - Czosek, Richard J.

AU - Ware, Stephanie

AU - Goldenberg, Paula

AU - Myers, Angela

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