Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies

G. Calcagni, R. Adorisio, S. Martinelli, G. Grutter, A. Baban, P. Versacci, M.C. Digilio, F. Drago, B.D. Gelb, M. Tartaglia, B. Marino

Research output: Contribution to journalArticle

Abstract

RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. © 2017 Elsevier Inc.
Original languageEnglish
Pages (from-to)225-235
Number of pages11
JournalHeart Failure Clinics
Volume14
Issue number2
DOIs
Publication statusPublished - 2018

Fingerprint

Hypertrophic Cardiomyopathy
Heart Failure
Congenital Heart Defects
Sirolimus
Mutation
Survival
Mortality
Genes
Therapeutics

Keywords

  • Congenital heart defect
  • Costello syndrome
  • Genotype-phenotype correlations
  • Hypertrophic cardiomyopathy
  • LEOPARD syndrome
  • Noonan syndrome
  • RAS signaling
  • RASopathies
  • mitogen activated protein kinase
  • Ras protein
  • clinical feature
  • gene mutation
  • genotype phenotype correlation
  • history
  • human
  • hypertrophic cardiomyopathy
  • molecular pathology
  • nonhuman
  • patient care
  • Review
  • genetic marker
  • genetic screening
  • genetics
  • metabolism
  • mutation
  • procedures
  • Cardiomyopathy, Hypertrophic
  • Genetic Markers
  • Genetic Testing
  • Humans
  • Mutation
  • ras Proteins

Cite this

Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies. / Calcagni, G.; Adorisio, R.; Martinelli, S.; Grutter, G.; Baban, A.; Versacci, P.; Digilio, M.C.; Drago, F.; Gelb, B.D.; Tartaglia, M.; Marino, B.

In: Heart Failure Clinics, Vol. 14, No. 2, 2018, p. 225-235.

Research output: Contribution to journalArticle

Calcagni, G, Adorisio, R, Martinelli, S, Grutter, G, Baban, A, Versacci, P, Digilio, MC, Drago, F, Gelb, BD, Tartaglia, M & Marino, B 2018, 'Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies', Heart Failure Clinics, vol. 14, no. 2, pp. 225-235. https://doi.org/10.1016/j.hfc.2017.12.005
Calcagni, G. ; Adorisio, R. ; Martinelli, S. ; Grutter, G. ; Baban, A. ; Versacci, P. ; Digilio, M.C. ; Drago, F. ; Gelb, B.D. ; Tartaglia, M. ; Marino, B. / Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies. In: Heart Failure Clinics. 2018 ; Vol. 14, No. 2. pp. 225-235.
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abstract = "RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. {\circledC} 2017 Elsevier Inc.",
keywords = "Congenital heart defect, Costello syndrome, Genotype-phenotype correlations, Hypertrophic cardiomyopathy, LEOPARD syndrome, Noonan syndrome, RAS signaling, RASopathies, mitogen activated protein kinase, Ras protein, clinical feature, gene mutation, genotype phenotype correlation, history, human, hypertrophic cardiomyopathy, molecular pathology, nonhuman, patient care, Review, genetic marker, genetic screening, genetics, metabolism, mutation, procedures, Cardiomyopathy, Hypertrophic, Genetic Markers, Genetic Testing, Humans, Mutation, ras Proteins",
author = "G. Calcagni and R. Adorisio and S. Martinelli and G. Grutter and A. Baban and P. Versacci and M.C. Digilio and F. Drago and B.D. Gelb and M. Tartaglia and B. Marino",
note = "Cited By :3 Export Date: 11 April 2019 Correspondence Address: Calcagni, G.; Department of Pediatric Cardiology and Cardiac Surgery, Bambino Ges{\`u} Children's Hospital and Research Institute, Piazza Sant'Onofrio 4, Italy; email: giulio.calcagni@opbg.net Chemicals/CAS: mitogen activated protein kinase, 142243-02-5; Genetic Markers; ras Proteins References: Elliott, P.M., Anastasakis, A., Borger, M.A., 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the diagnosis and management of hypertrophic cardiomyopathy of the European society of cardiology (ESC) (2014) Eur Heart J, 35 (39), pp. 2733-2779; Lipshultz, S.E., Sleeper, L.A., Towbin, J.A., The incidence of pediatric cardiomyopathy in two regions of the United States (2003) N Engl J Med, 348 (17), pp. 1647-1655; Colan, S.D., Lipshultz, S.E., Lowe, A.M., Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the pediatric cardiomyopathy registry (2007) Circulation, 115 (6), pp. 773-781; Nugent, A.W., Daubeney, P.E., Chondros, P., Clinical features and outcomes of childhood hypertrophic cardiomyopathy: results from a national population-based study (2005) Circulation, 112 (9), pp. 1332-1338; Moak, J.P., Kaski, J.P., Hypertrophic cardiomyopathy in children (2012) Heart, 98 (14), pp. 1044-1054; Roberts, A.E., Allanson, J.E., Tartaglia, M., Noonan syndrome (2013) Lancet, 381 (9863), pp. 333-342; Tartaglia, M., Gelb, B.D., Zenker, M., Noonan syndrome and clinically related disorders (2011) Best Pract Res Clin Endocrinol Metab, 25 (1), pp. 161-179; Tartaglia, M., Mehler, E.L., Goldberg, R., Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome (2001) Nat Genet, 29 (4), pp. 465-468; Tartaglia, M., Kalidas, K., Shaw, A., PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity (2002) Am J Hum Genet, 70 (6), pp. 1555-1563; Zenker, M., Buheitel, G., Rauch, R., Genotype-phenotype correlations in Noonan syndrome (2004) J Pediatr, 144 (3), pp. 368-374; Tartaglia, M., Niemeyer, C.M., Fragale, A., Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia (2003) Nat Genet, 34 (2), pp. 148-150; Tartaglia, M., Martinelli, S., Cazzaniga, G., Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia (2004) Blood, 104 (2), pp. 307-313; Tartaglia, M., Martinelli, S., Stella, L., Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease (2006) Am J Hum Genet, 78 (2), pp. 279-290; Strullu, M., Caye, A., Lachenaud, J., Juvenile myelomonocytic leukaemia and Noonan syndrome (2014) J Med Genet, 51 (10), pp. 689-697; Carta, C., Pantaleoni, F., Bocchinfuso, G., Germline missense mutations affecting KRAS isoform B are associated with a severe Noonan syndrome phenotype (2006) Am J Hum Genet, 79 (1), pp. 129-135; Schubbert, S., Zenker, M., Rowe, S.L., Germline KRAS mutations cause Noonan syndrome (2006) Nat Genet, 38 (3), pp. 331-336; 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TY - JOUR

T1 - Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies

AU - Calcagni, G.

AU - Adorisio, R.

AU - Martinelli, S.

AU - Grutter, G.

AU - Baban, A.

AU - Versacci, P.

AU - Digilio, M.C.

AU - Drago, F.

AU - Gelb, B.D.

AU - Tartaglia, M.

AU - Marino, B.

N1 - Cited By :3 Export Date: 11 April 2019 Correspondence Address: Calcagni, G.; Department of Pediatric Cardiology and Cardiac Surgery, Bambino Gesù Children's Hospital and Research Institute, Piazza Sant'Onofrio 4, Italy; email: giulio.calcagni@opbg.net Chemicals/CAS: mitogen activated protein kinase, 142243-02-5; Genetic Markers; ras Proteins References: Elliott, P.M., Anastasakis, A., Borger, M.A., 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the diagnosis and management of hypertrophic cardiomyopathy of the European society of cardiology (ESC) (2014) Eur Heart J, 35 (39), pp. 2733-2779; Lipshultz, S.E., Sleeper, L.A., Towbin, J.A., The incidence of pediatric cardiomyopathy in two regions of the United States (2003) N Engl J Med, 348 (17), pp. 1647-1655; Colan, S.D., Lipshultz, S.E., Lowe, A.M., Epidemiology and cause-specific outcome of hypertrophic cardiomyopathy in children: findings from the pediatric cardiomyopathy registry (2007) Circulation, 115 (6), pp. 773-781; Nugent, A.W., Daubeney, P.E., Chondros, P., Clinical features and outcomes of childhood hypertrophic cardiomyopathy: results from a national population-based study (2005) Circulation, 112 (9), pp. 1332-1338; Moak, J.P., Kaski, J.P., Hypertrophic cardiomyopathy in children (2012) Heart, 98 (14), pp. 1044-1054; Roberts, A.E., Allanson, J.E., Tartaglia, M., Noonan syndrome (2013) Lancet, 381 (9863), pp. 333-342; Tartaglia, M., Gelb, B.D., Zenker, M., Noonan syndrome and clinically related disorders (2011) Best Pract Res Clin Endocrinol Metab, 25 (1), pp. 161-179; Tartaglia, M., Mehler, E.L., Goldberg, R., Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome (2001) Nat Genet, 29 (4), pp. 465-468; Tartaglia, M., Kalidas, K., Shaw, A., PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity (2002) Am J Hum Genet, 70 (6), pp. 1555-1563; Zenker, M., Buheitel, G., Rauch, R., Genotype-phenotype correlations in Noonan syndrome (2004) J Pediatr, 144 (3), pp. 368-374; Tartaglia, M., Niemeyer, C.M., Fragale, A., Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia (2003) Nat Genet, 34 (2), pp. 148-150; Tartaglia, M., Martinelli, S., Cazzaniga, G., Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia (2004) Blood, 104 (2), pp. 307-313; Tartaglia, M., Martinelli, S., Stella, L., Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease (2006) Am J Hum Genet, 78 (2), pp. 279-290; Strullu, M., Caye, A., Lachenaud, J., Juvenile myelomonocytic leukaemia and Noonan syndrome (2014) J Med Genet, 51 (10), pp. 689-697; Carta, C., Pantaleoni, F., Bocchinfuso, G., Germline missense mutations affecting KRAS isoform B are associated with a severe Noonan syndrome phenotype (2006) Am J Hum Genet, 79 (1), pp. 129-135; Schubbert, S., Zenker, M., Rowe, S.L., Germline KRAS mutations cause Noonan syndrome (2006) Nat Genet, 38 (3), pp. 331-336; Tartaglia, M., Pennacchio, L.A., Zhao, C., Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome (2007) Nat Genet, 39 (1), pp. 75-79; Pandit, B., Sarkozy, A., Pennacchio, L.A., Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy (2007) Nat Genet, 39 (8), pp. 1007-1012; Razzaque, M.A., Nishizawa, T., Komoike, Y., Germline gain-of-function mutations in RAF1 cause Noonan syndrome (2007) Nat Genet, 39 (8), pp. 1013-1017; Nava, C., Hanna, N., Michot, C., Cardio-facio-cutaneous and Noonan syndromes due to mutations in the RAS/MAPK signalling pathway: genotype-phenotype relationships and overlap with Costello syndrome (2007) J Med Genet, 44 (12), pp. 763-771; Sarkozy, A., Carta, C., Moretti, S., Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum (2009) Hum Mutat, 30 (4), pp. 695-702; Cordeddu, V., Di Schiavi, E., Pennacchio, L.A., Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes noonan-like syndrome with loose anagen hair (2009) Nat Genet, 41 (9), pp. 1022-1026; 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PY - 2018

Y1 - 2018

N2 - RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. © 2017 Elsevier Inc.

AB - RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. © 2017 Elsevier Inc.

KW - Congenital heart defect

KW - Costello syndrome

KW - Genotype-phenotype correlations

KW - Hypertrophic cardiomyopathy

KW - LEOPARD syndrome

KW - Noonan syndrome

KW - RAS signaling

KW - RASopathies

KW - mitogen activated protein kinase

KW - Ras protein

KW - clinical feature

KW - gene mutation

KW - genotype phenotype correlation

KW - history

KW - human

KW - hypertrophic cardiomyopathy

KW - molecular pathology

KW - nonhuman

KW - patient care

KW - Review

KW - genetic marker

KW - genetic screening

KW - genetics

KW - metabolism

KW - mutation

KW - procedures

KW - Cardiomyopathy, Hypertrophic

KW - Genetic Markers

KW - Genetic Testing

KW - Humans

KW - Mutation

KW - ras Proteins

U2 - 10.1016/j.hfc.2017.12.005

DO - 10.1016/j.hfc.2017.12.005

M3 - Article

VL - 14

SP - 225

EP - 235

JO - Heart Failure Clinics

JF - Heart Failure Clinics

SN - 1551-7136

IS - 2

ER -