TY - JOUR
T1 - The heart in RASopathies
AU - Delogu, Angelica Bibiana
AU - Limongelli, Giuseppe
AU - Versacci, Paolo
AU - Adorisio, Rachele
AU - Kaski, Juan Pablo
AU - Blandino, Rita
AU - Maiolo, Stella
AU - Monda, Emanuele
AU - Putotto, Carolina
AU - De Rosa, Gabriella
AU - Chatfield, Kathryn C.
AU - Gelb, Bruce D.
AU - Calcagni, Giulio
N1 - Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2022/12
Y1 - 2022/12
N2 - The cardiovascular phenotype associated with RASopathies has expanded far beyond the original descriptions of pulmonary valve stenosis by Dr Jaqueline Noonan in 1968 and hypertrophic cardiomyopathy by Hirsch et al. in 1975. Because of the common underlying RAS/MAPK pathway dysregulation, RASopathy syndromes usually present with a typical spectrum of overlapping cardiovascular anomalies, although less common cardiac defects can occur. The identification of the causative genetic variants has enabled the recognition of specific correlations between genotype and cardiac phenotype. Characterization and understanding of genotype–phenotype associations is not only important for counseling a family of an infant with a new diagnosis of a RASopathy condition but is also critical for their clinical prognosis with respect to cardiac disease, neurodevelopment and other organ system involvement over the lifetime of the patient. This review will focus on the cardiac manifestations of the most common RASopathy syndromes, the relationship between cardiac defects and causal genetic variation, the contribution of cardiovascular abnormalities to morbidity and mortality and the most relevant follow-up issues for patients affected by RAS/MAPK pathway diseases, with respect to cardiac clinical outcomes and management, in children and in the adult population.
AB - The cardiovascular phenotype associated with RASopathies has expanded far beyond the original descriptions of pulmonary valve stenosis by Dr Jaqueline Noonan in 1968 and hypertrophic cardiomyopathy by Hirsch et al. in 1975. Because of the common underlying RAS/MAPK pathway dysregulation, RASopathy syndromes usually present with a typical spectrum of overlapping cardiovascular anomalies, although less common cardiac defects can occur. The identification of the causative genetic variants has enabled the recognition of specific correlations between genotype and cardiac phenotype. Characterization and understanding of genotype–phenotype associations is not only important for counseling a family of an infant with a new diagnosis of a RASopathy condition but is also critical for their clinical prognosis with respect to cardiac disease, neurodevelopment and other organ system involvement over the lifetime of the patient. This review will focus on the cardiac manifestations of the most common RASopathy syndromes, the relationship between cardiac defects and causal genetic variation, the contribution of cardiovascular abnormalities to morbidity and mortality and the most relevant follow-up issues for patients affected by RAS/MAPK pathway diseases, with respect to cardiac clinical outcomes and management, in children and in the adult population.
KW - Costello syndrome
KW - Noonan syndrome
KW - Noonan syndrome with multiple lentigines
KW - RASopathy
KW - cardio-facio-cutaneous syndrome
KW - congenital heart disease
UR - http://www.scopus.com/inward/record.url?scp=85143440443&partnerID=8YFLogxK
U2 - 10.1002/ajmg.c.32014
DO - 10.1002/ajmg.c.32014
M3 - Review article
C2 - 36408797
AN - SCOPUS:85143440443
SN - 1552-4868
VL - 190
SP - 440
EP - 451
JO - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
JF - American Journal of Medical Genetics, Part C: Seminars in Medical Genetics
IS - 4
ER -