Atypical, severe hypertrophic cardiomyopathy in a newborn presenting Noonan syndrome harboring a recurrent heterozygous MRAS variant

Autor(es)

Pires, Lucas Vieira Lacerda ^[1] ; Bordim, Renata de Almeida ^[2] ; Maciel, Maria Beatriz Rabelo ^[2] ; Tanaka, Ana Cristina Sayuri ^[2] ; Yamamoto, Guilherme Lopes ^{[3, 1, 4]} ; Honjo, Rachel Sayuri ^[1] ; Kim, Chong Ae ^[1] ; Bertola, Debora Romeo ^{[3, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Crianca, Hosp Clin, Unidade Genet, Fac Med, Ave Dr Eneas de Carvalho Aguiar 647, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Crianca, Unidade Cardiopatias Congenitas, Hosp Clin, Fac Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biociencias, Sao Paulo - Brazil

^[4] DASA, GeneOne, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF MEDICAL GENETICS PART A; v. 185, n. 10, p. 3099-3103, OCT 2021.
• Citações Web of Science: 0

Resumo

Noonan syndrome (NS) is a Mendelian phenotype, member of a group of disorders sharing neurocardiofaciocutaneous involvement, known as RASopathies, caused by germline variants in genes coding for components of the RAS/MAPK signaling pathway. Recently, a novel gene of the RAS family (MRAS) was reported to be associated with NS in five children, all of them presenting, among the cardinal features of NS, the same cardiac finding, hypertrophic cardiomyopathy (HCM). We report on a 2-month-old infant boy also presenting this cardiac anomaly that evolved to a fatal outcome after a surgical myectomy. In addition, a thick walled left ventricle apical aneurysm, rarely described in NS, was also disclosed. Next-generation sequencing revealed a missense, previously reported variant in MRAS (p.Thr68Ile). This report reinforces the high frequency of HCM among individuals harboring MRAS variants, contrasting to the 20% overall prevalence of this cardiac anomaly in NS. Thus, these preliminary data suggest that variants in MRAS per se are high risk factors for the development of an early, severe HCM, mostly of them with left ventricle outflow tract obstruction, with poor prognosis. Because of the severity of the cardiac involvement, other clinical findings could not be addressed in detail. Therefore, long-term follow-up of these individuals and further descriptions are required to fully understand the complete phenotypic spectrum of NS associated with MRAS germline variants, including if these individuals present an increased risk for cancer. (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs