Cardiovascular disease in Noonan syndrome

Pierpont, Mary Ella M; Digilio, María Cristina

doi:10.1097/mop.0000000000000669

Cited by 46 publications

(45 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All patients had a clinical diagnosis of NS or NSML. Patients with a negative or unknown mutation status were included, as the sensitivity of genetic testing is approximated to be only 75%‐90%, and new genes associated with RASopathy phenotypes are still being discovered . All but three patients had a confirmed genetic mutation associated with NS or NSML.…”

Section: Discussionmentioning

confidence: 99%

“…The patient reported by Al‐Rahawan was initially suspected to have CS, but eventually diagnosed with CFC post‐mortem with detection of a MEK1 / MAP2K1 mutation . There are occasional published reports of MAP2K1 mutations in patients with a NS phenotype . This emphasizes the well‐known phenotypic overlap between the RASopathies that may lead to misclassification, particularly in very young children.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with a negative or unknown mutation status were included, as the sensitivity of genetic testing is approximated to be only 75%-90%, and new genes associated with RASopathy phenotypes are still being discovered. 6 All but three patients had a confirmed genetic mutation associated with NS or NSML. The distinction between NS and NSML is important in that the associated genetic alteration has very different effects on the PTPN11 gene product, the Shp2 (src homology region 2-domain phosphatase-2) protein.…”

Section: Other Comorbiditiesmentioning

confidence: 93%

“…It is also now appreciated that HCM occurs in 20% of children with NS, typically presenting in infancy . HCM is known to be more prevalent among individuals with RAF1‐ , RIT1‐ , HRAS‐, and NSML‐associated PTPN11 mutations, with prevalence as high as 80% in some genotypes . While HCM is relatively rare in children under 1 year of age, HCM related to NS most often presents in the first year of life, being the leading genetic cause of HCM in this age group, and a leading cause of morbidity and mortality among infants and children with NS .…”

Section: Introductionmentioning

confidence: 99%

“…[3][4][5] HCM is known to be more prevalent among individuals with RAF1-, RIT1-, HRAS-, and NSML-associated PTPN11 mutations, with prevalence as high as 80% in some genotypes. 6 While HCM is relatively rare in children under 1 year of age, HCM related to NS most often presents in the first year of life, being the leading genetic cause of HCM in this age group, and a leading cause of morbidity and mortality among infants and children with NS. [7][8][9] Children with NS and HCM also have a less favorable outcome when compared with age-matched children with idiopathic or familial/sarcomeric forms of HCM, with higher mortality (15% at 3 years compared with 11% in isolated HCM), and greater likelihood of heart failure symptoms at presentation.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Cardiac transplantation in children with Noonan syndrome

McCallen

Ameduri

Denfield

et al. 2019

Pediatric Transplantation

Self Cite

View full text Add to dashboard Cite

NS and related RAS/MAPK pathway (RASopathy) disorders are the leading genetic cause of HCM presenting in infancy. HCM is a major cause of morbidity and mortality in children with Noonan spectrum disorders, especially in the first year of life. Previously, there have been only isolated reports of heart transplantation as a treatment for heart failure in NS. We report on 18 patients with NS disorders who underwent heart transplantation at seven US pediatric heart transplant centers. All patients carried a NS diagnosis: 15 were diagnosed with NS and three with NSML. Sixteen of eighteen patients had comprehensive molecular genetic testing for RAS pathway mutations, with 15 having confirmed pathogenic mutations in PTPN11, RAF1, and RIT1 genes. Medical aspects of transplantation are reported as well as NS‐specific medical issues. Twelve of eighteen patients described in this series were surviving at the time of data collection. Three patients died following transplantation prior to discharge from the hospital, and another three died post‐discharge. Heart transplantation in NS may be a more frequent occurrence than is evident from the literature or registry data. A mortality rate of 33% is consistent with previous reports of patients with HCM transplanted in infancy and early childhood. Specific considerations may be important in evaluation of this population for heart transplant, including a potentially increased risk for malignancies as well as lymphatic, bleeding, and coagulopathy complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Other Comorbiditiesmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Cardiac transplantation in children with Noonan syndrome

McCallen

Ameduri

Denfield

et al. 2019

Pediatric Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

Mary Ella Mascia Pierpont: Geneticist, scientist, mentor, friend (1945–2020)

Pierpont

Berry

Lin

et al. 2020

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Mary Ella spent the next 4 years of her medical training in several different positions, as residency and fellowship training were at that time far less regimented than now. Her first 2 years were spent at Georgetown University Hospital in Washington, DC, where she completed an Internship and year of Pediatrics focused on Development and Clinical Genetics. She then made what proved to be her most important move to the University of Minnesota, spending first a year in Laboratory Medicine and Pathology, and then a final year in Pediatrics. By this

show abstract