Noonan syndrome and RASopathies: Clinical features, diagnosis and management

Lee, Beom Hee; Yoo, Han‐Wook

doi:10.5734/jgm.2019.16.1.1

Cited by 9 publications

(7 citation statements)

References 47 publications

(113 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…60 61 RASopathies include NS, Noonan-like syndrome, Costello syndrome, cardiofaciocutaneous syndrome, and NS with multiple lentigines (LEOPARD syndrome). 62 In our case study, our patient has NS and PFH. Lan et al also described a case of NS with cerebral hemorrhage.…”

Section: Discussionmentioning

confidence: 67%

Comprehensive Clinical and Neuroimaging Review of Posterior Fossa Hemorrhage in Preterm and Term Newborns

Hsu,

Zhu,

Islam

et al. 2023

Journal of Pediatric Neurology

View full text Add to dashboard Cite

Posterior fossa hemorrhage (PFH) is a highly morbid condition in preterm and term infants. In this article, we aim to first describe a case of PFH, and using this example, provide a comprehensive narrative review of the pathophysiology, risk factors, diagnosis, and management of PFH. Management may differ depending on the etiology and based on careful consideration of the risks and benefits of surgical versus conservative management.

show abstract

Section: Discussionmentioning

confidence: 67%

Comprehensive Clinical and Neuroimaging Review of Posterior Fossa Hemorrhage in Preterm and Term Newborns

Hsu,

Zhu,

Islam

et al. 2023

Journal of Pediatric Neurology

View full text Add to dashboard Cite

show abstract

“…The clinical and genetic heterogeneity of the RASopathies syndromes per se indicates the need for a more comprehensive technique for molecular diagnosis; however, except for specific clinical phenotypes orientating a molecular target as a first-tier in the diagnostic flowchart. 2 , 6 , 34 , 35 In such cases, Sanger sequencing can be used, especially when genes carry hotspots for the suspected phenotypes. By this mean, we screened six unrelated cases with NS phenotype for exons 3 and 8 in the PTPN11 gene.…”

Section: Discussionmentioning

confidence: 99%

RASopathy Cohort of Patients Enrolled in a Brazilian Reference Center for Rare Diseases: A Novel Familial LZTR1 Variant and Recurrent Mutations

Rabelo¹,

Gomes²,

Moraes³

et al. 2022

TACG

View full text Add to dashboard Cite

Purpose Noonan syndrome and related disorders are genetic conditions affecting 1:1000–2000 individuals. Variants causing hyperactivation of the RAS/MAPK pathway lead to phenotypic overlap between syndromes, in addition to an increased risk of pediatric tumors. DNA sequencing methods have been optimized to provide a molecular diagnosis for clinical and genetic heterogeneity conditions. This work aimed to investigate the genetic basis in RASopathy patients through Next Generation Sequencing in a Reference Center for Rare Diseases (IFF/Fiocruz) and implement the precision medicine at a public health institute in Brazil. Patients and Methods This study comprises 26 cases with clinical suspicion of RASopathies. Sanger sequencing was used to screen variants in exons usually affected in the PTPN11 and HRAS genes for cases with clinical features of Noonan and Costello syndrome, respectively. Posteriorly, negative and new cases with clinical suspicion of RASopathy were analyzed by clinical or whole-exome sequencing. Results Molecular analysis revealed recurrent variants and a novel LZTR1 missense variant: 24 unrelated individuals with pathogenic variants [ PTPN11 (11), NF1 (2), SOS1 (2), SHOC2 (2), HRAS (1), BRAF (1), LZTR (1), RAF1 (1), KRAS (1), RIT1 (1), a patient with co-occurrence of PTPN11 and NF1 mutations (1)]; familial cases carrying a known pathogenic variant in PTPN11 (mother-two children), and a previously undescribed paternally inherited variant in LZTR1 . The comparative modeling analysis of the novel LZTR1 variant p.Pro225Leu showed local and global changes in the secondary and tertiary structures, showing a decrease of about 1% in the β-sheet content. Furthermore, evolutionary conservation indicated that Pro225 is in a highly conserved region, as observed for known dominant pathogenic variants in this protein. Conclusion Bringing precision medicine through NGS towards congenital syndromes promotes a better understanding of complex clinical and/or undiagnosed cases. The National Policy for Rare Diseases in Brazil emphasizes the importance of incorporating and optimizing diagnostic methodologies in the Unified Brazilian Health System (SUS). Therefore, this work is an important step for the NGS inclusion in diagnostic genetic routine in the public health system.

show abstract

“…HC may belong to various dysmorphic syndromes including RASopathies, disorders caused by germline mutations of the RAS/MAPK signaling pathway, or its regulators [3,105,107,125]. Glomus tumors of the fingers (benign neoplasms that arise from the glomus body, a specialized thermoregulatory shunt which is concentrated in the fingers and toes) are associated with neurofibromatosis and their appearance is determined by the loss of neurofibromin function [126,127].…”

Section: Overgrowth Syndromesmentioning

confidence: 99%

Macrocephaly and Finger Changes: A Narrative Review

Lazea,

Vulturar,

Chiș

et al. 2024

IJMS

View full text Add to dashboard Cite

Macrocephaly, characterized by an abnormally large head circumference, often co-occurs with distinctive finger changes, presenting a diagnostic challenge for clinicians. This review aims to provide a current synthetic overview of the main acquired and genetic etiologies associated with macrocephaly and finger changes. The genetic cause encompasses several categories of diseases, including bone marrow expansion disorders, skeletal dysplasias, ciliopathies, inherited metabolic diseases, RASopathies, and overgrowth syndromes. Furthermore, autoimmune and autoinflammatory diseases are also explored for their potential involvement in macrocephaly and finger changes. The intricate genetic mechanisms involved in the formation of cranial bones and extremities are multifaceted. An excess in growth may stem from disruptions in the intricate interplays among the genetic, epigenetic, and hormonal factors that regulate human growth. Understanding the underlying cellular and molecular mechanisms is important for elucidating the developmental pathways and biological processes that contribute to the observed clinical phenotypes. The review provides a practical approach to delineate causes of macrocephaly and finger changes, facilitate differential diagnosis and guide for the appropriate etiological framework. Early recognition contributes to timely intervention and improved outcomes for affected individuals.

show abstract

Noonan syndrome and RASopathies: Clinical features, diagnosis and management

Cited by 9 publications

References 47 publications

Comprehensive Clinical and Neuroimaging Review of Posterior Fossa Hemorrhage in Preterm and Term Newborns

Comprehensive Clinical and Neuroimaging Review of Posterior Fossa Hemorrhage in Preterm and Term Newborns

RASopathy Cohort of Patients Enrolled in a Brazilian Reference Center for Rare Diseases: A Novel Familial LZTR1 Variant and Recurrent Mutations

Macrocephaly and Finger Changes: A Narrative Review

Contact Info

Product

Resources

About