Recent developments in neurofibromatoses and RASopathies: Management, diagnosis and current and future therapeutic avenues

Rauen, Katherine A.; Huson, Susan M.; Burkitt-Wright, Emma; Evans, D. Gareth; Farschtschi, Said; Ferner, Rosalie E.; Gutmann, David H.; Hanemann, C. Oliver; Kerr, Bronwyn; Legius, Eric; Parada, Luis F.; Patton, Michael A.; Peltonen, Juha; Ratner, Nancy; Riccardi, Vincent M.; Vaart, Thijs van der; Vikkula, Miikka; Viskochil, David; Zenker, Martin; Upadhyaya, Meena

doi:10.1002/ajmg.a.36793

Cited by 47 publications

(61 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The genetic group is characterized by chromosomal abnormalities (n = 12), including Down (n = 7) and Williams syndromes, and four children presented abnormal microarrays; Mendelian inheritance (n = 7), including fragile X and Cornelia de Lange syndromes, tuberous sclerosis, and one family with autosomal dominant microcephaly; and multifactorial inheritance (n = 12), including several congenital defects and attention deficit hyperactivity disorder. More details about this genetic group can be found in another publication [19]. Children in the idiopathic group (12.6%) presented suspected ID with distinguishing characteristics, such as impairments on adaptive behavior, overweight (BMI ≥17.53 in females and 17.71 in males), or dysmorphic features.…”

Section: Resultsmentioning

confidence: 99%

Intellectual Disability in a Birth Cohort: Prevalence, Etiology, and Determinants at the Age of 4 Years

Karam

Barros²,

Matijasevich³

et al. 2016

Public Health Genomics

View full text Add to dashboard Cite

Background: Intellectual disability (ID), characterized by impairments in intellectual function and adaptive behavior, affects 1-3% of the population. Many studies investigated its etiology, but few are cohort studies in middle-income countries. Aims: To estimate prevalence, etiology, and factors related to ID among children prospectively followed since birth in a Southern Brazilian city (Pelotas). Methods: In 2004, maternity hospitals were visited daily and births were identified. Live-born infants (n = 4,231) whose family lived in the urban area have been followed for several years. At the age of 2 and 4 years, performances in development and intelligence tests were evaluated using the Battelle Developmental Inventory and Wechsler Intelligence Scale, respectively. Children considered as having developmental delay were invited to attend a genetic evaluation. Results: At 4 years of age, the prevalence of ID was 4.5%, and the etiology was classified into 5 groups: environmental (44.4%), genetic (20.5%), idiopathic (12.6%), neonatal sequelae (13.2%), other diseases (9.3%). Most children presented impairment in two or more areas of adaptive behavior. There was no difference in prenatal care attendance or maternal schooling among the groups. Conclusion: For about 40% of children, ID was attributed to nonbiological factors, suggesting that the rate may be reduced with appropriate interventions early in life.

show abstract

Section: Resultsmentioning

confidence: 99%

Intellectual Disability in a Birth Cohort: Prevalence, Etiology, and Determinants at the Age of 4 Years

Karam

Barros²,

Matijasevich³

et al. 2016

Public Health Genomics

View full text Add to dashboard Cite

show abstract

“…RASopathies are genetic syndromes caused by germline mutations in genes encoding components or regulators of the RAS/MAPK pathway 48,49 . Given the key role of the RAS/MAPK pathway in normal development, mutations in RAS/MAPK pathway genes in these patients result in developmental abnormalities in multiple organ systems as well as predisposition to cancers.…”

Section: The Nf1 Proteinmentioning

confidence: 99%

The NF1 gene in tumor syndromes and melanoma

Kiuru

Busam

2017

Laboratory Investigation

157

133

View full text Add to dashboard Cite

Activation of the RAS/MAPK pathway is critical in melanoma. Melanoma can be grouped into four molecular subtypes based on their main genetic driver: BRAF-mutant, NRAS-mutant, NF1-mutant, and triple wild-type tumors. The NF1 protein, neurofibromin 1, negatively regulates RAS proteins through GTPase activity. Germline mutations in NF1 cause neurofibromatosis type I, a common genetic tumor syndrome caused by dysregulation of the RAS/MAPK pathway, i.e. RASopathy. Melanomas with NF1 mutations typically occur on chronically sun-exposed skin or in older individuals, show a high mutation burden, and are wild-type for BRAF and NRAS. Additionally, NF1 mutations characterize certain clinicopathologic melanoma subtypes, specifically desmoplastic melanoma. This review discusses the current knowledge of the NF1 gene and neurofibromin 1 in neurofibromatosis type I and in melanoma.

show abstract

“…[1][2][3]. NS features include abnormal growth (proportionate short stature and relative or absolute macrocephaly), congenital heart defects (most commonly pulmonary stenosis or hypertrophic cardiomyopathy), dysmorphism (hypertelorism with downslanting palpebral fissures; ocular ptosis; low-set, posteriorly rotated ears; broad neck with low hairline; and thorax deformity), and abnormal skin and adnexa.…”

Section: The Rasopathiesmentioning

confidence: 99%

“…Additional features may include learning difficulties, ocular anomalies, feeding problems in infancy, cryptorchidism, disorders of pubertal timing, lymphatic anomalies, bleeding diathesis, and increased cancer risk. The group of RASopathies are described in detail below (1)(2)(3). Among these are neurofibromatosis type 1 (NF1); cancer surveillance in persons with NF1 is discussed in the CCR Pediatric Oncology Series article by Evans and colleagues (4).…”

Section: The Rasopathiesmentioning

confidence: 99%

Recommendations for Cancer Surveillance in Individuals with RASopathies and Other Rare Genetic Conditions with Increased Cancer Risk

Villani

Greer

Kalish

et al. 2017

Clinical Cancer Research

126

View full text Add to dashboard Cite

In October 2016, the American Association for Cancer Research held a meeting of international childhood cancer predisposition syndrome experts to evaluate the current knowledge of these syndromes and to propose consensus surveillance recommendations. Herein, we summarize clinical and genetic aspects of RASopathies and Sotos, Weaver, Rubinstein-Taybi, Schinzel-Giedion, and NKX2-1 syndromes as well as specific metabolic disorders known to be associated with increased childhood cancer risk. In addition, the expert panel reviewed whether sufficient data exist to make a recommendation that all patients with these disorders be offered cancer surveillance. For all syndromes, the panel recommends increased awareness and prompt assessment of clinical symptoms. Patients with Costello syndrome have the highest cancer risk, and cancer surveillance should be considered. Regular physical examinations and complete blood counts can be performed in infants with Noonan syndrome if specific PTPN11 or KRAS mutations are present, and in patients with CBL syndrome. Also, the high brain tumor risk in patients with L-2 hydroxyglutaric aciduria may warrant regular screening with brain MRIs. For most syndromes, surveillance may be needed for nonmalignant health problems. Clin Cancer Res; 23(12); e83–e90. ©2017 AACR. See all articles in the online-only CCR Pediatric Oncology Series.

show abstract

Recent developments in neurofibromatoses and RASopathies: Management, diagnosis and current and future therapeutic avenues

Cited by 47 publications

References 1 publication

Intellectual Disability in a Birth Cohort: Prevalence, Etiology, and Determinants at the Age of 4 Years

Intellectual Disability in a Birth Cohort: Prevalence, Etiology, and Determinants at the Age of 4 Years

The NF1 gene in tumor syndromes and melanoma

Recommendations for Cancer Surveillance in Individuals with RASopathies and Other Rare Genetic Conditions with Increased Cancer Risk

Contact Info

Product

Resources

About