Hematological Anomalies in Children With Rasopathy

Study Overview
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Brief Summary
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During childhood, patients with RASopathies (Noonan syndrome and related diseases) can harbor various hematological anomalies ranging from isolated monocytosis, myelemia, thrombocytopenia or splenomegaly to myeloproliferative disorders. These anomalies may spontaneously disappear or persist, sometimes leading to juvenile myelomonocytic leukemia. Guidelines for initial screening and subsequent hematological follow-up have recently been published in France: peripheral blood analysis should be performed in all newly diagnosed patients and followed by biannual peripheral blood analysis in infants until the age of 2 years. In order to describe the characteristics of these abnormalities in terms of their incidence, age of occurrence, evolution and relation to genotype, we are conducting a longitudinal prospective study whose aim is to analyze peripheral blood cell counts and smears at diagnosis and one year later. In patients <3 years of age recruited at certain centers, biobanking of mononuclear cells will be performed. These data could yield a new insight into hematological anomalies in patients with RASopathies and thereby help physicians to determine the appropriate rhythm for hematological follow-up according to genotype.

Official Title
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Hematological Anomalies in Children With Rasopathy

Conditions
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RAS Mutation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 16 years Patient with genetically confirmed Noonan syndrome, type 1 neurofibromatosis, Noonan syndrome with multiple lentigines, CBL syndrome, Costello syndrome, cardiofaciocutaneous syndrome or Legius syndrome i.e. with a germline mutation of one of these genes: PTPN11, SOS1, NRAS, RAF1, BRAF, SHOC2, MEK1, MEK2, CBL, NF1, SPRED1, KRAS, HRAS, NF1, SHOC2, LZTR1, SOS2, RIT1, RASA2, RRAS, PPP1CB, or a new gene of interest published during the recruitment period No history of hematological malignancy Written informed consent obtained from the parents Health insurance Exclusion Criteria: History of malignant hematological pathology

Ages Eligible for Study
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Maximum Age: 15 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with hematological abnormalities |  | at inclusion (within 6 months after diagnosis) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with hematological abnormalities according to genetic abnormality |  | at inclusion (within 6 months after diagnosis) | 
| Proportion of patients with hematological abnormalities according to age |  | at inclusion (within 6 months after diagnosis) | 
| Proportion of patients with hematological abnormalities |  | at 1 year after inclusion | 
| Proportion of patients with hematological abnormalities according to age |  | at 1 year after inclusion | 
| Proportion of patients with hematological abnormalities according to genetic abnormalities |  | at 1 year after inclusion | 
| Evolution of proportion of patients with hematological abnormalities during childhood |  | at 5 years post-inclusion | 
| Event-free survival |  | at one year post-inclusion | 
| Event-free survival |  | at 5 years post-inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RASopathie