Longitudinal Studies of Patient With FPDMM

Study Overview
=================
Brief Summary
-----------------
Background: Genes tell the body and its cells how to work. Familial platelet disease (FPD) or FPD with associated malignancies (FPDMM) is caused by a variant in the gene RUNX1. People with this disease may have problems with their blood and bleed for a long time when they are injured. Researchers want to learn more about RUNX1 variants and FPD. Objective: To learn more about FPD in people with RUNX1 variants to lead to better diagnosis, monitoring, and treatment. Eligibility: People any age with a suspected or confirmed RUNX1 variant People who have a family member with the variant Design: All participants will be screened with a phone call and a blood, saliva, or cheek cell sample. Participants with a suspected or confirmed variant will have 1 visit. It will last about 2 days. They will then have visits at least once a year. Visits will include: Medical history and physical exam Blood tests or saliva sample Possible skin biopsy: A small piece of the participant s skin will be removed. Bone marrow aspiration or biopsy: The participant s bone marrow will be removed by needle from a large bone such as the hip bone. Possible apheresis: Blood will be removed from the body and certain blood cells will be taken out. The rest of the blood is returned to the body. Between visits, participants with a suspected or confirmed variant will keep a diary of disease symptoms and signs. Samples from all participants may be used for genetic testing

Detailed Description
-----------------
Germline mutations in RUNX1 are responsible for familial platelet disorder with associated myeloid malignancies (FPDMM, or simply FPD), an autosomal dominant disease characterized by defective megakaryocytic development, low platelet counts, prolonged bleeding times, and a life-long risk of developing hematological malignancies. Disease penetrance and clinical presentations vary among families with different germline RUNX1 variants, and even among affected individuals within a single family. Currently there are no biomarkers or assays to predict which patients will progress to malignancy, and some patients present with acute myeloid leukemia (AML) as their initial manifestation of the germline syndrome. We propose to characterize the etiology and natural history of patients with FPDMM and RUNX1 variants, both known and yet-to-be discovered. We will investigate those patients and families with FPDMM-like diseases but without RUNX1 variants, to understand the genetic basis for their diseases. In so doing, we will expand our knowledge about this disorder and provide access to patients of interest for research, teaching, and clinical experience. The knowledge gained through this study will lead to better understanding of the disease progression, both clinically and at molecular levels, which may result in the development of better diagnosis, monitoring, and innovative therapies.

Official Title
-----------------
Longitudinal Studies of Patients and Families With Familial Platelet Disorders With Associated Myeloid Malignancy (FPDMM) Caused by RUNX1 Germline Variants or FPDMM-Like Conditions

Conditions
-----------------
Inherited Hematological Diseases, Rare Diseases, FPDMM

Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITIERIA: Patients enrolled in this protocol will have been referred with a known or suspected variant in the RUNX1 gene. Patients with suspected RUNX1 variants are those with clinical features of FPD but who have not been tested for RUNX1, or who were negative on standard testing. The Principal Investigator, along with consulting specialists, will review the medical records of prospective patients and offer enrollment based upon the potential to help the individual, to learn from the patient, or to initiate clinical or basic research suggested by the patient s workup. Unaffected family members may be asked to enroll in the study to provide specimens (saliva, blood, skin) for genetic testing, next-generation sequencing, and other related studies. Enrolled subjects can be any sex and any age. There are no upper or lower age restrictions on this study. EXCLUSION CRITIERIA: There are no exclusionary criteria.

Ages Eligible for Study
-----------------
Minimum Age: 1 Day

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Family<br>Direct family members of enrolled patients will be asked to enroll in the study to provide specimens for genetic testing, next-generation sequencing, and other related studies. | |
| RUNX1<br>Patients enrolled in this protocol will have been referred with a known or suspected RUNX1 mutation. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Natural History | This protocol continues the decades-long tradition of identifying and examining patients with rare genetic diseases and characterizing the natural history. | Ongoing | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
inherited hematological diseases, Rare Diseases, Hematological Malignancies, Cancer, Acute Myeloid Leukemia, Natural History