Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Digestive System Diseases

Skin and Connective Tissue Diseases

Neoplasms

Rare Diseases

Syndrome

Anemia

Anemia, Aplastic

Bone Marrow Failure Disorders

Pancytopenia

Disease Susceptibility

Fanconi Syndrome

Fanconi Anemia

Congenital Bone Marrow Failure Syndromes

Shwachman-Diamond Syndrome

Anemia, Diamond-Blackfan

Dyskeratosis Congenita

Hemoglobinuria

Hemoglobinuria, Paroxysmal

Hematologic Diseases

Bone Marrow Diseases

Anemia, Hypoplastic, Congenital

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

Metabolic Diseases

Renal Tubular Transport, Inborn Errors

Kidney Diseases

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Cytopenia

Hemolysis

Anemia, Hemolytic

Preleukemia

Myelodysplastic Syndromes

Red-Cell Aplasia, Pure

Congenital Abnormalities

Skin Abnormalities

Genetic Diseases, X-Linked

Skin Diseases

Skin Diseases, Genetic

Exocrine Pancreatic Insufficiency

Pancreatic Diseases

Gastrointestinal Diseases

Metabolism, Inborn Errors

Lipid Metabolism, Inborn Errors

Lipid Metabolism Disorders

Lipomatosis

Lipomatosis, Multiple Symmetrical

Infant, Newborn, Diseases

Aplastic Anemia

Congenital Aplastic Anemia

Diamond-Blackfan Anemia

Pure Red Cell Aplasia

Multiple Symmetric Lipomatosis

All families with a member who has one of the relevant syndromes.

NCI Family Study Referrals

Neelam Giri, M.D.

Background:

A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.

Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers.

Patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer.

These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer.

Carriers of IBMFS pathogenic variant(s) are at increased risk of cancer.

The prototype disorder is Fanconi's Anemia (FA); other IBMFS will also be studied.

Objectives:

To determine the types and incidence of specific cancers in patients with an IBMFS.

To investigate the relevance of IBMFS pathogenic variant(s) in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers.

To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s).

To determine the risk of cancer in IBMFS carriers.

Eligibility:

North American families with a proband with an IBMFS.

IBMFS suspected by phenotype, confirmed by pathogenic variant(s) in an IBMFS gene, or by clinical diagnostic test.

Fanconi's anemia: birth defects, marrow failure, early onset malignancy; positive chromosome breakage result.

Diamond-Blackfan anemia: pure red cell aplasia; elevated red cell adenosine deaminase.

Dyskeratosis congenita: dysplastic nails, lacey pigmentation, leukoplakia; marrow failure.

Shwachman-Diamond Syndrome: malabsorption; neutropenia.

Amegakaryocytic thrombocytopenia: early onset thrombocytopenia.

Thrombocytopenia absent radii: absent radii; early onset thrombocytopenia.

Severe Congenital Neutropenia: neutropenia, pyogenic infections, bone marrow maturation arrest.

Pearson's Syndrome: malabsorption, neutropenia, marrow failure, metabolic acidosis; ringed sideroblasts.

Other bone marrow failure syndromes: e.g. Revesz Syndrome, WT, IVIC, radio-ulnar synostosis, ataxia-pancytopenia.

First degree relatives of IBMFS-affected subjects as defined here, i.e. siblings (half or full), biologic parents, and children.

Grandparents of IBMFS-affected subjects.

Patients in the general population with sporadic tumors of the types seen in the IBMFS (head and neck, gastrointestinal, and anogenital cancer), with none of the usual risk factors (e.g. smoking, drinking, HPV).

Design:

Natural history study, with questionnaires, clinical evaluations, clinical and research laboratory test, review of medical records, cancer surveillance.

Primary endpoints are all cancers, solid tumors, and cancers specific to each type of IBMFS.

Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones....

Study Description:

This is a natural history study involving questionnaires, clinical and research evaluations, clinical and research laboratory tests, review of medical records, cancer surveillance. A prospective cohort of Inherited Bone Marrow Failure Syndrome (IBMFS) will provide new information regarding cancer rates and types in these disorders.

Pathogenic variant(s) in IBMFS genes are relevant to carcinogenesis in sporadic cancers.

This study will determine whether patients with IBMFS who develop cancer differ in their genetic and/or environmental features from patients with IBMFS who do not develop cancer.

These cancer-prone families are well suited for cancer screening and prevention trials targeting those at increased genetic risk of cancer.

Carriers of IBMFS gene pathogenic variant(s) are at increased risk of cancer.

The prototype disorder is Fanconi Anemia (FA); other IBMFS will also be studied.

Objectives:

To determine the types and incidence of specific cancers in patients with an IBMFS.

To investigate the relevance of IBMFS gene pathogenic variants in the carcinogenesis pathway of the sporadic counterparts of IBMFS-associated cancers.

To identify risk factors for IBMFS-related cancers in addition to the primary germline pathogenic variant(s).

To determine the risk of cancer in IBMFS carriers.

Endpoints:

Primary Endpoint:

-All cancers, solid tumors, and cancers specific to each type of IBMFS.

Secondary Endpints:

-Secondary endpoints are markers of pre-malignant conditions, such as leukoplakia, serum or tissue evidence of carcinogenic viruses, and bone marrow morphologic myelodyplastic syndrome or cytogenetic clones.

Cancer in Inherited Bone Marrow Failure Syndromes

Etiologic Investigation of Cancer Susceptibility in Inherited Bone Marrow Failure Syndromes: A Natural History Study

Establish a cohort of families with IBMFS

Compare biology of IBMFS patients with general populations

Identify differences between patients with IBMFS who develop cancer and those who don't

Determine risk of cancer in IBMFS patients with specific gene mutations

National Cancer Institute (NCI)

Spots Global Cancer Trial Database for dyskeratosis congenita