title: Frequency and natural history of inherited bone marrow failure syndromes: the Israeli Inherited Bone Marrow Failure Registry.
abstract: BACKGROUND
  Inherited bone marrow failure syndromes are rare genetic disorders characterized by bone marrow failure, congenital anomalies, and cancer predisposition. Available single disease registries provide reliable information regarding natural history, efficacy and side effects of treatments, and contribute to the discovery of the causative genes. However, these registries could not shed light on the true incidence of the various syndromes. We, therefore, established an Israeli national registry in order to investigate the relative frequency of each of these syndromes and their complications.
  
  
  METHODS
  Patients were registered by their hematologists in all 16 medical centers in Israel. We included patients with Fanconi anemia, severe congenital neutropenia, Diamond-Blackfan anemia, congenital amegakaryocytic thrombocytopenia, dyskeratosis congenita, Shwachman-Diamond syndrome, and thrombocytopenia with absent radii.
  
  
  RESULTS
  One hundred and twenty-seven patients diagnosed between 1966 and 2007 were registered. Fifty-two percent were found to have Fanconi anemia, 17% severe congenital neutropenia, 14% Diamond-Blackfan anemia, 6% congenital amegakaryocytic thrombocytopenia, 5% dyskeratosis congenita, 2% Shwachman-Diamond syndrome, and 2% thrombocytopenia with absent radii. No specific diagnosis was made in only 2 patients. Of the thirty patients (24%) developing severe bone marrow failure, 80% had Fanconi anemia. Seven of 9 patients with leukemia had Fanconi anemia, as did all 6 with solid tumors. Thirty-four patients died from their disease; 25 (74%) had Fanconi anemia and 6 (17%) had severe congenital neutropenia.
  
  
  CONCLUSIONS
  This is the first comprehensive population-based study evaluating the incidence and complications of the different inherited bone marrow failure syndromes. By far the most common disease was Fanconi anemia, followed by severe congenital neutropenia and Diamond-Blackfan anemia. Fanconi anemia carried the worst prognosis, with severe bone marrow failure and cancer susceptibility. Diamond-Blackfan anemia had the best prognosis. The data presented provide a rational basis for prevention programs and longitudinal surveillance of the complications of inherited bone marrow failure syndromes.
authors.affiliation: Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, 14 Kaplan Street, Petah Tiqva 49, Israel. htamary@post.tau.ac.il
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
authors.forename: Daniella
authors.initials: D
authors.lastname: Nishri
authors.forename: Joanne
authors.initials: J
authors.lastname: Yacobovich
authors.forename: Rama
authors.initials: R
authors.lastname: Zilber
authors.forename: Orly
authors.initials: O
authors.lastname: Dgany
authors.forename: Tanya
authors.initials: T
authors.lastname: Krasnov
authors.forename: Shraga
authors.initials: S
authors.lastname: Aviner
authors.forename: Polina
authors.initials: P
authors.lastname: Stepensky
authors.forename: Shoshana
authors.initials: S
authors.lastname: Ravel-Vilk
authors.forename: Menachem
authors.initials: M
authors.lastname: Bitan
authors.forename: Chaim
authors.initials: C
authors.lastname: Kaplinsky
authors.forename: Ayelet
authors.initials: A
authors.lastname: Ben Barak
authors.forename: Ronit
authors.initials: R
authors.lastname: Elhasid
authors.forename: Joseph
authors.initials: J
authors.lastname: Kapelusnik
authors.forename: Ariel
authors.initials: A
authors.lastname: Koren
authors.forename: Carina
authors.initials: C
authors.lastname: Levin
authors.forename: Dina
authors.initials: D
authors.lastname: Attias
authors.forename: Ruth
authors.initials: R
authors.lastname: Laor
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
mesh_terms: D000293:Adolescent; D000328:Adult; D001855:Bone Marrow Diseases / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D019337:Hematologic Neoplasms / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007557:Israel / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D012042:Registries / Q000706:statistics & numerical data*; D011795:Surveys and Questionnaires; D013577:Syndrome; D055815:Young Adult