Frequency and natural history of inherited bone marrow failure syndromes: the Israeli Inherited Bone Marrow Failure Registry.
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.
Tamary
Hannah
H
Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, 14 Kaplan Street, Petah Tiqva 49, Israel. htamary@post.tau.ac.il
Nishri
Daniella
D
Yacobovich
Joanne
J
Zilber
Rama
R
Dgany
Orly
O
Krasnov
Tanya
T
Aviner
Shraga
S
Stepensky
Polina
P
Ravel-Vilk
Shoshana
S
Bitan
Menachem
M
Kaplinsky
Chaim
C
Ben Barak
Ayelet
A
Elhasid
Ronit
R
Kapelusnik
Joseph
J
Koren
Ariel
A
Levin
Carina
C
Attias
Dina
D
Laor
Ruth
R
Yaniv
Isaac
I
Rosenberg
Philip S
PS
Alter
Blanche P
BP
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