FaCD Online Syndrome Fact Sheet

Last updated: 02 Jun 2009

Name: Diamond-Blackfan Anemia

Synonym: DBA, Congenital Hypoplastic Anemia, Blackfan-Diamond Anemia, incl.: Aase syndrome

Mode of Inheritance: AR?/ AD? / spor

Genes

RPS19, mapped to 19q13

Tumor features

hepatic tumor
hepatocellular cancer (hepatoma)
Hodgkin disease (Hodgkin's lymphoma)
leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
myelodysplastic syndrome (MDS)
non-Hodgkin lymphoma

Tumor features (possible)

bone, malignant fibrous histiocytoma of the
osteosarcoma

Non-tumor features

anemia
bifid thumb
cataract, congenital
cleft palate
growth deficieny
hypertelorism
ionizing radiation sensitivity, increased
microcephaly
micrognathia
neck, webbed
palate, high arched
retrognathism
strabismus
thumbs, hypoplastic or absent
triphalangeal thumb
vertebral anomalies

Comment

This anemia manifests in neonates and infants, due to a red-cell aplasia in that period. There is a selective decrease in erythroid pre-cursor cells. In approximately 30-40% of the patients, one or more congenital defects are present: particularly craniofacial dysmorphisms, growth failure, neck anomalies and thumb malformations.[1-5,6,11,15]. Those cases associated with triphalangeal thumbs have been referred to as Aase syndrome, however, it is doubtful whether this represents a disorder distinct from DBA[6]. Hematolymphoproliferative disorders have been reported in approximately 2.5% of the patients with DBA, AML being the most frequent complication[4;5;7;12;13]. Malignant fibrous histiocytoma of the femur in a 23-year-old man with Blackfan-Diamond syndrome was reported by Turcotte et al.[8]. Other tumors include osteosarcoma and hepatocellular cancer [5].

Approximately 75 % of DBA cases are sporadic, familial cases fitting autosomal recessive (AR) or autosomal dominant (AD) modes of inheritance have been reported[4]. X-ray-sensitivity of lymphocytes of DBA patients is increased[9]. Despite its clinical heterogeneity, there appears to be genetic homogeneity: DBA has been mapped to 19q13 in families presenting with AR and AD inheritance. Germline mutations in the RPS19 gene, mapped to this region, have been detected in 25 % of DBA patients[10]

Links

Diamond Blackfan Anæmia Support Group, UK 18 1 08

References

[1] Viskochil DH, Carey JC, Glader BE, Rothstein G, Christensen RD. Congenital hypoplastic (Diamond-Blackfan) anemia in seven members of one kindred. Am J Med Genet 1990; 35:251-256.
[2] Gojic V, van 't Veer-Korthof ET, Bosch LJ, Puyn WH, van Haeringen A. Congenital hypoplastic anemia: another example of autosomal dominant transmission. Am J Med Genet 1994; 50:87-89.
[3] McLennan AC, Chitty LS, Rissik J, Maxwell DJ. Prenatal diagnosis of Blackfan-Diamond syndrome: case report and review of the literature. Prenat Diagn 1996; 16:349-353.
[4] Krijanovski OI, Sieff CA. Diamond-Blackfan anemia. Hematol Oncol Clin North Am 1997; 11(6):1061-1077.
[5] Willig TN, Gazda H, Sieff CA. Diamond-Blackfan anemia. Curr Opin Hematol 2000; 7(2):85-94.
[6] Halperin DS, Freedman MH. Diamond-Blackfan anemia: etiology, panthophysiology, and treatment. Am J Ped Hematol Oncol 1989; 11(4):380-394.
[7] Van Dijken PJ, Verwijs W. Diamond-Blackfan anemia and malignancy. A case report and a review of the literature [see comments]. Cancer 1995; 76(3):517-520.
[8] Turcotte R, Bard C, Marton D, Schurch W, Lafontaine E. Malignant fibrous histiocytoma in a patient with Blackfan- Diamond anemia. Can Assoc Radiol J 1994; 45(5):402-410.
[9] Van Diemen PCM, Maasdam D, Darroudi F, Natarajan AT. X-ray-sensitivity of lymphocytes of aplastic- and Diamond- Blackfan- anemia patients as detected by conventional cytogenetic and chromosome painting techniques. Mutat.Res.Fundam.Mol.Mech.Mut. 373[2], 225-235. 1997.
[10] Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N. The gene encoding ribosomal protein S19 is mutated in Diamond- Blackfan anaemia. Nat Genet 21[2], 169-175. 1999.
[11] Gazda HT, Sieff CA. Recent insights into the pathogenesis of Diamond-Blackfan anaemia. British journal of haematology 2006; 135(2):149-57.
[12] Yaris N, Erduran E, Cobanoglu U. Hodgkin lymphoma in a child with Diamond Blackfan anemia. Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology 2006; 28(4):234-6.
[13] Hayashi AK, Kang YS, Smith BM. Non-Hodgkin's lymphoma in a patient with Diamond-Blackfan anemia. AJR. American journal of roentgenology 1999; 173(1):117-8.
[14] Lipton JM, Federman N, Khabbaze Y, Schwartz CL, Hilliard LM, Clark JI, Vlachos A, . Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry. Journal of pediatric hematology/oncology : official journal of the American Society of Pediatric Hematology/Oncology 2001; 23(1):39-44.
[15] Lipton JM, Ellis SR. Diamond-Blackfan anemia: diagnosis, treatment, and molecular pathogenesis. Hematol Oncol Clin North Am. 2009 Apr;23(2):261-82.