Table 3.

Differential Diagnosis of Diamond-Blackfan Anemia: Genetic Conditions with Bone Marrow Failure

GeneDisorderMOIClinical Characteristics
ACD
CTC1
DKC1
NHP2
NOP10
PARN
RTEL1
TERC
TERT
TINF2
WRAP53 		Dyskeratosis congenita (DC)XL
AD
AR		Telomere biology disorder characterized by a classic triad of dysplastic nails, lacy reticular pigmentation of the upper chest &/or neck, & oral leukoplakia (triad may not be present in all persons). ↑ risk for progressive BMF, MDS or acute AML, solid tumors, & pulmonary fibrosis.
ADA2
(CECR1)		 Adenosine deaminase 2 (ADA2) deficiency ARVasculitis &/or a DBA phenotype in persons w/ADA2 deficiency
BRCA2
BRIP1
FANCA
FANCB
FANCC
FANCD2
FANCE
FANCF
FANCG
FANCI
(21 genes 1)		Fanconi anemia (FA)AR
AD
XL		Physical abnormalities (~75% of affected persons): short stature, abnormal skin pigmentation, skeletal malformations, microcephaly, ophthalmic & genitourinary tract anomalies. Progressive BMF w/pancytopenia. ↑ risk hematologic malignancies (AML) & solid tumors (head & neck, skin, GI tract, & genital tract).
DNAJC21
EFL1
SBDS
SRP54 		Shwachman-Diamond syndrome (SDS)AR
AD		Exocrine pancreatic dysfunction w/malabsorption, malnutrition, growth failure, bone abnormalities, persistent or intermittent neutropenia, & recurrent infections; cytopenias & susceptibility to MDS & AML.
EPO DBA-like (OMIM 617911)ARRare pathogenic variants can present w/PRCA but will respond to treatment w/recombinant EPO, unlike DBA.
Mitochondrial
DNA 2		Pearson syndrome (See Mitochondrial DNA Deletion Syndromes.)MatSideroblastic anemia of childhood, pancytopenia, exocrine pancreatic failure, & renal tubular defects. Progressive liver failure & intractable metabolic acidosis typically result in death in infancy. Those who survive develop neurologic symptoms.
MYSM1 Bone marrow failure syndrome 4 (OMIM 618116)ARTransfusion-dependent anemia in early childhood w/other cytopenias
NHEJ1 SCID w/microcephaly, growth retardation, & sensitivity to ionizing radiation (OMIM 611291)ARImmunodeficiency & dysmorphic facies; 50% have anemia & thrombocytopenia.
RMRP Cartilage-hair hypoplasia – anauxetic dysplasia (CHH-AD)ARSevere short-limb short stature usually present in newborns; joint hypermobility, fine silky hair, immunodeficiency, anemia, ↑ risk for malignancy, gastrointestinal dysfunction, & impaired spermatogenesis. Clinical manifestations are variable even w/in a family.

AD = autosomal dominant; AML = acute myeloid leukemia; AR = autosomal recessive; BMF = bone marrow failure; DBA = Diamond-Blackfan anemia; DD = developmental delay; EPO = erythropoietin; Mat = maternal; MDS = myelodysplastic syndrome; MOI = mode of inheritance; PRCA = acquired pure red cell aplasia; SCID = severe combined immunodeficiency; XL = X-linked

1.

Listed genes represent the most commonly associated genes. See Fanconi Anemia for other genes associated with this phenotype.

2.

Pearson syndrome is most often caused by de novo deletions in mitochondrial DNA; rearrangements (large-scale partial deletions and duplications) have also been found [Morel et al 2009].

From: Diamond-Blackfan Anemia

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