U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Diamond-Blackfan anemia 21(DBA21)

MedGen UID:
1824003
Concept ID:
C5774230
Disease or Syndrome
Synonyms: DBA21; DIAMOND-BLACKFAN ANEMIA 21
 
Gene (location): HEATR3 (16q12.1)
 
Monarch Initiative: MONDO:0031071
OMIM®: 620072

Definition

Diamond-Blackfan anemia-21 (DBA21) is an autosomal recessive bone marrow failure syndrome that includes selective erythroid hypoplasia, anemia with transient thrombocytopenia, short stature, facial dysmorphism, limb abnormalities, cardiac defects, and intellectual disability (O'Donohue et al., 2022). For a general phenotypic description and discussion of genetic heterogeneity of Diamond-Blackfan anemia, see DBA1 (105650). [from OMIM]

Clinical features

From HPO
Osteosarcoma
MedGen UID:
10501
Concept ID:
C0029463
Neoplastic Process
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Hallux valgus
MedGen UID:
5416
Concept ID:
C0018536
Anatomical Abnormality
Lateral deviation of the great toe (i.e., in the direction of the little toe).
Cubitus valgus
MedGen UID:
490152
Concept ID:
C0158465
Acquired Abnormality
Abnormal positioning in which the elbows are turned out.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Preaxial hand polydactyly
MedGen UID:
237235
Concept ID:
C1395852
Congenital Abnormality
Supernumerary digits located at the radial side of the hand. Polydactyly (supernumerary digits) involving the thumb occurs in many distinct forms of high variability and severity. Ranging from fleshy nubbins over varying degrees of partial duplication/splitting to completely duplicated or even triplicated thumbs or preaxial (on the radial side of the hand) supernumerary digits.
Short toe
MedGen UID:
322858
Concept ID:
C1836195
Finding
A toe that appears disproportionately short compared to the foot.
Sandal gap
MedGen UID:
374376
Concept ID:
C1840069
Finding
A widely spaced gap between the first toe (the great toe) and the second toe.
Clinodactyly of the thumb
MedGen UID:
341643
Concept ID:
C1856888
Finding
Aortic regurgitation
MedGen UID:
8153
Concept ID:
C0003504
Disease or Syndrome
An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.
Atrial septal defect, ostium secundum type
MedGen UID:
91034
Concept ID:
C0344724
Congenital Abnormality
A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum.
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Erythroid hypoplasia
MedGen UID:
488912
Concept ID:
C0542035
Disease or Syndrome
Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Developmental dysplasia of the hip
MedGen UID:
1640560
Concept ID:
C4551649
Congenital Abnormality
Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000). Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006). CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970). Genetic Heterogeneity of Developmental Dysplasia of the Hip Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21. DDH3 (620690) is caused by mutation in the LRP1 gene (107770) on chromosome 12q13.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Widow peak
MedGen UID:
342891
Concept ID:
C1853486
Finding
Frontal hairline with bilateral arcs to a low point in the midline of the forehead.
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Horizontal eyebrow
MedGen UID:
478649
Concept ID:
C3277019
Finding
An eyebrow that extends straight across the brow, without curve.
Nevus
MedGen UID:
45074
Concept ID:
C0027960
Neoplastic Process
A nevus is a type of hamartoma that is a circumscribed stable malformation of the skin.
Cutis marmorata
MedGen UID:
78093
Concept ID:
C0263401
Disease or Syndrome
A reticular discoloration of the skin with cyanotic (reddish-blue appearing) areas surrounding pale central areas due to dilation of capillary blood vessels and stagnation of blood within the vessels. Cutis marmorata generally occurs on the legs, arms and trunk and is often more severe in cold weather.
Coarse hair
MedGen UID:
124454
Concept ID:
C0277959
Finding
Hair shafts are rough in texture.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Unilateral ptosis
MedGen UID:
401085
Concept ID:
C1866806
Finding
A unilateral form of ptosis.

Professional guidelines

PubMed

Gianferante MD, Wlodarski MW, Atsidaftos E, Da Costa L, Delaporta P, Farrar JE, Goldman FD, Hussain M, Kattamis A, Leblanc T, Lipton JM, Niemeyer CM, Pospisilova D, Quarello P, Ramenghi U, Sankaran VG, Vlachos A, Volejnikova J, Alter BP, Savage SA, Giri N
Haematologica 2021 May 1;106(5):1303-1310. doi: 10.3324/haematol.2020.246629. PMID: 32241839Free PMC Article
Bezzerri V, Api M, Allegri M, Fabrizzi B, Corey SJ, Cipolli M
Int J Mol Sci 2020 Jun 30;21(13) doi: 10.3390/ijms21134672. PMID: 32630050Free PMC Article
Vlachos A, Dahl N, Dianzani I, Lipton JM
Eur J Hum Genet 2013 Oct;21(10) Epub 2013 Mar 6 doi: 10.1038/ejhg.2013.34. PMID: 23463023Free PMC Article

Recent clinical studies

Etiology

Kapralova K, Jahoda O, Koralkova P, Gursky J, Lanikova L, Pospisilova D, Divoky V, Horvathova M
Int J Mol Sci 2020 Dec 17;21(24) doi: 10.3390/ijms21249652. PMID: 33348919Free PMC Article
Bezzerri V, Api M, Allegri M, Fabrizzi B, Corey SJ, Cipolli M
Int J Mol Sci 2020 Jun 30;21(13) doi: 10.3390/ijms21134672. PMID: 32630050Free PMC Article
Maisonneuve E, Ben M'Barek I, Leblanc T, Da Costa L, Friszer S, Pernot F, Thomas P, Castaigne V, Toly N'Dour C, Mailloux A, Cortey A, Jouannic JM
Fetal Diagn Ther 2020;47(2):156-164. Epub 2019 Sep 10 doi: 10.1159/000501554. PMID: 31505487
Alter BP
Blood 2017 Nov 23;130(21):2257-2264. doi: 10.1182/blood-2017-05-781799. PMID: 29167174Free PMC Article
Khincha PP, Savage SA
Semin Fetal Neonatal Med 2016 Feb;21(1):57-65. Epub 2015 Dec 24 doi: 10.1016/j.siny.2015.12.003. PMID: 26724991Free PMC Article

Diagnosis

Dorenkamp M, Porret N, Diepold M, Rovó A
Medicina (Kaunas) 2023 Nov 5;59(11) doi: 10.3390/medicina59111953. PMID: 38004002Free PMC Article
Maisonneuve E, Ben M'Barek I, Leblanc T, Da Costa L, Friszer S, Pernot F, Thomas P, Castaigne V, Toly N'Dour C, Mailloux A, Cortey A, Jouannic JM
Fetal Diagn Ther 2020;47(2):156-164. Epub 2019 Sep 10 doi: 10.1159/000501554. PMID: 31505487
Kedar PS, Harigae H, Ito E, Muramatsu H, Kojima S, Okuno Y, Fujiwara T, Dongerdiye R, Warang PP, Madkaikar MR
Int J Hematol 2019 Nov;110(5):618-626. Epub 2019 Aug 10 doi: 10.1007/s12185-019-02716-9. PMID: 31401766
Khincha PP, Savage SA
Semin Fetal Neonatal Med 2016 Feb;21(1):57-65. Epub 2015 Dec 24 doi: 10.1016/j.siny.2015.12.003. PMID: 26724991Free PMC Article
Tsilou ET, Giri N, Weinstein S, Mueller C, Savage SA, Alter BP
Ophthalmology 2010 Mar;117(3):615-22. Epub 2009 Dec 22 doi: 10.1016/j.ophtha.2009.08.023. PMID: 20022637Free PMC Article

Therapy

Vlachos A, Atsidaftos E, Lababidi ML, Muir E, Rogers ZR, Alhushki W, Bernstein J, Glader B, Gruner B, Hartung H, Knoll C, Loew T, Nalepa G, Narla A, Panigrahi AR, Sieff CA, Walkovich K, Farrar JE, Lipton JM
Pediatr Blood Cancer 2020 Dec;67(12):e28748. Epub 2020 Oct 6 doi: 10.1002/pbc.28748. PMID: 33025707Free PMC Article
Bezzerri V, Api M, Allegri M, Fabrizzi B, Corey SJ, Cipolli M
Int J Mol Sci 2020 Jun 30;21(13) doi: 10.3390/ijms21134672. PMID: 32630050Free PMC Article
Maisonneuve E, Ben M'Barek I, Leblanc T, Da Costa L, Friszer S, Pernot F, Thomas P, Castaigne V, Toly N'Dour C, Mailloux A, Cortey A, Jouannic JM
Fetal Diagn Ther 2020;47(2):156-164. Epub 2019 Sep 10 doi: 10.1159/000501554. PMID: 31505487
Bernini JC, Carrillo JM, Buchanan GR
J Pediatr 1995 Oct;127(4):654-9. doi: 10.1016/s0022-3476(95)70134-6. PMID: 7562296
Gillio AP, Faulkner LB, Alter BP, Reilly L, Klafter R, Heller G, Young DC, Lipton JM, Moore MA, O'Reilly RJ
Stem Cells 1993 Jul;11 Suppl 2:123-30. doi: 10.1002/stem.5530110820. PMID: 7691318

Prognosis

Kapralova K, Jahoda O, Koralkova P, Gursky J, Lanikova L, Pospisilova D, Divoky V, Horvathova M
Int J Mol Sci 2020 Dec 17;21(24) doi: 10.3390/ijms21249652. PMID: 33348919Free PMC Article
Vlachos A, Atsidaftos E, Lababidi ML, Muir E, Rogers ZR, Alhushki W, Bernstein J, Glader B, Gruner B, Hartung H, Knoll C, Loew T, Nalepa G, Narla A, Panigrahi AR, Sieff CA, Walkovich K, Farrar JE, Lipton JM
Pediatr Blood Cancer 2020 Dec;67(12):e28748. Epub 2020 Oct 6 doi: 10.1002/pbc.28748. PMID: 33025707Free PMC Article
Maisonneuve E, Ben M'Barek I, Leblanc T, Da Costa L, Friszer S, Pernot F, Thomas P, Castaigne V, Toly N'Dour C, Mailloux A, Cortey A, Jouannic JM
Fetal Diagn Ther 2020;47(2):156-164. Epub 2019 Sep 10 doi: 10.1159/000501554. PMID: 31505487
Kalejaiye A, Giri N, Brewer CC, Zalewski CK, King KA, Adams CD, Rosenberg PS, Kim HJ, Alter BP
Pediatr Blood Cancer 2016 Dec;63(12):2139-2145. Epub 2016 Jul 18 doi: 10.1002/pbc.26155. PMID: 27428025
Gillio AP, Faulkner LB, Alter BP, Reilly L, Klafter R, Heller G, Young DC, Lipton JM, Moore MA, O'Reilly RJ
Stem Cells 1993 Jul;11 Suppl 2:123-30. doi: 10.1002/stem.5530110820. PMID: 7691318

Clinical prediction guides

Gianferante MD, Wlodarski MW, Atsidaftos E, Da Costa L, Delaporta P, Farrar JE, Goldman FD, Hussain M, Kattamis A, Leblanc T, Lipton JM, Niemeyer CM, Pospisilova D, Quarello P, Ramenghi U, Sankaran VG, Vlachos A, Volejnikova J, Alter BP, Savage SA, Giri N
Haematologica 2021 May 1;106(5):1303-1310. doi: 10.3324/haematol.2020.246629. PMID: 32241839Free PMC Article
Kapralova K, Jahoda O, Koralkova P, Gursky J, Lanikova L, Pospisilova D, Divoky V, Horvathova M
Int J Mol Sci 2020 Dec 17;21(24) doi: 10.3390/ijms21249652. PMID: 33348919Free PMC Article
Kristiansson A, Gram M, Flygare J, Hansson SR, Åkerström B, Storry JR
Int J Mol Sci 2020 Sep 30;21(19) doi: 10.3390/ijms21197234. PMID: 33008134Free PMC Article
Wan Y, Chen X, An W, Ruan M, Zhang J, Chang L, Zhang R, Zhu S, Zhang Y, Yang W, Guo Y, Yuan W, Zou Y, Chen Y, Zhu X
Int J Hematol 2016 Oct;104(4):430-9. Epub 2016 Jun 21 doi: 10.1007/s12185-016-2044-9. PMID: 27329125
Buchanan GR, Alter BP, Holtkamp CA, Walsh EG
Pediatrics 1981 Aug;68(2):238-41. PMID: 7267232

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...