Fanconi anemia differential diagnosis: Difference between revisions

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{{Fanconi anemia}}
{{Fanconi anemia}}


{{CMG}}; {{AE}}  
{{CMG}}; {{AE}} {{shyam}}


==Overview==
==Overview==
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
Fanconi anemia must be differentiated from [[aplastic anemia]], [[paroxysmal nocturnal hemoglobinuria]], chromosomal breakage syndromes, and hereditary bone marrow failure syndromes ([[dyskeratosis congenita]] and other short telomere syndromes). Each disease has a different pathophysiology, exam findings, and histopathology.


OR
==Differentiating Fanconi anemia from other diseases==
*Fanconi anemia must be differentiated from other diseases (as noted below).<ref name="pmid24237973">{{cite journal| author=Hartung HD, Olson TS, Bessler M| title=Acquired aplastic anemia in children. | journal=Pediatr Clin North Am | year= 2013 | volume= 60 | issue= 6 | pages= 1311-36 | pmid=24237973 | doi=10.1016/j.pcl.2013.08.011 | pmc=3894991 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24237973  }}</ref><ref name="pmid27069254">{{cite journal| author=Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al.| title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. | journal=Blood | year= 2016 | volume= 127 | issue= 20 | pages= 2391-405 | pmid=27069254 | doi=10.1182/blood-2016-03-643544 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27069254  }}</ref>


[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
===Differential Diagnosis===
 
{| class="wikitable sortable mw-collapsible"
==Differentiating X from other Diseases==
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
*[Disease name] must be differentiated from [differential dx1], [differential dx2], and [differential dx3].
 
*As [disease name] manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. [Subtype name 1] must be differentiated from other diseases that cause [clinical feature 1], such as [differential dx1] and [differential dx2]. In contrast, [subtype name 2] must be differentiated from other diseases that cause [clinical feature 2], such as [differential dx3] and [differential dx4].
 
===Preferred Table===
{|
|+
|+
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Diseases
| colspan="3" rowspan="2" |'''Clinical manifestations'''
| colspan="6" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Clinical manifestations'''
| rowspan="3" |Pathophysiology
! colspan="7" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para-clinical findings
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Para-clinical findings
| colspan="1" rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Gold standard'''
| colspan="1" rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Gold standard'''
! rowspan="4" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Additional findings
! rowspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Additional findings
|-
|-
| colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |'''Symptoms'''
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings
! colspan="3" rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical examination
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology
|-
|-
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab Findings
|Disease
! colspan="3" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptom  
! rowspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Histopathology
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical exam  
|-
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Blood profile
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptom 1
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Anamalies
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptom 2
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Symptom 3
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical exam 1
! colspan="1" rowspan="1" style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical exam 2
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Physical exam 3
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab 1
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab 2
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Lab 3
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging 1
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging 2
! style="background: #4479BA; color: #FFFFFF; text-align: center;" |Imaging 3
|-
|-
|Fanconi Anemia
|Fanconi Anemia
|
|Short stature, delicate features, upper limbs absent or hypoplastic thumbs, supernumerary, bifid clinodactyly
|
infection, petechia, pallor
|
|Skin – Generalized hyperpigmentation; hypopigmented areas; large freckles, café-au-lait spots
|Skin – Generalized hyperpigmentation; hypopigmented areas; large freckles, café-au-lait spots
|Short stature, delicate features, upper limbs absent or hypoplastic thumbs, supernumerary, bifid clinodactyly
Head – Microcephaly or hydrocephaly; birdlike face, mid-face hypoplasia, Sprengel's deformity of neck,
|Head – Microcephaly or hydrocephaly; birdlike face, mid-face hypoplasia, Sprengel's deformity of neck,  
 
Eyes- Microphthalmia, ptosis, epicanthal folds, strabismus
Eyes- Microphthalmia, ptosis, epicanthal folds, strabismus
|Cytopenia, Bone marrow failure
|Inherited defect in DNA Repair causes loss of HSC that leads to bone marrow failure.
|
|Anemia: normocellular or hypercellular bone marrow
|
|Gastrointestinal  Atresias, imperforate anus, TE fistula, malrotation,
|
|Gastrointestinal anomalies – Atresias, imperforate anus, tracheoesophageal fistula, malrotation,


Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis
Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis
|Cardiopulmonary anomalies – Congenital heart disease (patent ductus arteriosus, atrial or ventricular septal defects, coarctation, situs inversus)
|
|
|FA gene sequencing   
|FA gene sequencing   
|Incrreased chromosomal breakage in response to mitomycin C or diepoxybutane (quite sensitive but not entirely specific)
|Increased chromosomal breakage in response to mitomycin C or diepoxybutane (quite sensitive but not entirely specific)
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Acquired Aplastic Anemia
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Acquired Aplastic Anemia
| style="background: #F5F5F5; padding: 5px;" |recurrent infections due to neutropenia, mucosal hemorrhage or menorrhagia due to thrombocytopenia, or fatigue and cardiopulmonary findings associated with progressive anemia.
| style="background: #F5F5F5; padding: 5px;" |Infections, mucosal hemorrhage, menorrhagia  
| style="background: #F5F5F5; padding: 5px;" |infections including bacterial and fungal in cases of severe neutropenia
| style="background: #F5F5F5; padding: 5px;" |Pallor and petechiae
| style="background: #F5F5F5; padding: 5px;" |
The liver, spleen, and lymph nodes are typically enlarged in AA, if its enlarged it may suggest alternative diagnosis
| style="background: #F5F5F5; padding: 5px;" |especially pallor and petechiae.
|No known causes 70% cases, known cases are caused by drugs, virus, radiation
| style="background: #F5F5F5; padding: 5px;" |The liver, spleen, and lymph nodes are typically enlarged in AA, if its enlarged it may suggest alternative diagnosis.
| style="background: #F5F5F5; padding: 5px;" |Anemia
| style="background: #F5F5F5; padding: 5px;" |
normocellular or hypercellular bone marrow
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |Gastrointestinal  Atresias, imperforate anus, TE fistula, malrotation,
| style="background: #F5F5F5; padding: 5px;" |Serum chemistries, including electrolytes, liver function tests (including lactate dehydrogenase [LDH]), and renal function tests should be performed, Also serum B12 and Folate should be performed to exclude
 
| style="background: #F5F5F5; padding: 5px;" |
Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |Bone marrow aspiration and Biopsy= hypocellular bone marrow in the absence of an abnormal infiltrate or marrow fibrosis.
| style="background: #F5F5F5; padding: 5px;" |Hypocellular bone marrow  
| style="background: #F5F5F5; padding: 5px;" |typically a more rapid onset and progression of cytopenias; and a response to immunosuppressive therapy
| style="background: #F5F5F5; padding: 5px;" |Rapid onset
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Paroxysmal nocturnal hemoglobinuria (PNH)
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Paroxysmal nocturnal hemoglobinuria (PNH)
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●Hemoglobinuria  
●Hemoglobinuria  
| style="background: #F5F5F5; padding: 5px;" |Abdominal pain  
 
Abdominal pain  


●Bone marrow suppression
●Bone marrow suppression


●Erectile dysfunction  
●Erectile dysfunction  
| style="background: #F5F5F5; padding: 5px;" |Chest pain  
 
●Chest pain  


●Thrombosis  
●Thrombosis  
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●Renal insufficiency  
●Renal insufficiency  
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|Acquired mutation in PIGA gene --> problem in synthesis of
DGI ---> complement mediated Intravascular hemolysis
| style="background: #F5F5F5; padding: 5px;" |Anemia
normocellular or hypercellular bone marrow
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |●Hypo/Hyper
/Normo
cellular,
| style="background: #F5F5F5; padding: 5px;" |Flow cytometry
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |Anemia
|-
●Increased reticulocyte count
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Other inherited bone marrow failure syndromes
(Dyskeratosis congenita and other short telomere syndromes)
| style="background: #F5F5F5; padding: 5px;" |'''Bone marrow failure'''
 
Classic mucocutaneous and additional dermatologic findings
 
•Skin dyspigmentation
 
•Nail irregularities
 
•Leukoplakia
 
•Premature graying/hair loss
 
•Hyperhidrosis – 15 percent
 
●Ophthalmologic/Epiphora
 
 (excessive tearing/lacrimal duct stenosis)
 
●Neurologic/Cognitive
 
•Developmental delay
 
•Ataxia/cerebellar hypoplasia – approximately
 
•Microcephaly
 
●Pulmonary disease (pulmonary fibrosis)
 
●Endocrine/Growth/Urologic 
 
features
 
•Short stature
 
•Intrauterine growth retardation
 
•Hypogonadism/Undescended
 
 testes
 
•Urethral stricture/phimosis 
 
•Osteoporosis and related complications
| style="background: #F5F5F5; padding: 5px;" |Unlike Fanconi anemia, individuals with DC do not appear to have impaired fertility


●Increased lactate dehydrogenase (LDH) and bilirubin
●Dental manifestations (caries)  


●Decreased haptoglobin
●Gastroenterologic/Hepatologic 


●Free serum hemoglobin with pink/red serum
manifestations


'''Bone Marrow''': PNH usually have a normocellular or hypercellular bone marrow with erythroid hyperplasia. Stainable iron is often absent
•Esophageal strictures
| style="background: #F5F5F5; padding: 5px;" |hemolytic anemia (indirect hyperbiliribinemia)
 Intravascular hemolysis in PNH can lead to [[ARF]] and [[Chronic renal disease|CRD]].
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
●Hemoglobinuria with pink/red urine, positive dipstick for heme, and negative sediment for red blood cells


●Negative direct antiglobulin (Coombs) test (DAT)
•Liver disease (cirrhosis, fibrosis) or gastroenteropathy


●Hypocellular, normocellular or hypercellular bone marrow, often with erythroid hyperplasia; erythroid dysplasia is not uncommon
●Cancer
|(DC) and  telomere related disorders, mutations in genes that maintain telomere length in rapidly dividing cells that lead to premature cell death, senescence, or genomic instability, which in turn results


●Findings of iron deficiency may be seen in some patients due to excessive iron loss from hemoglobinuria and hemosiderinuria (eg, low iron, low ferritin, increased transferrin, absent bone marrow iron
in impaired function and cellular homeostasis in many organs and tissues.
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |Reticular dysgenesis
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |'''FLAER''': Flow cytometry detect (GPI) anchored proteins, which are reduced or absent on blood cells in PNH.
Acquired mutations in the ''PIGA'' gene result in the dominance of a hematopoietic progenitor cell clone lacking glycosylphosphatidylinositol (GPI) anchors
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
| style="background: #F5F5F5; padding: 5px;" |Flow cytometry
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Other inherited bone marrow failure syndromes
| style="background: #F5F5F5; padding: 5px;" | - chromosomal breakage test.
| style="background: #F5F5F5; padding: 5px;" |Transient pancytopenia and bone marrow hypoplasia may be caused by a number of exposures including medications, chemicals, certain viral infections, and sepsis or other severe bacterial infections.
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
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| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |negative chromosomal breakage test.
|- style="background: #4479BA; color: #FFFFFF; text-align: center;"
!Diseases
!Symptom 1
! colspan="1" rowspan="1" |Symptom 2
!Symptom 3
!Physical exam 1
! colspan="1" rowspan="1" |Physical exam 2
!Physical exam 3
!Lab 1
!Lab 2
!Lab 3
!Imaging 1
!Imaging 2
!Imaging 3
!Histopathology
|'''Gold standard'''
!Additional findings
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Drug-induced or infection-associated pancytopenia
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Drug-induced or infection-associated pancytopenia
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
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|
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| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Rare chromosomal breakage syndromes
| style="background: #DCDCDC; padding: 5px; text-align: center;" |Rare syndromes,
| style="background: #F5F5F5; padding: 5px;" |
Nijmegen breakage
| style="background: #F5F5F5; padding: 5px;" |
 
| style="background: #F5F5F5; padding: 5px;" |
syndrome (''NBS''),
| style="background: #F5F5F5; padding: 5px;" |
 
| style="background: #F5F5F5; padding: 5px;" |
Bloom syndrome
| style="background: #F5F5F5; padding: 5px;" |
 
| style="background: #F5F5F5; padding: 5px;" |
(''BLM''), ataxia
| style="background: #F5F5F5; padding: 5px;" |
 
| style="background: #F5F5F5; padding: 5px;" |
telangiectasia
| style="background: #F5F5F5; padding: 5px;" |
 
| style="background: #F5F5F5; padding: 5px;" |
(''ATM''), LIG4
| style="background: #F5F5F5; padding: 5px;" |
 
| style="background: #F5F5F5; padding: 5px;" |
syndrome (''LIG4''),
 
NHEJ1 deficiency
 
(''NHEJ1''), Seckel syndrome ''(ATR)'',
 
'' ''cohesinopathies
 
Roberts
 
syndrome (''ESCO2'')
 
Warsaw
 
breakage syndrome (''DDX11'').
| style="background: #F5F5F5; padding: 5px;" |Microcephaly, short stature increased
malignancy
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|NBS: chromosomal instability disorder  caused by mutations in the nibrin ''(NBN)'' gene
DNA breaks are not efficiently repaired in the absence of fibrin.
oxidative/alkylating stress damages the cells
| style="background: #F5F5F5; padding: 5px;" |No specific findings
| style="background: #F5F5F5; padding: 5px;" |Gastrointestinal  Atresias, imperforate anus, TE fistula, malrotation,
Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |Abnormal chromosomal breakage test
| style="background: #F5F5F5; padding: 5px;" |No bone marrow
failure
|-
|-
| style="background: #DCDCDC; padding: 5px; text-align: center;" |De novo myelodysplastic syndrome (MDS)
| style="background: #DCDCDC; padding: 5px; text-align: center;" |De novo myelodysplastic syndrome (MDS)
| style="background: #F5F5F5; padding: 5px;" |MDS can arise de novo or secondary to another bone marrow disorder
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
|
| style="background: #F5F5F5; padding: 5px;" |Bone marrow failure
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |Positive
chromosomal breakage tests
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |
| style="background: #F5F5F5; padding: 5px;" |Negative chromosomal breakage tests
| style="background: #F5F5F5; padding: 5px;" |
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|}
|}


Latest revision as of 16:49, 4 May 2019

Fanconi anemia Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shyam Patel [2]

Overview

Fanconi anemia must be differentiated from aplastic anemia, paroxysmal nocturnal hemoglobinuria, chromosomal breakage syndromes, and hereditary bone marrow failure syndromes (dyskeratosis congenita and other short telomere syndromes). Each disease has a different pathophysiology, exam findings, and histopathology.

Differentiating Fanconi anemia from other diseases

  • Fanconi anemia must be differentiated from other diseases (as noted below).[1][2]

Differential Diagnosis

Clinical manifestations Pathophysiology Para-clinical findings Gold standard Additional findings
Lab Findings Imaging Histopathology
Disease Symptom Physical exam Blood profile Anamalies
Fanconi Anemia Short stature, delicate features, upper limbs absent or hypoplastic thumbs, supernumerary, bifid clinodactyly

infection, petechia, pallor

Skin – Generalized hyperpigmentation; hypopigmented areas; large freckles, café-au-lait spots

Head – Microcephaly or hydrocephaly; birdlike face, mid-face hypoplasia, Sprengel's deformity of neck,

Eyes- Microphthalmia, ptosis, epicanthal folds, strabismus

Inherited defect in DNA Repair causes loss of HSC that leads to bone marrow failure. Anemia: normocellular or hypercellular bone marrow Gastrointestinal  Atresias, imperforate anus, TE fistula, malrotation,

Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis

FA gene sequencing Increased chromosomal breakage in response to mitomycin C or diepoxybutane (quite sensitive but not entirely specific)
Acquired Aplastic Anemia Infections, mucosal hemorrhage, menorrhagia Pallor and petechiae

The liver, spleen, and lymph nodes are typically enlarged in AA, if its enlarged it may suggest alternative diagnosis

No known causes 70% cases, known cases are caused by drugs, virus, radiation Anemia

normocellular or hypercellular bone marrow

Gastrointestinal  Atresias, imperforate anus, TE fistula, malrotation,

Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis

Hypocellular bone marrow Rapid onset
Paroxysmal nocturnal hemoglobinuria (PNH) Fatigue

●Dyspnea

●Hemoglobinuria

Abdominal pain

●Bone marrow suppression

●Erectile dysfunction

●Chest pain

●Thrombosis

●Renal insufficiency

Acquired mutation in PIGA gene --> problem in synthesis of

DGI ---> complement mediated Intravascular hemolysis

Anemia

normocellular or hypercellular bone marrow

●Hypo/Hyper

/Normo

cellular,

Flow cytometry
Other inherited bone marrow failure syndromes

(Dyskeratosis congenita and other short telomere syndromes)

Bone marrow failure

Classic mucocutaneous and additional dermatologic findings

•Skin dyspigmentation

•Nail irregularities

•Leukoplakia

•Premature graying/hair loss

•Hyperhidrosis – 15 percent

●Ophthalmologic/Epiphora

 (excessive tearing/lacrimal duct stenosis)

●Neurologic/Cognitive

•Developmental delay

•Ataxia/cerebellar hypoplasia – approximately

•Microcephaly

●Pulmonary disease (pulmonary fibrosis)

●Endocrine/Growth/Urologic 

features

•Short stature

•Intrauterine growth retardation

•Hypogonadism/Undescended

 testes

•Urethral stricture/phimosis 

•Osteoporosis and related complications

Unlike Fanconi anemia, individuals with DC do not appear to have impaired fertility

●Dental manifestations (caries)

●Gastroenterologic/Hepatologic 

manifestations

•Esophageal strictures

•Liver disease (cirrhosis, fibrosis) or gastroenteropathy

●Cancer

(DC) and telomere related disorders, mutations in genes that maintain telomere length in rapidly dividing cells that lead to premature cell death, senescence, or genomic instability, which in turn results

in impaired function and cellular homeostasis in many organs and tissues.

Reticular dysgenesis Flow cytometry - chromosomal breakage test.
Drug-induced or infection-associated pancytopenia
Rare syndromes,

Nijmegen breakage

syndrome (NBS),

Bloom syndrome

(BLM), ataxia

telangiectasia

(ATM), LIG4

syndrome (LIG4),

NHEJ1 deficiency

(NHEJ1), Seckel syndrome (ATR),

 cohesinopathies

Roberts

syndrome (ESCO2)

Warsaw

breakage syndrome (DDX11).

Microcephaly, short stature increased

malignancy

NBS: chromosomal instability disorder caused by mutations in the nibrin (NBN) gene

DNA breaks are not efficiently repaired in the absence of fibrin.

oxidative/alkylating stress damages the cells

No specific findings Gastrointestinal  Atresias, imperforate anus, TE fistula, malrotation,

Kidney – Abnormal, ectopic, horseshoe, hypoplastic, or absent kidney; hydronephrosis

Abnormal chromosomal breakage test No bone marrow

failure

De novo myelodysplastic syndrome (MDS) MDS can arise de novo or secondary to another bone marrow disorder Bone marrow failure Positive

chromosomal breakage tests

Negative chromosomal breakage tests

References

  1. ↑ Hartung HD, Olson TS, Bessler M (2013). "Acquired aplastic anemia in children". Pediatr Clin North Am. 60 (6): 1311–36. doi:10.1016/j.pcl.2013.08.011. PMC 3894991. PMID 24237973.
  2. ↑ Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM; et al. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–405. doi:10.1182/blood-2016-03-643544. PMID 27069254.

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