Fanconi anemia differential diagnosis

Jump to navigation Jump to search

Fanconi anemia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Fanconi anemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Fanconi anemia differential diagnosis On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Fanconi anemia differential diagnosis

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Fanconi anemia differential diagnosis

CDC on Fanconi anemia differential diagnosis

Fanconi anemia differential diagnosis in the news

Blogs on Fanconi anemia differential diagnosis

Directions to Hospitals Treating Fanconi anemia

Risk calculators and risk factors for Fanconi anemia differential diagnosis

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.

Template:WH Template:WS