How Fanconi Anemia Is Diagnosed

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Fanconi anemia (FA) is a rare genetic disorder that affects young children, but often they are asymptomatic early in life.

Clinical manifestations of FA can develop over time and involve many organ systems. Clinical suspicion of FA is mostly based on physical defects at birth (such as a heart defect or malformed hands or arms), as well as delays in growth.

Later in life, between 5 and 10 years of age, children with FA often develop life-threatening bone marrow failure, which may cause symptoms that include fatigue, easy bruising, frequent infections, and bleeding from the gums or nose.

Because symptoms are highly variable and many FA symptoms overlap with those observed in other syndromes, making a reliable diagnosis based on clinical features is virtually impossible. The most common method to diagnose FA is to extract blood and test it for chromosomal breakage.

This article will discuss the chromosomal breakage test and other tests that may be used in the diagnosis of FA.

Scientist testing blood

krisanapong detraphiphat / Getty Images

Physical Examination

Evaluation for Fanconi anemia usually begins with a review of the person’s medical history and their family history, asking about current symptoms, and doing a complete physical. Children are mainly affected by FA so a parent will usually answer questions during the evaluation. 

A medical history that takes your family history and signs and symptoms into account, and a focused physical exam looking for dark spots called café au lait spots are central to making an accurate diagnosis of FA.

Keen observation of common physical examination findings for aplastic anemia may also raise a healthcare provider’s clinical suspicion of FA. These findings include:

  • Short stature
  • Dyspnea (shortness of breath)
  • Petechiae (tiny purple-brown spots due to bleeding under the skin)
  • Ecchymosis (generalized discoloration from a bruise, or bleeding under the skin)
  • Jaundice (yellowing of the skin and whites of the eyes)
  •  Pallor (sickly paleness)

Recap

During a physical exam, a healthcare provider will take a family and medical history and look for physical signs of FA, including café au lait spots, delayed growth and development, and symptoms of anemia, such as fatigue, shortness of breath, and easy bruising.

Labs and Tests

The most common test for FA is a blood test called a chromosomal breakage (CB) test. It tests for genomic instability (the increased tendency for DNA mutations to occur during cell division)—a hallmark characteristic of FA.

During a CB test, blood is exposed to one of three DNA cross-linking agents that FA patients are hypersensitive to. If there is evidence of chromosomal breakage after exposure, a diagnosis of FA can be made.

Prenatal diagnosis is feasible with a CB test on fetal blood or, when the mutation is known, by genetic testing. The CB test can also be done on an infant's blood sample after birth.

Everyone who receives an FA diagnosis should be referred to a hematologist (a doctor specializing in blood disorders) with expertise in FA for medical monitoring and management.  

FA Complementation Types

After an FA diagnosis is made, your hematologist may want to determine your FA complementation group to help guide medical management and inform future treatment decisions

Complementation group testing is used to classify patients with FA according to the specific gene defects that cause FA. Additional blood tests can identify specific alterations in your DNA.

A complete blood cell count (CBC) will also need to be taken since FA typically involves some bone marrow dysfunction. Concerns related to the blood and marrow most commonly include:

If one or more blood cell types are low, a bone marrow biopsy (where a sample of bone marrow is removed using a hollow needle and sent to a lab for testing) may be suggested.

An electrocardiogram (ECG) may be used to detect heart rhythm abnormalities, which can indicate a heart defect.

To establish the extent of disease in an individual diagnosed with FA, the following evaluations are recommended, as needed:

  • Ultrasound examination of the kidneys and urinary tract
  • Formal hearing test (audiology examination)
  • Developmental assessment
  • Referral to necessary specialists, as needed 

Additional recommended exams include:

  • Ophthalmology examination to assess vision
  • Otolaryngology examination for head and neck cancer starting around age 10
  • Gynecological examinations at the appropriate age

Recap

The most common test for FA is a blood test called a chromosomal breakage test. Once a diagnosis of FA has been made, additional testing, including a CBC test, ECG, and exams with specialists, may be done to determine the extent and progression of the disease.

Imaging

Patients with Fanconi anemia have a higher incidence of central nervous system (CNS) abnormalities—especially in the posterior fossa (small space in the skull), corpus callosum (bundle of nerve fibers connecting the brain’s hemispheres), and pituitary gland (small endocrine gland at the base of the brain that regulates many body functions)—than those who do not have the disease. To assess for these abnormalities, your healthcare provider may order magnetic resonance imaging (MRI) on the brain.

FA can affect almost any organ in the body and is frequently associated with congenital (at-birth) abnormalities. Due to this, a computed tomography (CT) scan or MRI imaging of the entire body may also be performed. These images may show physical or organ defects, including:

  • Thumb and arm anomalies, such as extra, misshaped, or missing thumbs and fingers or an incompletely developed or missing radius (one of the forearm bones)
  • Skeletal anomalies of the hips, spine, or ribs
  • Structural kidney defects, like horseshoe kidneys, or absent kidneys
  • Small reproductive organs in males
  • Defects in tissues separating the heart

Ultrasound may also so be used to look for malformations of the urinary tract in men and women. Pelvic ultrasound may be used to assess malformation of the reproductive tract in women.

Recap

Imaging studies are mainly used after diagnosis to determine the extent of the disease. Imaging tests may include brain MRI, CT scan, full body MRI, and ultrasound.

Differential Diagnosis

The wide variability in how FA presents in individuals makes an accurate diagnosis based on symptoms alone difficult. Therefore, diagnosis of FA is often delayed until a patient develops bone marrow failure (BMF) or malignancies. 

FA should be considered in the differential diagnosis of all young patients with bone marrow failure (BMF) of unknown etiology (origin). Other cancer predisposition syndromes—such as Bloom syndrome, Rothmund-Thomson syndrome, or Werner syndrome—or other syndromes that raise the risk of congenital or acquired BMF must also be ruled out.

Other conditions that can cause symptoms of anemia, congenital malformations, and/or BMF include:

Summary

Fanconi anemia is mainly diagnosed with a specialized blood test called a chromosomal breakage test. If FA is suspected, this test can be done before birth with fetal blood, or after birth.

Once FA is confirmed, your healthcare provider will refer you and your child to a hemotologist (a doctor specializing in blood disorders). You or your child will also undergo additional testing, including blood work, a physical exam, and imaging studies to determine the extent of the disease. This will help your healthcare team decide how best to manage the condition going forward.

A Word From Verywell

Getting an early and accurate diagnosis for Fanconi anemia (FA) is often difficult because FA is highly variable, both genetically and in how it presents in each individual.

In other words, young children with FA have wide variations of disease, and one case may look totally different from the next. As a result, diagnosis in many cases can be delayed until bone marrow failure or cancer (leukemia) occurs. Therefore, delayed diagnosis or misdiagnosis, with incorrect treatments ordered, is not an uncommon event.

If FA runs in your family or you suspect your child may have the condition, don't delay in seeking out a trusted healthcare provider and advocating for chromosomal breakage testing to confirm a diagnosis. This will help start your family on the right path for monitoring and managing the disease and finding the support you need.

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