Diagnosis and Testing Results
At a Glance
Andermann syndrome is confirmed mainly through genetic testing that finds disease-causing or likely disease-causing variants in both copies of SLC12A6. MRI and nerve studies add important clues, but a normal MRI or an early near-normal test does not rule it out.
Confirming a diagnosis of Andermann syndrome is a multi-step process that looks at how the brain is structured, how the nerves are functioning, and the specific genetic “blueprint” of the child. Because the syndrome can look different from one person to another, doctors use a combination of imaging, electrical tests, and genetic sequencing to get a complete picture.
Brain MRI: The “Bridge” Scan
A Brain MRI (Magnetic Resonance Imaging) uses strong magnets and radio waves to create a detailed map of the brain. In Andermann syndrome, doctors look specifically at the corpus callosum, the bundle of fibers connecting the brain’s two halves [1].
Findings on an MRI can vary significantly:
- Agenesis: The corpus callosum is completely missing [2].
- Hypoplasia or Dysgenesis: The corpus callosum is present but is underdeveloped, unusually thin, or malformed [3][1].
- Normal-Appearing: It is important to know that some children with a confirmed genetic diagnosis have a completely intact and normal corpus callosum [3][4]. A normal brain scan does not rule out Andermann syndrome if other symptoms and genetic tests align.
Electrophysiology: Nerve Function Testing
To understand how well the “wiring” in your child’s body is working, specialists use two related tests, which should be interpreted by a pediatric neuromuscular specialist [5].
- Nerve Conduction Studies (NCS) measure the latency (delay), conduction velocity (speed), and amplitude (signal strength) of electrical signals as they travel through peripheral nerves.
- Electromyography (EMG) evaluates the electrical activity directly within the muscles, often using a small needle examination.
These tests can show complex and variable findings. While Andermann syndrome is often described as a severe sensorimotor axonal neuropathy (meaning the core of the nerve fiber, or axon, is affected, causing low amplitude), demyelinating features (damage to the myelin coating, causing low velocity) are also reported [4][6][7]. Importantly, low velocity alone does not automatically prove demyelination, as age, limb temperature, and technical factors play a role. In very young infants, these tests can sometimes appear near-normal early on; an early near-normal study does not rule out the disease [3].
Genetic Testing: The Definitive Confirmation
While MRI and nerve tests provide important clues, molecular genetic testing is the definitive way to confirm a diagnosis. This is usually done through tests like Whole Exome Sequencing (WES) or a targeted genetic panel [8][9].
For a diagnosis of classic Andermann syndrome, the report generally requires:
- Biallelic Variants: This means there are pathogenic or likely pathogenic variants on both copies of the SLC12A6 gene [3][4].
- Inheritance Pattern (Phase): When two different variants are found, doctors usually test both parents to confirm the variants are in trans. This means one mutation was inherited from the mother and the other from the father [3][10].
If a lab report shows only one pathogenic variant, it does not confirm the disease, nor does it immediately confirm dominant neuropathy or simple carrier status. A second variant may have been missed due to test limitations (like a large deletion or structural change), requiring copy-number analysis or deletion/duplication testing.
Understanding Your Lab Report
Genetic reports use specific technical language. Here is what those terms mean:
- Pathogenic / Likely Pathogenic: The genetic change is known to cause disease or is very likely to do so [10].
- Variant of Uncertain Significance (VUS): A change was found, but there isn’t enough scientific data yet to know if it causes the condition. A VUS neither confirms nor excludes the disease and should not be used alone to predict prognosis, change treatment, or make reproductive decisions [9]. Genetic classifications can change over time, and VUS results may be reanalyzed in the future.
- Compound Heterozygous: This means the two variants on the SLC12A6 gene are different from each other, whereas homozygous means both variants are identical [3][4].
Common questions in this guide
How is Andermann syndrome diagnosed?
Can a normal brain MRI rule out Andermann syndrome?
What do nerve conduction studies and EMG show in Andermann syndrome?
What does it mean if SLC12A6 variants are in trans?
What if genetic testing finds only one pathogenic SLC12A6 variant?
What does a variant of uncertain significance mean?
One line in your results can change your plan.
A lab report with a single pathogenic SLC12A6 variant may still need copy-number testing to look for a second. We check your results against the latest research to help you prepare for what’s next.
Get notified when new evidence is published on Corpus callosum agenesis-neuronopathy syndrome.
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References
References (10)
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PMID: 31639835 - 6
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PMID: 37173814 - 10
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PMID: 25741868
This page explains how Andermann syndrome is evaluated, including MRI, nerve studies, and SLC12A6 testing, for educational purposes only and does not constitute medical advice. A qualified pediatric neurology, neuromuscular, or genetics professional should interpret your child's results.