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PubMed This is a summary of 21 peer-reviewed journal articles Updated
Neurology

Imaging and Genetics: Confirming the Diagnosis

At a Glance

LCC is diagnosed by combining MRI findings of white matter changes and cysts with CT evidence of brain calcifications and, when needed, genetic testing for SNORD118; a negative exome test does not always rule it out.

Diagnosing Leukoencephalopathy with calcifications and cysts (LCC) relies on a characteristic pattern left in the brain. Doctors call this the imaging triad, a group of three distinct features that strongly suggest the condition, though they can overlap with other disorders like Coats plus syndrome or primary familial brain calcification [1][2]. Diagnosis requires integrating these imaging findings with your clinical history and genetic test results.

Because the features can be subtle or develop at different times, doctors typically use specialized imaging and genetic testing to confirm the diagnosis. The choice and repetition of these scans are individualized by your care team.

The Imaging Triad: What Doctors Look For

The three features of LCC are evaluated using MRI (magnetic resonance imaging) and CT (computed tomography) scans. Each tool provides a different piece of the puzzle [3][4].

1. Leukoencephalopathy (White Matter Disease)

This is best viewed on an MRI. The white matter acts as the brain’s communication network. In LCC, the MRI (specifically on T2 or FLAIR sequences) shows these areas as unusually bright or “hyperintense” [5][6].

  • Where it happens: It is usually found in the deep and periventricular (near the fluid-filled spaces) white matter [6].
  • Sparing the U-fibers: The very outer layer of white matter, called subcortical U-fibers, is often left healthy and unaffected [5].

2. Calcifications (Mineral Deposits)

While an MRI can sometimes hint at calcifications, a CT scan is exceptionally good at confirming them. On a CT, these deposits appear as bright, dense, bone-like spots [7][3].

  • Typical Locations: These are not random. They most often appear in the basal ganglia and thalami (central hubs of the brain) and the dentate nuclei (a part of the cerebellum responsible for coordination) [7][3].
  • Appearance: Doctors often describe them as “bulky” or “nodular” [7].

3. Cysts (Fluid-Filled Sacs)

Cysts are best characterized by MRI, which can show if they are filled with simple fluid or more complex material like blood [3][8].

  • Growth and Pressure: Cysts can be asymmetric (appearing on only one side) and vary wildly in size [6]. If a cyst grows large, it can cause mass effect, which means it pushes on the surrounding healthy brain tissue [9][10].
  • Evolution: Calcifications and white matter changes often appear years before a cyst is ever seen [11][12].

Minimizing Radiation

While CT scans are excellent for checking calcifications or acute hemorrhage, they involve ionizing radiation. To limit radiation exposure, especially in children, your doctors will likely favor MRI for routine long-term follow-up of white matter and cysts, reserving CT for specific diagnostic questions or urgent changes [13][14].

Why Genetic Testing Can Be Tricky

Because the imaging triad overlaps with other conditions, genetic testing for mutations in the SNORD118 gene is utilized to help confirm the diagnosis [1]. However, standard genetic tests often fail to find the problem.

The “Non-Coding” Challenge

Most standard genetic tests, like Whole-Exome Sequencing (WES), focus on the parts of your DNA that provide instructions for making proteins. However, SNORD118 is a non-coding gene. It creates a molecule called U8 snoRNA, which helps build cellular machinery rather than proteins [15][16]. Because WES often misses these non-coding regions, a person with LCC might receive a “normal” or “negative” result [17][18].

Finding the Right Test

To find SNORD118 mutations, doctors may need to use:

  • Whole-Genome Sequencing (WGS): WGS covers substantially more non-coding sequence than whole-exome sequencing, making it more likely to catch SNORD118 mutations. However, it still has limitations regarding coverage, structural or repeat variants, and difficult genomic regions, so it is not literally 100% complete [10][18].
  • Targeted Sequencing: This is a test specifically designed to look closely at the SNORD118 gene and its surrounding areas [19][20].

A negative WES or WGS result should not automatically exclude LCC if the imaging and clinical picture strongly point to it. A genetics professional can review any negative result to determine if additional testing is necessary [19][21].

Common questions in this guide

How do doctors diagnose leukoencephalopathy with calcifications and cysts?
Doctors look for an imaging pattern called the triad: white matter changes, brain calcifications, and fluid-filled cysts. MRI is especially useful for white matter changes and cysts, while CT is especially sensitive for calcifications. The diagnosis also considers symptoms, medical history, and genetic results.
What can an MRI show in LCC?
MRI can show changes in the brain’s white matter and identify cysts, including their size and whether they contain simple fluid or more complex material. It can also show whether a large cyst is pressing on nearby brain tissue. MRI is often preferred for routine follow-up because it does not use ionizing radiation.
Why might I need a CT scan after having an MRI for LCC?
CT is particularly good at detecting the mineral deposits that occur in LCC, especially in deep parts of the brain and the cerebellum. MRI is better for white matter changes and cysts, so the two scans provide different information. Your care team decides when CT is needed to limit radiation exposure.
Can a negative genetic test rule out LCC?
Not always. Whole-exome sequencing may miss changes in SNORD118 because this gene does not make a protein, and even whole-genome sequencing has technical limits. If the scans and clinical picture still suggest LCC, a genetics professional can review the result and consider targeted or additional testing.
Which genetic tests can find SNORD118 changes?
Whole-genome sequencing examines more of the DNA than whole-exome sequencing and may detect SNORD118 changes that an exome test misses. A targeted test can examine SNORD118 and nearby DNA more closely. Neither test detects every possible genetic change, so results must be interpreted with the imaging and clinical findings.
What symptoms could mean an LCC cyst is growing?
A growing cyst can press on nearby brain tissue, a problem called mass effect. New or worsening headaches, nausea, or balance changes may be important to report promptly, although these symptoms can have other causes. Contact your care team for advice about new or worsening symptoms.

Get notified when new evidence is published on Leukoencephalopathy with calcifications and cysts.

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References

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This page is for informational purposes only and does not constitute medical advice. Your care team and genetics professional should interpret your LCC scans and genetic results in context.

Guide contents Leukoencephalopathy with calcifications and cysts
Research & Literature
02 The Science Behind LCC 04 Navigating Symptoms and Urgent Warning Signs