A brain MRI found something unexpected. Or a family member had one too. Understanding the genetic cause turns an uncertain finding into a clear surveillance plan.
Whole genome sequencing identifies KRIT1, CCM2, and PDCD10 variants — enabling MRI surveillance protocols and informed neurosurgical planning for you and your family.
Cerebral Cavernous Malformations
Cerebral cavernous malformations (CCM) are abnormal clusters of dilated blood vessels in the brain predisposed to hemorrhage. Familial CCM (approximately 50% of cases) follows autosomal dominant inheritance; the remaining cases involve single sporadic lesions. CCM manifests with hemorrhagic stroke, seizures, and progressive neurological deficits ranging from mild cognitive changes to severe disability. Hemorrhage rate for familial forms is approximately 0.7–1.1% per lesion per year. Three genes cause familial CCM: KRIT1 (encoding a scaffolding protein), CCM2, and PDCD10 (programmed cell death 10, an apoptosis-related protein). These proteins form the CCM complex regulating endothelial cell-cell adhesion and barrier function.
Familial CCM prevalence is estimated at 1 in 5,000 to 1 in 10,000 in Hispanic Americans due to founder mutation effects. KRIT1 mutations account for approximately 50% of familial CCM; CCM2 accounts for a minority; PDCD10 accounts for approximately 20% but is associated with a markedly more severe phenotype. Critically, PDCD10 mutations are associated with significantly more aggressive disease: earlier age of onset, greater number of lesions, higher hemorrhage rate, and additional manifestations including scoliosis and perioral skin lesions. Approximately 80% of carriers of a familial CCM variant develop detectable lesions by adulthood. Approximately 10–20% of familial CCM cases remain genetically unresolved, suggesting additional undiscovered genes.
A pathogenic variant in KRIT1, CCM2, or PDCD10 confirms familial CCM and mandates surveillance of all first-degree relatives with brain MRI — approximately 80% of carriers develop detectable lesions by adulthood. Genotype-phenotype correlation is critical: PDCD10-positive families should expect more aggressive disease with earlier onset, more lesions, higher hemorrhage risk, and additional systemic manifestations. These patients require closer neuroradiologic surveillance and lower thresholds for surgical intervention. Symptomatic CCM lesions (those causing seizures or hemorrhage) warrant neurosurgical evaluation; asymptomatic superficial lesions may be monitored conservatively. Genetic diagnosis enables genetic counseling and cascade family screening, identifying at-risk presymptomatic carriers who benefit from surveillance protocols.
PDCD10 mutations cause significantly more aggressive disease with earlier onset, greater lesion burden, higher hemorrhage rates, and additional systemic manifestations like scoliosis and perioral skin changes.
CCM genetic testing is underutilized despite high value for family surveillance. 10–20% of familial cases remain genetically unresolved, suggesting additional genes.
Genetic testing distinguishes familial CCM from sporadic lesions — critical for family surveillance
CCM genetic testing targeting the three major genes is available through specialized neurology genetic panels, but many centers do not routinely offer it — resulting in significant underdiagnosis of familial disease. Approximately 10–20% of familial CCM cases remain genetically unresolved despite comprehensive testing, suggesting additional undiscovered genes. Genetic testing is critical for distinguishing familial disease (requiring surveillance of at-risk relatives) from truly sporadic lesions. A single patient with a pathogenic variant implies that approximately 50% of first-degree relatives carry the variant and should receive surveillance MRI. Whole genome sequencing enables simultaneous evaluation of all three major genes and potential novel genes.
Genotype predicts disease severity and family screening urgency
A pathogenic variant in KRIT1, CCM2, or PDCD10 confirms familial CCM and mandates family cascade screening with brain MRI. Genotype-phenotype correlation is critical: PDCD10-positive families should expect significantly more aggressive disease with earlier symptom onset, greater lesion burden, and higher hemorrhage rates — warranting more intensive surveillance and lower thresholds for surgical intervention. KRIT1 and CCM2 families typically show milder disease courses. Approximately 80% of carriers develop detectable lesions by adulthood. Early detection through surveillance enables identification of lesions before hemorrhage occurs, preventing catastrophic neurological events.
Your full DNA (not just a part of it)
Traditional genetic testing looks at narrow sets of genes, missing most parts of your genome. We sequence your full genome — every gene and every region between genes.
Comprehensive insights and specialized reports
Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
Your test becomes more valuable every year
Your DNA does not change, but genome science is accelerating. Every month, new variant-disease associations are discovered. We validate these findings and update your reports automatically. Your test becomes more valuable every year.
The results doctors bring to their hardest cases.
Forty years of uncertainty. One test.
A patient had spent decades in the UK healthcare system without a diagnosis. Dante data, accepted by NHS clinical teams at Queen Elizabeth University Hospital Glasgow, identified Noonan Syndrome and a RUNX1 leukemia-associated variant that had gone undetected. After 40 years, they finally had an answer.
A complete read delivers a complete picture.
A patient came to Dante to investigate periodic paralysis. Reading the complete genome identified a concurrent hereditary cardiac finding — Brugada syndrome — that their doctor confirmed with an ECG. The result also explained a family member's unresolved cardiac history. One test. Every answer in it.
Sequenced in 2019. The data worked in 2021.
Jennifer sequenced her genome with Dante two years before her breast cancer diagnosis. When treatment began, Dante's pharmacogenomics data showed her prescribed chemotherapy would cause serious adverse effects. Her doctor selected an alternative — and she started effective treatment from day one.
Every genetic question deserves a complete answer.
Whether you are searching for answers today or protecting your health for tomorrow, a complete read of your entire genome is the only place to start.
It runs in your family. Now you can know if it runs in your genes.
Your genome contains inherited variants associated with medical conditions like cardiac, cancer, and neurological. We read all of them — with the clinical depth to give the result meaning.
Learn more →When traditional lab tests say you're fine. And you know you're not.
Standard diagnostic tests check for a pre-selected set of answers. We sequence your full DNA — including parts that no test was designed to check. If the answer is in your genome, we will help you find it.
Learn more →Your diagnosis may be right. Your treatment plan may be incomplete.
Your genes determine which treatments are most likely to work — and which are not. We give your doctor the tools and insights to inform your treatment plan.
Learn more →You want to know before something forces the question.
Some people don't wait for a diagnosis or a family history to act. Whole genome sequencing gives you the complete genetic picture now — so you and your doctor can make informed decisions before anything becomes urgent.
Learn more →You already took a DNA test. Here's what it couldn't tell you.
Most consumer DNA tests read less than 0.1% of your genome. We read all of it.
Learn more →Clinical-grade results. Chosen by individuals, trusted by doctors for their most complex cases.
Dante Genome Test helped specialists at a UK national acute hospital in the identification of Noonan Syndrome and a rare leukemia-associated genetic variant that had gone undetected. That result changed the medical care of the patient.
Accredited by & published in
Common questions about whole genome sequencing.
What is the difference between whole genome sequencing and a targeted genetic test?
Targeted genetic tests — including standard hereditary cancer panels — read a pre-defined list of known variants in a specific set of genes. They are designed to find what they already know to look for. Whole genome sequencing reads your entire genome: all 6 billion base pairs, every gene, every region between genes. A Mayo Clinic study published in JAMA Oncology found that standard testing guidelines missed more than half of patients with inherited cancer mutations. Genome Test does not have a fixed list.
What will I receive when my results are ready?
Your Dante Genome delivers 200+ physician-ready reports organized by clinical category — hereditary cancer, cardiac conditions, rare diseases, pharmacogenomics, carrier status, and more. Reports are delivered to your secure Genome Manager and are formatted for direct clinical use. Your genome data is permanently retained and re-analyzed automatically as science advances.
What happens if a clinically significant variant is found?
If a pathogenic or likely-pathogenic variant is identified, it will be clearly flagged in your physician-ready report with clinical context, published evidence, and recommended next steps. We recommend sharing any clinically significant finding with your physician or a genetic counselor, who can guide decisions about surveillance, risk reduction, or cascade testing for family members.
How is this different from a consumer DNA test like 23andMe or AncestryDNA?
Consumer DNA tests use genotyping chips that read less than 0.1% of your genome — a tiny pre-selected set of common variants. They are optimized for ancestry and population-level traits, not clinical genetic findings. The Dante Genome Test sequences 100% of your genome at 30X coverage, the same standard used in clinical diagnostic settings. The two tests are not comparable in scope, methodology, or clinical utility.
How long does it take to get results, and how are they delivered?
Your collection kit ships within 48 hours of ordering. Once your sample arrives at our CLIA-certified laboratory, sequencing and analysis takes 6–8 weeks. Results are delivered securely to your Genome Manager, where you can access your reports, share them with your physician, and receive automatic updates as new findings are validated against your genome.
We work with patient advocacy groups worldwide.
Dante Labs works with patient advocacy groups of any size — for Cerebral Cavernous Malformations and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
We can provide customized reports, group discounts, and packages tailored for your members. Please reach out using the form and we'll be in touch within two business days.
- Custom genomic reports for your members
- Group discounts and tailored packages
- Any country — including virtual groups
- Rare and common conditions covered
Message received.
We’ll be in touch within 2 business days. To follow up directly: hello@dantelabs.com
One test.
A lifetime of answers.
One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.
Ships within 48 hours · Results in 6–8 weeks
