Hereditary Spastic Paraplegia — progressive lower limb spasticity caused by 80+ different genes, where molecular diagnosis distinguishes treatable mimics from true HSP and predicts whether the disease will remain pure or develop complex features.
Whole genome sequencing evaluates all 80+ HSP genes simultaneously — SPG4 (SPAST), SPG3A (ATL1), SPG7 (paraplegin), and the full genetic landscape — replacing the sequential single-gene testing that delays diagnosis by years.
Hereditary Spastic Paraplegia
Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by progressive length-dependent degeneration of the corticospinal tract, producing lower limb spasticity and weakness. Over 80 genetic loci (SPG1 through SPG80+) and their corresponding genes have been identified, with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. The most common form is SPG4 (SPAST gene, encoding spastin), accounting for approximately 40% of autosomal dominant HSP cases. Combined prevalence of all HSP forms is approximately 2-10 per 100,000.
HSP is classified as 'pure' (uncomplicated — spasticity and weakness limited to the lower limbs, with or without urinary urgency and mild sensory loss) or 'complex' (complicated — spasticity plus additional neurological features such as ataxia, peripheral neuropathy, cognitive impairment, thin corpus callosum, epilepsy, or optic atrophy). The distinction between pure and complex HSP has major prognostic implications: pure HSP typically allows independent ambulation for decades, while complex HSP may include progressive cognitive decline, wheelchair dependence, and shortened life expectancy.
HSP is frequently misdiagnosed. The differential includes primary progressive multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), vitamin B12 deficiency, copper deficiency, spinal cord compression, dopa-responsive dystonia, and structural myelopathy. Many HSP patients undergo years of investigation — MRI brain and spine, lumbar puncture, evoked potentials, NCS/EMG — without a definitive diagnosis. Molecular confirmation through comprehensive genetic testing ends the diagnostic odyssey, provides accurate prognosis (pure vs. complex trajectory), enables genetic counseling for family members, and excludes treatable mimics.
SPG7 (paraplegin) is a common cause of recessive HSP that frequently presents with cerebellar ataxia — it is increasingly recognized as one of the most common genetic ataxias and should be considered in any adult with progressive spastic ataxia.
With 80+ causative genes, sequential single-gene testing is impractical. WGS evaluates the complete HSP genetic landscape in one test — ending diagnostic odysseys that average 5-10 years for rare HSP subtypes.
Ending the diagnostic odyssey — average HSP diagnostic delay is 5-10 years, during which treatable mimics may be missed
HSP patients typically undergo years of neurological investigation before receiving a molecular diagnosis. During this period, treatable conditions that mimic HSP — dopa-responsive dystonia (GCH1), B12/copper deficiency, structural myelopathy, primary progressive MS — may be under-investigated because the clinical picture is attributed to 'possible HSP.' Whole genome sequencing either confirms HSP with a specific gene identification (providing prognosis and reproductive counseling) or excludes HSP, redirecting investigation toward potentially treatable conditions.
SPG4 (SPAST) exon deletions account for 20% of SPG4 cases — invisible to standard sequencing
Approximately 20% of SPG4 pathogenic alleles are multi-exon deletions or duplications in SPAST — structural variants that are not detectable by standard exon sequencing or Sanger sequencing. A patient with autosomal dominant pure HSP who tests negative on SPAST sequencing may actually carry a SPAST deletion. Whole genome sequencing detects both sequence variants and copy number variants from the same data, identifying the complete spectrum of SPAST pathogenic alleles in a single test without requiring separate MLPA analysis.
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.
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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 Hereditary Spastic Paraplegia 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
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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
