# How Many of Us Are There? ### The PRRT2 count, the invisible thousands, and the official number that's almost certainly wrong by an order of magnitude *An Alliance Perspective ยท May 29, 2026* {% hint style="success" %} **๐Ÿงญ PRRT2.org Perspective** *PRRT2.org's own perspective โ€” our synthesis and lived experience, offered alongside the established science, not as established medical fact.* {% endhint %} Every official source describes PRRT2 as rare. Every patient who finds their way to a community like ours finds otherwise. How rare is the PRRT2 mutation actually? The official answer is some version of *1 in 150,000.* That figure appears in OMIM, GeneReviews, NORD, and every peer-reviewed PRRT2 review on the shelf. It is, almost certainly, **wrong by an order of magnitude** โ€” and not because anyone falsified it. Because the math the field built it from doesn't describe what the field uses it to describe. Once you do the math properly โ€” gene-centered, not phenotype-centered โ€” the picture changes. So does the case for treating this condition like it actually matters. ## The number you'll be told Open any reference page on PRRT2 and you'll see some version of: *"PKD has an estimated prevalence of 1 in 150,000 individuals."* That figure traces back to Chen and colleagues in 2011 and was formalized by Ebrahimi-Fakhari and colleagues in 2015. Across a world population of 8.1 billion, the math gives you about **54,000 people worldwide with PKD.** Now read it again. *"**PKD** has a prevalence of 1 in 150,000."* Not PRRT2. PKD. The condition, not the gene. This is the first, and biggest, substitution in how PRRT2 epidemiology gets communicated. The field built its prevalence figure for the most-studied PRRT2 condition and then let that figure stand in, in the public mind, for the prevalence of the gene itself. They are not the same number. They were never the same number. Treating them as the same is how the count of an entire gene quietly becomes the count of one of its conditions. ## The math when you actually center the gene To estimate the actual population of people carrying PRRT2 pathogenic variants, you have to walk through the chain. The field rarely walks anyone through it. **Step 1: PKD overall โ€” roughly 54,000 worldwide** (the canonical 1 in 150,000 figure). **Step 2: PKD with a PRRT2 cause.** Not every PKD case is PRRT2-driven. Other genes (notably TMEM151A) and sporadic causes exist. PRRT2 dominates *familial* PKD and accounts for a smaller fraction of *sporadic* PKD; combined, it sits around 60โ€“70% of PKD cases. That puts **PRRT2-PKD at roughly 32,000โ€“38,000 worldwide.** **Step 3: Scale to the whole gene.** This is the step the field never asks readers to take. In the 2015 *Brain* meta-analysis by Ebrahimi-Fakhari and colleagues โ€” the most rigorous catalogue of published PRRT2 cases assembled โ€” **PKD accounted for only 38.7% of patients.** The rest presented with benign familial infantile epilepsy (41.7%), the combined ICCA syndrome (14.3%), and other phenotypes (5.3%). PKD is the most-studied PRRT2 condition. It is not the most common one. **BFIE actually exceeds it.** If PKD is roughly 39% of PRRT2 phenotypes, the symptomatic PRRT2 population is about 2.5 times the PRRT2-PKD count: **somewhere in the range of 80,000 to 100,000 people** with a recognized PRRT2 condition worldwide. **Step 4: Add asymptomatic carriers.** PRRT2 has incomplete penetrance โ€” many carriers never develop noticeable symptoms, never see a clinician, never get tested. Penetrance estimates vary across studies, but the commonly cited range is roughly 60โ€“80%. Apply that to the symptomatic population: total carriers in the **100,000 to 150,000 range worldwide.** **Step 5: Account for the wider spectrum the count doesn't include.** This step is harder to put a number on, but it matters. As described in [Exploring the Wider Spectrum](https://www.prrt2.org/exploring-the-wider-spectrum), there are real patients living with PRRT2 whose presentations โ€” generalized dystonia, dysphonia, exertional patterns, atypical seizures, mixed paroxysmal phenotypes, persistent symptoms into adulthood โ€” don't fit the textbook categories that the 2015 review used. They are absent from the published count entirely. The number we just calculated is *still conservative*, because it only includes the phenotypes the field has agreed to name. So when people ask *how many of us are there*, the honest answer is some version of: **100,000 to 150,000 worldwide, very possibly more, with about three thousand of us actually documented in the medical literature.** A gap of **thirty-five to fifty times.** Or wider. A reasonable reader, presented with these numbers, has every right to ask the obvious question. ## Is this hidden on purpose? No. And we are not going to insult anyone's intelligence by claiming otherwise. There is no conspiracy. There is no committee suppressing the real PRRT2 count. There is something worse, in a way: **the under-count doesn't require a conspiracy. The system produces it automatically.** **Ascertainment bias.** The published count only ever included patients who reached researchers and got reported. People who never present to a clinician โ€” because their symptoms are mild, or were dismissed, or were misdiagnosed as something else, or because they were never offered testing โ€” never enter the literature. The published number is a measure of who got reached. It is not a measure of who has the gene. **The "benign" labels.** For years the field referred to BFIS as "benign familial infantile epilepsy" and to PKD as a "benign" paroxysmal disorder. That language did real damage. It told clinicians, patients, and funders that PRRT2 was a thing children outgrow. Only in 2025 and 2026 โ€” in papers we reference in [Current Literature](https://www.prrt2.org/research/current-literature) โ€” has the literature begun to acknowledge what patients have been saying for years: PRRT2-related conditions are *"not invariably benign."* That correction is two decades late. Adults whose conditions never resolved, who carry persistent and disabling symptoms into mid-life, have been waving at a field whose own vocabulary instructed it not to look. **The pediatric tilt.** PRRT2 research has been overwhelmingly concentrated on pediatric phenotypes โ€” infantile seizures, childhood-onset PKD โ€” because those are where the gene presents in the cleanest, most diagnosable form. The adult tail, the long arc, the persistent symptoms beyond age twenty, the atypical presentations that don't fit the textbook silhouette: those are systematically under-studied. The literature is a map of where children with PRRT2 reach pediatric neurologists. It is not, in any meaningful sense, a map of where adults with PRRT2 live. **Siloed diagnosis.** PRRT2 conditions get split across specialties. Seizures go to pediatric neurology. Movement episodes go to a movement-disorder clinic. Headaches go to a headache specialist. Dystonia and dysphonia each get their own appointment. Without a clinician zooming out to look for the underlying genetic cause, each piece is named in isolation โ€” and the patient never gets a PRRT2 diagnosis, never enters the count. **The geographic gap.** PRRT2 research has been concentrated in certain regions and certain academic centers. The first molecularly confirmed African PKD case wasn't published until 2020. Whole continents are essentially unrepresented in the published record โ€” not because the gene is absent there, but because the testing infrastructure isn't. The literature is a map of where research happened, not a map of where carriers live. None of these is deliberate suppression. All of them combine into the same effect: a published count wrong by an order of magnitude, and reference pages that quietly substitute one condition's prevalence for an entire gene's. If you want to call something out for being hidden, don't call out individuals. Call out the structure. It's doing the hiding all by itself, and the field is, at long last, beginning to admit as much. ## Why this matters โ€” concretely This isn't an abstract accounting problem. The undercount has real-world consequences for real people. **Research funding and pharmaceutical development follow the numbers.** *"About 3,000 documented cases, very rare"* is a fundamentally different proposition to a funder than *"100,000+ likely carriers, severely under-recognized."* For a condition with no targeted therapy whatsoever (see [Beyond the Blunt Instruments](/perspectives/articles/beyond-blunt-instruments.md)) โ€” where every drug currently used is borrowed from another condition โ€” the count is part of why nothing has been built for us specifically. **The smaller the number looks, the smaller the case for investment looks.** And the case for investment is, in the end, the case for the future of treatment. **Clinician familiarity follows the numbers.** When the literature reports a couple of thousand cases, every clinician implicitly assumes they're unlikely to ever see one โ€” so PRRT2 doesn't enter the differential. When the real population is fifty times larger, many of them already *have* seen patients with this gene and missed it. Under-counting reinforces under-recognition, which reinforces under-counting. **Patients searching for themselves are guided by the numbers.** Someone with unexplained paroxysmal episodes, or generalized dystonia with no clear cause, or atypical seizures who has been told *"we don't know what this is,"* reads "PRRT2: prevalence 1 in 150,000" and concludes they probably don't have it. If the real figure for the *gene* is closer to 1 in 50,000 โ€” and reaches across phenotypes most people have never heard of โ€” far more would pursue testing and find their answer. **The consequences compound.** Every adult living with PRRT2 today who could be diagnosed but isn't, every clinician who could recognize this gene but doesn't, every funder who could prioritize this research but won't โ€” is being shaped, partly, by a number. That number is wrong. We don't believe it's wrong by malice. We do believe it's wrong in a way the field is collectively responsible for, has been slow to admit, and is only now beginning to correct in print. That correction is happening too quietly, and decades too late. **One of the jobs of this site is to say it louder, sooner, and to more people.** ## What the Alliance is doing about it We can't unilaterally recount the world's PRRT2 patients. We can refuse to accept the undercount as the truth, and we can build the conditions for a more honest count to emerge. * **Documenting the wider spectrum.** Adults and atypical presentations have to stop being missed โ€” [Exploring the Wider Spectrum](https://www.prrt2.org/exploring-the-wider-spectrum) exists for exactly that purpose. * **Pushing the language.** The field is finally beginning to say *"not invariably benign."* We will keep saying it louder, sooner, and more directly than the textbooks do. * **Supporting registries and natural-history studies.** These are the realistic near-term path to a more accurate count. (See [Clinical Trials](https://www.prrt2.org/research/clinical-trials) on why being counted matters.) * **Reaching the undiagnosed** through plain-language education someone can find by searching their symptoms โ€” not just by being referred to a movement-disorder specialist they may never see. The invisible thousands aren't a poetic phrase. They are real people โ€” carrying the same gene, often the same symptoms, often the same decades of confusion โ€” who simply haven't been counted yet. Some of them are reading this page right now and don't yet know the gene has a name. **The work, as much as anything, is making sure they find their way to it.** ## Sources * [OMIM โ€” Entry 614386 (PRRT2)](https://omim.org/entry/614386) โ€” Johns Hopkins University. * [GeneReviews โ€” PRRT2-Related Disorder (NBK475803)](https://www.ncbi.nlm.nih.gov/books/NBK475803/) โ€” University of Washington / NCBI. * [NORD โ€” PRRT2-Associated Paroxysmal Movement Disorders](https://rarediseases.org/rare-diseases/prrt2-associated-paroxysmal-movement-disorders/) โ€” National Organization for Rare Disorders. * Ebrahimi-Fakhari D, Saffari A, Westenberger A, Klein C. *The evolving spectrum of PRRT2-associated paroxysmal diseases.* **Brain** 138(12):3476โ€“3495, 2015. For the complete reference set, see [Official Resources](https://www.prrt2.org/resources/official-resources). ## Continue reading * [Current Literature](https://www.prrt2.org/research/current-literature) โ€” including the recent shift in how the field labels PRRT2's severity * [Exploring the Wider Spectrum](https://www.prrt2.org/exploring-the-wider-spectrum) โ€” the cases the count doesn't reflect * [Beyond the Blunt Instruments](/perspectives/articles/beyond-blunt-instruments.md) โ€” why the count shapes the treatment landscape *** *If you carry a PRRT2 variant โ€” or you suspect you do โ€” your story is part of how the real number gets built. Share it with the community through* [*Links & Support*](https://www.prrt2.org/resources/links-and-support)*, or add it to* [*Patient Stories*](https://www.prrt2.org/living-with-prrt2/patient-stories)*. The invisible thousands stop being invisible one voice at a time.* --- # Agent Instructions: Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. Perform an HTTP GET request on the current page URL with the `ask` query parameter: ``` GET https://www.prrt2.org/perspectives/articles/how-many-of-us.md?ask= ``` The question should be specific, self-contained, and written in natural language. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.