Rare disease diagnosis, one finding at a time.
Rare diseases are individually uncommon but collectively common, and their symptoms overlap. Getting from a patient's findings to the right diagnosis often takes years. This guide explains how a phenotype-driven differential diagnosis is built, and where GENA's free tools and GENA 3.0 help.
Why rare diseases are hard to diagnose
There are thousands of rare diseases. Orphanet alone describes several thousand, and our ICD-10 Map covers 8,980 of them. Most clinicians will see any one of them only a handful of times in a career, if at all.
Three things make the search hard:
- Symptoms overlap. Developmental delay, seizures or joint pain point to hundreds of conditions at once.
- Findings are scattered. They sit in free-text notes written by different specialists over months or years, in different words.
- Absent findings matter too. "No rash" or "normal hearing" rules diagnoses out, but is rarely recorded in a structured way.
The result is the diagnostic odyssey: years of referrals and tests before a family gets an answer.
How a phenotype-driven differential diagnosis works
Most rare disease decision support, including GENA 3.0, follows the same four steps.
Capture the findings
Collect what the patient has and does not have, from notes, exams and history. Present and absent findings both count.
Code them in a shared language
Map each finding to the Human Phenotype Ontology (HPO), so “joint pain” and “arthralgia” mean the same thing to software. PhenoLens does this step for free.
Compare against disease profiles
Score each candidate disease by how well its known features match the patient's, and how much its missing features count against it.
Rank, explain and narrow
Produce a ranked differential with a rationale for each disease, then suggest the next finding or test that best separates the leading candidates. This is what GENA 3.0 does.
Where GENA's free tools fit
Each free GENA Labs tool handles one step of a rare disease workup, in your browser and without an account:
- PhenoLens turns a clinical note into HPO codes and marks each finding present or absent, so the phenotype is ready for analysis.
- Gene Standing shows whether expert groups agree that a gene really causes a disease, which matters when a genetic test reports a variant.
- ICD-10 Map shows which ICD-10-CM code a rare disease is filed under once it is diagnosed, and what that code loses.
Where GENA 3.0 takes over
GENA 3.0 is clinical decision support for the whole case. It takes the patient's findings and returns a ranked differential diagnosis across 30,408 diseases, each with a plain-language rationale, an evidence graph linking findings to diseases, disease summaries with citations, and a suggested next workup. An AI consultant answers questions about the case. It runs as a web app, or inside your EHR through a SMART on FHIR API.
GENA 3.0 supports clinical reasoning; it does not replace it. The clinician makes the diagnosis.
Common questions
What is a rare disease?
In the United States, a rare disease is one that affects fewer than 200,000 people. In the European Union, the threshold is fewer than 1 in 2,000 people. Most rare diseases are genetic, and many first appear in childhood.
What is a differential diagnosis?
A differential diagnosis is the list of conditions that could explain a patient's findings, ordered by how likely each one is. Clinicians narrow it with further history, examination and tests.
What are HPO codes and why do they matter?
The Human Phenotype Ontology (HPO) is a standard vocabulary of clinical findings, such as HP:0001945 for fever. Coding findings in HPO lets software compare a patient against thousands of disease profiles consistently. PhenoLens converts a clinical note into HPO codes for free.
Can software diagnose a rare disease?
No. Software such as GENA 3.0 supports diagnosis by ranking candidate diseases and explaining why. A clinician reviews the evidence, orders confirmatory tests and makes the diagnosis.
How do I get access to GENA 3.0?
Use the Open GENA 3.0 button on this page to request access. The free GENA Labs tools need no account.
Turn findings into a ranked differential with GENA 3.0.
GENA 3.0 turns a patient’s symptoms into a ranked differential diagnosis, each backed by a plain-language rationale. Use it as a web app, or connect your EHR through a FHIR-compliant API.
Open GENA 3.0- Ranked differential across 30,408 diseases
- Evidence graph linking findings to diseases
- Disease summaries with citations
- AI consultant for the case
- Suggested next workup
- EHR-ready (SMART on FHIR)