Ehlers-Danlos Syndrome (EDS) refers to a group of 13 connective tissue disorders characterized by joint hypermobility, stretchy skin, and fragile tissues. These conditions result from genetic changes affecting the structure or processing of collagen and related proteins, which provide strength and support. Direct-to-consumer (DTC) genetic testing, such as 23andMe, is popular for exploring ancestry and health predispositions. This has led many to question if these services can provide information about complex conditions like EDS, requiring an understanding of the testing methodology’s limitations.
Understanding Direct-to-Consumer Genetic Testing Limitations
DTC genetic tests rely on a method different from clinical testing. These services typically utilize Single Nucleotide Polymorphism (SNP) microarray analysis, which scans the user’s DNA for hundreds of thousands of pre-selected locations.
The SNP-based approach checks only for specific, known variants; it does not read the entire gene sequence. This contrasts with full gene sequencing, which reads every DNA base pair to identify potential pathogenic variation. Since complex disorders like EDS involve thousands of changes across multiple genes, the SNP microarray checks only a small fraction.
DTC tests are regulated as screening tools for genetic predispositions, not as diagnostic tests. A clinical diagnosis requires a healthcare professional to use a physical examination, medical history, and comprehensive genetic testing. 23andMe reports are intended to inform, not to replace, consultation with a doctor or genetic specialist.
Ehlers-Danlos Syndrome Types and 23andMe’s Reporting
EDS is complex, comprising 13 subtypes. The most common type is hypermobile EDS (hEDS), which accounts for the majority of cases. hEDS is unique because it lacks a single, definitive genetic marker; its diagnosis relies entirely on clinical criteria. Since there is no established genetic test for hEDS, 23andMe cannot report on an individual’s risk for this prevalent subtype.
Other, less common types, such as Vascular EDS (vEDS) and Classical EDS (cEDS), are caused by identifiable genetic changes. vEDS is linked primarily to the COL3A1 gene, while cEDS is associated with variants in the COL5A1 and COL5A2 genes. 23andMe may screen for a limited set of variants in these genes. For instance, the test might check for a few pathogenic SNPs in COL3A1, relevant to vEDS, a type associated with arterial and organ fragility.
Even for these types, 23andMe checks only a tiny fraction of the known disease-causing variants. A positive result suggests an increased risk or carrier status for that particular variant. However, not finding the specific variants included in the test does not rule out having a different, untested pathogenic variant in the same gene or a variant associated with other rare EDS subtypes.
What a Positive or Negative Result Means
Interpreting a 23andMe result requires understanding the probabilistic nature of the findings. A “negative” result, meaning the test found none of the specific variants for vEDS or cEDS, does not eliminate the possibility of having EDS. This is particularly true for hEDS, which is not genetically tested, and because the test does not cover all pathogenic variants in the tested genes.
Conversely, a “positive” result, indicating a specific pathogenic variant in a gene like COL3A1 or COL5A1, means the individual has an increased genetic risk or is a carrier for that type of EDS. This finding is not equivalent to a clinical diagnosis. The concepts of penetrance and expressivity describe how a gene variant manifests.
Penetrance refers to the proportion of people with a specific genetic change who develop symptoms; high penetrance does not guarantee the condition will fully develop. Variable expressivity means that the type and severity of symptoms can differ widely, even among individuals with the same pathogenic variant. A positive DTC result signals potential risk warranting follow-up, but it does not confirm a diagnosis.
Consulting Specialists After Testing
Individuals who receive a positive DTC result or suspect they have EDS based on physical symptoms should seek clinical evaluation. The next step involves consulting a medical geneticist or a genetic counselor. These specialists are trained to interpret complex genetic findings within the context of a patient’s medical history and physical examination.
The clinical evaluation includes a detailed assessment of symptoms, such as joint hypermobility, skin characteristics, and family history, using established criteria for hEDS. If necessary, the specialist will order confirmatory diagnostic genetic testing, such as a multi-gene panel or whole exome sequencing. These clinical tests are designed to look for all known disease-causing variants in relevant genes and are performed in certified laboratories, ensuring accuracy for diagnosis.
Specialists may use the raw genetic data from the DTC test as preliminary information, but they will not rely on it for a formal diagnosis. The ultimate diagnosis of EDS is a clinical process that integrates genetic data with a thorough physical assessment. This comprehensive approach ensures the correct type of EDS is identified, leading to the most appropriate management and care plan.