From the Guidelines
Diagnosing Ehlers-Danlos syndrome (EDS) typically involves genetic testing, which is the most definitive laboratory method for identifying most types of this connective tissue disorder, with a focus on identifying mutations in specific genes such as COL3A1 for vascular EDS 1. To diagnose EDS, the following lab tests may be used:
- Genetic testing to identify mutations in specific genes such as COL5A1, COL5A2, COL3A1, and PLOD1
- Skin biopsy for collagen analysis to reveal abnormal collagen structure or production
- Biochemical tests, such as measuring lysyl hydroxylase enzyme activity in kyphoscoliotic EDS or analyzing urinary pyridinoline crosslinks
- Echocardiograms and other cardiovascular imaging to assess for heart valve abnormalities or vascular complications, particularly in vascular EDS These tests are typically ordered after a thorough clinical assessment that suggests EDS based on symptoms like joint hypermobility, skin hyperextensibility, and tissue fragility, as laboratory testing alone is insufficient for diagnosis and must be interpreted alongside clinical findings 1. The most recent and highest quality study, published in 2024, emphasizes the importance of genetic testing in diagnosing vascular EDS, highlighting that identification of a causal COL3A1 variant is a requirement for diagnosis 1. In clinical practice, it is essential to prioritize genetic testing for COL3A1 mutations in patients suspected of having vascular EDS, given the high risk of life-threatening vascular complications associated with this condition 1.
From the Research
Lab Tests for Diagnosing Ehlers-Danlos Syndrome
To diagnose Ehlers-Danlos syndrome (EDS), several lab tests can be utilized, focusing on the genetic and molecular aspects of the condition. The following are key points regarding lab work for EDS diagnosis:
- Genetic Testing: This is a crucial tool for diagnosing EDS, as it can identify mutations in the genes associated with the syndrome, such as COL5A1 and COL5A2 for classical EDS 2, 3, 4.
- COL5A1 and COL5A2 Gene Analysis: Mutations in these genes are commonly found in patients with classical EDS. Techniques such as sequencing, SSCP (Single-Strand Conformation Polymorphism), and CSGE (Conformation Sensitive Gel Electrophoresis) can be used to detect these mutations 2, 4.
- Type V Collagen Defects: Analyzing fibroblast cultures for type V collagen defects can also aid in diagnosis, although this method may not be as sensitive as genetic testing 4.
- Next-Generation Sequencing: This approach can be particularly useful for identifying novel mutations or when the diagnosis is unclear, as it allows for the simultaneous analysis of multiple genes associated with vascular diseases, including EDS 5.
- Mutation Detection Rate: The detection rate of mutations in COL5A1 and COL5A2 genes can vary, with studies suggesting that approximately 50% to 93% of patients with classical EDS may harbor mutations in these genes 2, 3, 4.
Key Genes and Mutations
- COL5A1 and COL5A2: These genes encode the α1 and α2 chains of type V collagen, respectively. Mutations in these genes are primarily associated with classical EDS 2, 3, 4.
- COL1A1: Although less commonly associated with classical EDS, mutations in COL1A1 can lead to a phenotype resembling classical EDS with arterial complications 6, 2.
- COL3A1: This gene is associated with vascular EDS, characterized by fragile vasculature and a high risk of catastrophic vascular events 5.
Diagnostic Challenges
- Phenotypic Variability: There is significant inter- and intra-familial phenotypic variability among EDS patients, making diagnosis based solely on clinical criteria challenging 2, 3.
- Genotype-Phenotype Correlations: The lack of clear genotype-phenotype correlations in EDS means that genetic findings must be interpreted in the context of clinical presentation and family history 2, 3, 4.