The current diagnostic criteria for Ehlers-Danlos syndrome (EDS) might not effectively identify certain patients with borderline symptoms of the disease, making genetic testing crucial in these cases, a study reports.
In 2017, EDS experts published the criteria used to diagnose the disease, known as the 2017 EDS nosology. But there is concern in the medical community that some EDS cases might go undiagnosed because the current criteria overlook certain aspects of the disease.
Genetic abnormalities underlying the disease may help to identify these cases. For example, more than 90 percent of patients with classical EDS have a genetic abnormality in genes coding for certain collagen types (COL5A1 and COL5A2), which are proteins that serve as essential structural components in the body.
The study, “A classical Ehlers-Danlos syndrome family with incomplete presentation diagnosed by molecular testing,” was published in the European Journal of Medical Genetics. It identified two patients who did not meet the current diagnostic criteria but who had genetic abnormalities underlying EDS.
The first patient was a 23-year-old woman who showed signs of skin abnormalities similar to those observed in EDS, including skin hyperextensibility. But she had not been formally diagnosed with the disease because she did not meet some of the mandatory criteria for classification, according to the 2017 EDS nosology.
The second patient was her 51-year-old mother, who showed similar symptoms but also did not meet the 2017 EDS nosology criteria.
This led researchers to conduct molecular analyses to test both patients for genetic abnormalities in the COL5A1 and COL5A2 genes.
A genetic change in the COL5A1 gene was detected in both patients (the c.4068G > A COL5A1 variant), which the team believed resulted in defective collagen protein. No molecular studies regarding the functional consequences of this genetic change were carried out in the current study, as the patients did not agree to participate in further research.
Based on genetic analysis, both patients were diagnosed with classical EDS.
“This work demonstrates that rare EDS patients with a borderline clinical presentation may not meet the 2017 EDS criteria and would not be diagnosed without genetic testing, underlying that the clinical variability is wider than depicted by the current nosology and the relevance of molecular analysis,” researchers wrote.
“In doubtful patients, molecular analysis should be performed to possibly conclude the diagnostic process, as it happened in this case,” they added.