Genetic Disorder: Ehlers-Danlos Syndrome
by Misti Blu Day McDermott
Ehlers-Danlos Syndrome is an inherited heterogeneous group of thirteen subtypes in which abnormal collagen synthesis affects connective tissue: skin, bones, ligaments, blood vessels, organs and tissue (NLM). Collagen is a major structural component of the body, making up approximately 25% of the total protein content. There are around 28 types of collagen, though collagen type I is the most prolific type. Type I collagen is found in vascular ligature, skin, tendons, organs, and bones. Mutations, such as COL1A1, affecting type I collagen are rare and may result in tearing and rupture of major arteries, blood vessels, and organs. This particular mutation results in the replacement of the amino acid arginine with cysteine, altering the pro-a1(I) chain. Normal collagen consists of strong and stable cross-links of long, thin fibrils. There are multiple components that make up the procollagen molecule chains. Instability of collagen can be due to nutritional deficiencies or the gene instructions in which a genetic mutation affects a critical segment of the assembly process of mature collagen production (Genetic Home Reference).
Danish dermatologist Edvard Ehlers recognized the condition in 1901. In 1908, a French physician named Henri-Alexandre Danlos suggested the features of the syndrome. However, in the recent years, molecular diagnostic strategies have since advanced. With collaborative research, education, awareness, and advocacy, research shows that this once considered rare genetic disorder is perhaps greatly under-diagnosed (Ehlers-Danlos Society). Weak and structurally abnormal collagen may result in flexible and loose joints, fatigue, sleep disturbances, chronic pain, postural orthostatic tachycardia syndrome, gastrointestinal disorders, poor wound healing, fragile blood vessels, ruptured or prolapsed organs, dysautonomia and many other various health conditions. Symptoms vary based on which of the thirteen subtypes the patient is diagnoses with. Different genes are associated with different subtypes; therefore, symptoms can range from mild to life threatening.
There is currently no molecular genetic cause linked to hEDS, the most common type. This type requires the patient to meet specific criteria for diagnosis in order to assist in clinical management and the potential research efforts to find the associated gene. Benign or asymptomatic hypermobility with no linked gene basis is now being diagnosed as Hypermobility Syndrome. The HEDGE study launch collaborated with Ehlers-Danlos Society will collect enough data to gain more knowledge of this rarely diagnosed disorder.
The inheritance patterns vary based on each subtype. Autosomal dominant inheritance only requires one copy of an altered gene to produce the disorder, whereas autosomal recessive requires two copies of an abnormal gene. For other subtypes, the disorder can be inherited from one affected parent and some even develop new gene mutations that occur with no family history. The gene mutation for COL1A2 can be found on chromosome seven, altering the collagen found in most connective tissue. This particular gene is associated with cardiac-valvular EDS, atypical Marfan Syndrome and Osteogenesis Imperfecta.
For formal diagnosis, a referral to a geneticist is a start. There is test called the Beighton Scale, which has helped assess hypermobility since 1998. Medical history is also important for diagnosis. There is a list of diagnosis criteria for each subtype that require a patient to meet a certain amount of history and symptoms. Vascular EDS can be potentially fatal, which makes proper diagnosis and subtype classification important.
Ehlers-Danlos Syndrome is not curable but symptoms may be managed with a team of specialists. It is a systemic disorder, meaning that multiple systems may be affected. Many patients see a range of specialists such as pulmonology, electrophysiology, cardiology, gastroenterology, neurology, pain management, etc. Specialists involved depend on the patient’s specific symptomatic issues that are a result of the connective tissue disorder.
The current statistics for the more common subtypes are 1 in 2,500 to 1 in 5,000. Some of the rarer types only have a handful of documented cases. Since recent clinical studies show that EDS is more common and not so much rare as it is rarely diagnosed, this makes awareness, education and advocacy so important, in order to better understand and diagnose this disorder. Professor and UK Rheumatologist Rodney Grahame stated that, “no other disease in the history of modern medicine has been neglected in such a way as Ehlers-Danlos Syndrome.”
The Ehlers-Danlos Society. What Are The Ehlers-Danlos Syndromes? Retrieved from https://www.ehlers-danlos.com/what-is-eds/
National Library of Medicine. (April 2019). Genetics Home Reference: Ehlers-Danlos Syndrome. Retrieved from https://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome
National Library of Medicine. (December 2019). Genetic Home Reference: COL1A1Gene. Retrieved from https://ghr.nlm.nih.gov/gene/COL1A1#conditions