Ehlers-Danlos Syndrome
Ehlers-Danlos Syndrome
Ehlers-Danlos Syndrome (EDS) is an inherited connective tissue disorder that is classified into six distinct primary types. EDS was first described around the turn of the century by Eduard Ehlers, a Danish physician, and Henri-Alexandre Danlos, a French physician. Before 1997 there were ten recognized types of EDS that were labeled with Roman numerals I through X. Once doctors had more experience with patients with EDS and as technology improved to study biochemical properties of tissue, it was recognized that some subtypes could be combined and reclassified. At a meeting in Villefranche-sur-Mer, France in 1997, experts in the field of connective tissue disorders such as Dr. Peter Beighton, Dr. Tsipouras and …show more content…
Dr. Wenstrup, met to redefine the subtypes. The revised nosology includes the following new descriptive names of the subtypes: hypermobility, classical, vascular, kyphoscoliosis, arthrochalasia, and dermatosparaxis. Even though each of the six distinctive types of EDS affects different aspects of a person’s body, they are all caused by the defect in the synthesis of collagen. More specifically the genes that are mutated most of the time are COL3A and COL5A.
The Hypermobility subtype, formerly Type III, is the most prevalent of all the subtypes with an estimated occurrence of 1 in 10,000 to 15,000 people. The genetic transmission is autosomal dominant and the subtype of EDS passed on to children always remains the same and does not change to another subtype form of the disease. The genes that are affected by this type are COL3A1 and TNXB. Since there is not a specific medical test for the hypermobility variety, diagnosis is based on the clinical history and the presence of specific symptoms. Joint instability, chronic musculoskeletal pains, joint hypermobility, frequent joint dislocation, pain, and osteoarthritis are symptoms of this hypermobility subtype and aid in the diagnosis. Some minor skin tearing may also occur and may impact surgical healing.
Many patients are not diagnosed until age thirty because by this time the patient’s clinical history is so extensive to where a pattern can be detected and a diagnosis reached.
By this stage many patients feel as though they have a body of an eighty year old despite being only thirty due to the level of pain and osteoarthritis. Frustration occurs as the pain level increases and recurrent subluxations or dislocations impact the patient’s life. Many patients have gone to numerous doctors or specialists only to be told that they are clumsy or that they are exaggerating the pain level. When a diagnosis is finally given, it is usually a relief to the patient to finally have an answer. Although there is no cure, physical therapy to strengthen muscles to make up for the lax ligaments can provide some strength to stabilize the joints to minimize injury. Orthotics can also provide support. Pain management is an important …show more content…
concern.
Most doctors when they hear EDS think of the classical subtype. Occurring in about 1 in 20,000 to 50,000 people and transmitted autosomal dominant, Classical variety affects type V collagen. Textbooks prior to 1997 feature many photos of the extreme skin elasticity of the classical or formally Type I and II variety. Generally, the skin on the neck and at the elbow is pulled to show the excessive stretching and elasticity. The collagen fibers of the classical type are fragile and spaced far apart leading to the ability to stretch the skin abnormally and resulting in easy bruising and tearing of the skin.
Poor wound healing provides a challenge to repair the frequent tearing of the skin from minor forces and makes patients with this subtype bad candidates for surgery. Stitches do not hold the tissue together well and creative approaches to wound repairs must be employed. The repair of the skin is with imperfect collagen, and the resulting new skin formed is thin and resembles cigar paper. Minor bumps result in discoloring of the skin and excessive scar formation. This scarring is especially prevalent at the joints where excessive force and exposure to bumps results in subcutaneous spheroids. All injuries must be treated with care to avoid excessive bleeding and permanent injury to the joint. The soft, velvety feel of the classical EDS skin is in contrast to the resulting disfiguring scarring that occurs once the skin is torn due to injury. Patients with Classical subtype mainly experience skin manifestations but they may also have joint problems as well.
The vascular variety of EDS (formerly Type IV) affects 1 in 100,000 to 250,000 people and is transmitted in an autosomal dominant pattern. The defect in the type III collagen results in fragile blood vessels and therefore the prognosis for people with the vascular variety is not very promising. The life expectancy is usually not past 40 or 50 years of age with some patients not living past age twenty. Usually the aorta dilates and ruptures or other life threatening complications such as intestinal rupture occur. Easy bruising is prevalent since the collagen that is fragile lines the blood vessels. Thin, translucent skin with the veins visible on the abdomen and chest are characteristic of the vascular variety. Generally patients also have a similar facial appearance with large eyes, small chin, sunken cheeks, thin nose and lips and lobeless ears. A skin biopsy called a skin punch can detect the vascular variety due to the presence of a COL3A1 defect. Geneticists can provide counseling regarding the genetic transmission of this lethal variety. Much research is being conducted on this subtype due to the severity of the symptoms and complications.
The kyphoscoliosis subtype (formerly Type VI) is manifested with scoliosis or curvature of the spine, fragile eyes (rupture of ocular globe), and severe muscle weakness. The enzyme lysyl hydroxylase (PLOD) is not produced and results in these symptoms. Fewer than 60 cases have been reported. Autosomal recessive is the mode of transmission. Loss of mobility early in life and blindness are severe complications resulting from this variety.
Another rare subtype is Arthrochalasia (formerly Types VII A & B)where the type I collagen is affected. Only about 30 cases have been described and are distinguished by mutation analysis of grown skin fibroblasts from a skin punch. Severe hypermobility of all joints and congenital hip dislocations are prominent characteristics. The transmission is autosomal dominant.
The final subtype is Dermatosparaxis (formerly type 7C) caused by a deficiency in procollagen I-N. Transmitted autosomal recessive, this subtype is diagnosed by the presence of redundant skin and a soft doughy texture to the skin. Large hernias are common and easy bruising occurs as well. Skin fragility is present but the scarring is not atrophic as in classical. This subtype is very rare with about 10 cases reported.
Former types V, VIII, IX and X have either been reclassified into other subtypes or occurred with just one family and have now been removed from the revised nosology of 1997.
A new seventh type is being discussed – Tenascin – X Deficient based on a recent discovery of tenascin contributing to EDS.
While the six subtypes of Ehlers- Danlos Syndrome affect different parts of the body, defective collagen is the common characteristic. Since collagen is present throughout the body with each collagen form present in different amounts in each body system, the effects of Ehlers- Danlos Syndrome are diverse. Ehlers-Danlos Syndrome is still widely undiagnosed as many doctors have not kept current with the revised nosology and think of it as a rare disorder. The prevalence of EDS is thought to be higher due to the lack of appropriate diagnosis.
Medical students are taught the following saying: “If you hear hoof beats, think horses.” In other words, based on the symptoms you see think of the most likely or common cause or diagnosis. Don’t think of the rare causes because they are not likely to happen. However, in the case of Ehlers-Danlos Syndrome, a relatively rare genetic disorder, the symptoms are not due to clumsiness or just a common joint problem. A favorite twist on the saying for patients with Ehlers-Danlos is, “If you hear hoof beats, think zebras.” While no cure has been developed for EDS, there is hope for a brighter tomorrow. Research is directed at genetic
engineering so that better collagen can be generated for future generations.
Bibliography
http://www.arthritis.org/conditions-treatments/disease-center/ehlers-danlos-syndrome- eds/. Arthritis Foundation, October 8, 2013
http://www.ednf.org/. Ehlers-Danlos National Foundation, October 8, 2013
http://www.ehlersdanlosnetwork.org/. Ehlers-Danlos Network Cares, October 8, 2013
http://en.wikipedia.org/wiki/Ehlers%E2%80%93Danlos_syndrome. Wikipedia, October 5, 2013
http://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome. National Institute for Health, Genetics Home Reference, October 6, 2013
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002439/. National Institute for Health, October 3, 2013.
Ehlers-Danlos Syndrome (EDS) is an inherited connective tissue disorder that is classified into six distinct primary types. EDS was first described around the turn of the century by Eduard Ehlers, a Danish physician, and Henri-Alexandre Danlos, a French physician. Before 1997 there were ten recognized types of EDS that were labeled with Roman numerals I through X. Once doctors had more experience with patients with EDS and as technology improved to study biochemical properties of tissue, it was recognized that some subtypes could be combined and reclassified. At a meeting in Villefranche-sur-Mer, France in 1997, experts in the field of connective tissue disorders such as Dr. Peter Beighton, Dr. Tsipouras and …show more content…
Dr. Wenstrup, met to redefine the subtypes. The revised nosology includes the following new descriptive names of the subtypes: hypermobility, classical, vascular, kyphoscoliosis, arthrochalasia, and dermatosparaxis. Even though each of the six distinctive types of EDS affects different aspects of a person’s body, they are all caused by the defect in the synthesis of collagen. More specifically the genes that are mutated most of the time are COL3A and COL5A.
The Hypermobility subtype, formerly Type III, is the most prevalent of all the subtypes with an estimated occurrence of 1 in 10,000 to 15,000 people. The genetic transmission is autosomal dominant and the subtype of EDS passed on to children always remains the same and does not change to another subtype form of the disease. The genes that are affected by this type are COL3A1 and TNXB. Since there is not a specific medical test for the hypermobility variety, diagnosis is based on the clinical history and the presence of specific symptoms. Joint instability, chronic musculoskeletal pains, joint hypermobility, frequent joint dislocation, pain, and osteoarthritis are symptoms of this hypermobility subtype and aid in the diagnosis. Some minor skin tearing may also occur and may impact surgical healing.
Many patients are not diagnosed until age thirty because by this time the patient’s clinical history is so extensive to where a pattern can be detected and a diagnosis reached.
By this stage many patients feel as though they have a body of an eighty year old despite being only thirty due to the level of pain and osteoarthritis. Frustration occurs as the pain level increases and recurrent subluxations or dislocations impact the patient’s life. Many patients have gone to numerous doctors or specialists only to be told that they are clumsy or that they are exaggerating the pain level. When a diagnosis is finally given, it is usually a relief to the patient to finally have an answer. Although there is no cure, physical therapy to strengthen muscles to make up for the lax ligaments can provide some strength to stabilize the joints to minimize injury. Orthotics can also provide support. Pain management is an important …show more content…
concern.
Most doctors when they hear EDS think of the classical subtype. Occurring in about 1 in 20,000 to 50,000 people and transmitted autosomal dominant, Classical variety affects type V collagen. Textbooks prior to 1997 feature many photos of the extreme skin elasticity of the classical or formally Type I and II variety. Generally, the skin on the neck and at the elbow is pulled to show the excessive stretching and elasticity. The collagen fibers of the classical type are fragile and spaced far apart leading to the ability to stretch the skin abnormally and resulting in easy bruising and tearing of the skin.
Poor wound healing provides a challenge to repair the frequent tearing of the skin from minor forces and makes patients with this subtype bad candidates for surgery. Stitches do not hold the tissue together well and creative approaches to wound repairs must be employed. The repair of the skin is with imperfect collagen, and the resulting new skin formed is thin and resembles cigar paper. Minor bumps result in discoloring of the skin and excessive scar formation. This scarring is especially prevalent at the joints where excessive force and exposure to bumps results in subcutaneous spheroids. All injuries must be treated with care to avoid excessive bleeding and permanent injury to the joint. The soft, velvety feel of the classical EDS skin is in contrast to the resulting disfiguring scarring that occurs once the skin is torn due to injury. Patients with Classical subtype mainly experience skin manifestations but they may also have joint problems as well.
The vascular variety of EDS (formerly Type IV) affects 1 in 100,000 to 250,000 people and is transmitted in an autosomal dominant pattern. The defect in the type III collagen results in fragile blood vessels and therefore the prognosis for people with the vascular variety is not very promising. The life expectancy is usually not past 40 or 50 years of age with some patients not living past age twenty. Usually the aorta dilates and ruptures or other life threatening complications such as intestinal rupture occur. Easy bruising is prevalent since the collagen that is fragile lines the blood vessels. Thin, translucent skin with the veins visible on the abdomen and chest are characteristic of the vascular variety. Generally patients also have a similar facial appearance with large eyes, small chin, sunken cheeks, thin nose and lips and lobeless ears. A skin biopsy called a skin punch can detect the vascular variety due to the presence of a COL3A1 defect. Geneticists can provide counseling regarding the genetic transmission of this lethal variety. Much research is being conducted on this subtype due to the severity of the symptoms and complications.
The kyphoscoliosis subtype (formerly Type VI) is manifested with scoliosis or curvature of the spine, fragile eyes (rupture of ocular globe), and severe muscle weakness. The enzyme lysyl hydroxylase (PLOD) is not produced and results in these symptoms. Fewer than 60 cases have been reported. Autosomal recessive is the mode of transmission. Loss of mobility early in life and blindness are severe complications resulting from this variety.
Another rare subtype is Arthrochalasia (formerly Types VII A & B)where the type I collagen is affected. Only about 30 cases have been described and are distinguished by mutation analysis of grown skin fibroblasts from a skin punch. Severe hypermobility of all joints and congenital hip dislocations are prominent characteristics. The transmission is autosomal dominant.
The final subtype is Dermatosparaxis (formerly type 7C) caused by a deficiency in procollagen I-N. Transmitted autosomal recessive, this subtype is diagnosed by the presence of redundant skin and a soft doughy texture to the skin. Large hernias are common and easy bruising occurs as well. Skin fragility is present but the scarring is not atrophic as in classical. This subtype is very rare with about 10 cases reported.
Former types V, VIII, IX and X have either been reclassified into other subtypes or occurred with just one family and have now been removed from the revised nosology of 1997.
A new seventh type is being discussed – Tenascin – X Deficient based on a recent discovery of tenascin contributing to EDS.
While the six subtypes of Ehlers- Danlos Syndrome affect different parts of the body, defective collagen is the common characteristic. Since collagen is present throughout the body with each collagen form present in different amounts in each body system, the effects of Ehlers- Danlos Syndrome are diverse. Ehlers-Danlos Syndrome is still widely undiagnosed as many doctors have not kept current with the revised nosology and think of it as a rare disorder. The prevalence of EDS is thought to be higher due to the lack of appropriate diagnosis.
Medical students are taught the following saying: “If you hear hoof beats, think horses.” In other words, based on the symptoms you see think of the most likely or common cause or diagnosis. Don’t think of the rare causes because they are not likely to happen. However, in the case of Ehlers-Danlos Syndrome, a relatively rare genetic disorder, the symptoms are not due to clumsiness or just a common joint problem. A favorite twist on the saying for patients with Ehlers-Danlos is, “If you hear hoof beats, think zebras.” While no cure has been developed for EDS, there is hope for a brighter tomorrow. Research is directed at genetic
engineering so that better collagen can be generated for future generations.
Bibliography
http://www.arthritis.org/conditions-treatments/disease-center/ehlers-danlos-syndrome- eds/. Arthritis Foundation, October 8, 2013
http://www.ednf.org/. Ehlers-Danlos National Foundation, October 8, 2013
http://www.ehlersdanlosnetwork.org/. Ehlers-Danlos Network Cares, October 8, 2013
http://en.wikipedia.org/wiki/Ehlers%E2%80%93Danlos_syndrome. Wikipedia, October 5, 2013
http://ghr.nlm.nih.gov/condition/ehlers-danlos-syndrome. National Institute for Health, Genetics Home Reference, October 6, 2013
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002439/. National Institute for Health, October 3, 2013.