DEFENITION AND TYPES OF EHLER’S DANLOS

I am particularly interested in Ehler’s-Danlos Syndrome because, as I have mentioned before, my beautiful niece was born with and suffers daily with it and complications directly related to this syndrome.  I have found the best information from the Ehler’s-Danlos Foundation.  I am going to put the definition and the types here.

WHAT IS EHLER’S DANLOS?

The Ehlers-Danlos syndromes are inherited in the genes that are passed from parents to offspring. They are categorized according to the form of genetic transmission into different types with many features differing between patients in any given type. The fragile skin and loose joints and tissue fragility is often a result of abnormal genes that produce abnormal proteins that confer an inherited frailty of collagen (the normal protein “glue” of our tissues). In 2001, researchers discovered a new form of Ehlers-Danlos syndrome that is caused by an inherited abnormality in a protein other than collagen that also normally plays a role in binding together the cells of our tissues (including the skin, tendons, muscle, and blood vessels). Abnormalities in this protein, called tenascin, also lead to a form of Ehlers-Danlos syndrome. Researchers suspect that tenascin could play a role in regulating the normal distribution of collagen in the connective tissues of the body.

CLASSICAL TYPE

The Classical Type of EDS is characterized by highly elastic, soft, and doughy skin; unusual scarring; and loose joints. This type of Ehlers-Danlos Syndrome combines the types formerly called I and II. Ehlers-Danlos Syndrome, Classical Type is a subtype of Ehlers-Danlos Syndrome. People with the Classical Type have smooth, velvety skin that is stretchy, fragile, and easily bruised. Wounds often split open with little bleeding, heal slowly, and leave characteristic thin, wide scars (“cigarette paper” scars). People with this condition also have loose joints with an unusually large range of movement (hypermobility). As a result, joints are prone to dislocation, sprains, and the early-onset arthritis. Non-cancerous fibrous growths on pressure points (such as elbows) and fatty growths on the forearms and shins are also common. Other manifestations include weak muscle tone in infants due to hypermobility, which can make them seem “floppy” and delay the development of motor skills such as sitting, standing, and walking. As many as half of the people with Classical Type Ehlers-Danlos Syndrome have a condition called mitral valve prolapse, which affects blood flow between the chambers of the heart. The Classical Type is one of the most common forms of Ehlers-Danlos Syndrome. This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In the rare cases caused by TNXB mutations, the condition has shown an autosomal recessive pattern of inheritance, which means two copies of the gene must be altered for a person to be affected by the disorder. Clinical Diagnosis The clinical diagnosis of EDS, Classic Type is established by family history and clinical examination. Diagnostic criteria was developed by a medical advisory group in a conference (sponsored by the Ehlers-Danlos Foundation [USA] and the Ehlers-Danlos Support Group [UK]) at Villefranche in 1997 [Beighton et al 1998] The combination of the first three major diagnostic criteria should have a high specificity for EDS, Classical Type. The presence of one or more minor criteria contributes to the diagnosis of the Classical Type of EDS but is not sufficient to establish the diagnosis. Major Diagnostic Criteria for the Classical Type of EDS Skin hyperextensibility should be tested at a neutral site (one not subjected to mechanical forces or scarring), such as the volar surface of the forearm. It is measured by pulling up the skin until resistance is felt. In young children, hyperextensibility of the skin is difficult to assess because of abundant subcutaneous fat. Widened atrophic scars (a manifestation of tissue fragility) Joint hypermobility depends on age, gender, and family and ethnic backgrounds. Joint hypermobility in Classical Type EDS is general, affecting both large and small joints. It is usually noted when a child starts to walk. It should be assessed using the Beighton scale [Beighton 1988], the most widely accepted grading system for the objective semi-quantification of joint hypermobility Positive Family History Minor Diagnostic Criteria for the Classical Type of EDS Smooth, velvety skin Molluscoid pseudotumors: fleshy, heaped-up lesions associated with scars over pressure points such as the elbows and knees Subcutaneous spheroids: small, cyst-like, hard shot-like nodules, freely movable in the subcutis over the bony prominences of the legs and arms. They occur in about one-third of affected individuals, are numerous, and feel like hard grains of rice. X-ray reveals an outer calcified layer with a translucent core. The spheroids represent subcutaneous fat globules that have lost their blood supply, becoming fibrosed and calcified. Complications of joint hypermobility (sprains, dislocations,subluxations, pes planus) Muscle hypotonia, delayed gross motor development Easy bruising Manifestations of tissue extensibility and fragility (hiatal hernia, anal prolapse in childhood, cervical insufficiency) Surgical complications (postoperative hernias) Disclaimer The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about Ehlers-Danlos syndrome, should consult with a qualified healthcare professional.

HYPERMOBILITY TYPE

The Hypermobility Type of EDS is characterized by loose joints and chronic joint pain. This form of Ehlers-Danlos Syndrome was formerly called type III. Ehlers-Danlos Syndrome, Hypermobility Type is a subtype of Ehlers-Danlos Syndrome. The most common sign of this condition is an unusually large range of joint movement, called hypermobility. Both large and small joints are unstable, and certain joints (such as the shoulder, knee, and jaw) tend to dislocate frequently. Chronic joint and limb pain often begins early in life. People with this condition may have skin that is soft, velvety, or stretchy; however, skin symptoms vary among people. Many affected people also have a condition called mitral valve prolapse, which affects blood flow between the chambers of the heart. The Hypermobility Type is the most common  form of Ehlers-Danlos Syndrome. The Hypermobility Type of Ehlers-Danlos Syndrome is most often inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In these cases, family members in each generation are usually affected, but the features of the condition may vary. In some families, a recessive pattern of inheritance may be possible. This inheritance pattern means that two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene Clinical Diagnosis Clinical diagnostic criteria and a revised nomenclature for all forms of Ehlers-Danlos Syndrome (EDS) were proposed by [Beighton et al 1998]. EDS, Hypermobility Type is distinguished from EDS, Classical Type chiefly by milder and fewer skin and soft tissue manifestations. The diagnosis of EDS, Hypermobility Type is based entirely on clinical evaluation and family history. The criteria listed below reflect those proposed by [Beighton et al 1998] as modified by the author’s experience. Major Diagnostic Criteria for the Hypermobility Type or EDS Joint hypermobility, which usually is confirmed by a score of five or more on the nine-point Beighton scale [Beighton et al 1973], including: -One point for passive dorsiflexion of each fifth finger >90º -One point for passive apposition of each thumb to the flexor surface of the forearm -One point for hyperextension of each elbow >10º -One point for hyperextension of each knee >10º -One point for ability to place the palms on the floor with the knees fully extended Soft or velvety skin with normal or slightly increased extensibility Skin hyperextensibility is assessed at a site lacking excess or loose skin and without evidence of prior trauma by gently pulling until resistance is met. Extensor surfaces of joints should not be used because of the presence of excess skin. An ideal location is the volar surface of the forearm, where the upper limit of normal is approximately 1-1.5 cm. Absence of skin or soft tissue fragility, which is suggestive of other types of EDS. Examples include: -Spontaneous or easily induced skin cuts or tears -Spontaneous or easily induced tears or ruptures of tendons, ligaments, vessels, or other internal organs -Atrophic (“cigarette paper”) scars (although mildly atrophic scars are sometimes seen in the hypermobility type, especially in areas subject to physical stress, such as extensor surfaces and the abdominal wall) Molluscoid pseudotumors Surgical complications, such as incisional hernia, wound dehiscence, or sutures tearing through tissues and failing to hold Minor Diagnostic Criteria for the Hypermobility Type of EDS Family history of similar features without significant skin or soft tissue fragility in a pattern consistent with autosomal dominant inheritance Recurrent joint dislocations or subluxations Chronic joint or limb pain Easy bruising Functional bowel disorders (functional gastritis, irritable bowel syndrome) Neurally mediated hypotension or postural orthostatic tachycardia High, narrow palate Dental crowding The sensitivity and specificity of examination for joint hypermobility is dependent in part on the individual’s age, gender, and medical history. Young children (approximately five years of age or younger) tend to be very flexible and are therefore difficult to assess. Women are, on average, more flexible than men Older individuals tend to lose flexibility, and post-surgical or arthritic joints often have reduced range of motion. A history of former joint laxity or clinical demonstration of substantial laxity in multiple joints is sometimes accepted in lieu of a positive Beighton score in such cases, if the family history and other minor criteria are strongly suggestive There is disagreement as to whether the “benign familial articular hypermobility syndrome” is identical to EDS, hypermobility type or represents a unique condition [Grahame 1999]. The distinction is subtle and relates to degree of joint complications and presence or absence of skin manifestations. However, first-degree relatives of probands with EDS, Hypermobility Type often have relatively asymptomatic joint laxity and mild or absent skin manifestations. Therefore, the benign hypermobility syndrome is included as EDS, Hypermobility Type for this review. Disclaimer The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about Ehlers-Danlos Syndrome, should consult with a qualified healthcare professional.

THE VASCULAR TYPE

The Vascular Type of EDS is characterized by possible arterial or organ rupture as a result of spontaneous rupture of vessels or organs due to the result of even minor trauma. The Vascular Type of EDS is the most serious form of Ehlers-Danlos Syndrome. If a patient presents with signs of chest, neck, abdominal pain (etc.) it should be considered a TRAUMA SITUATION. Patient complaints should be immediately investigated using an MRA, MRI or CT-Scan rather than x-rays since expedient diagnosis and treatment is so critical to the survival of a Vascular EDS patient. Please keep in mind that the Vascular Type of EDS is extremely hard to diagnose. Since so many patients are misdiagnosed with another form of EDS extreme caution should be taken with all forms of this disorder. The Vascular Type is a subtype of Ehlers-Danlos Syndrome. People with the disorder have thin, fragile skin that bruises easily. Veins are visible beneath the skin, particularly on the chest and abdomen, and hands and feet may have an aged appearance. Unlike people with other forms of Ehlers-Danlos Syndrome, people with the Vascular Type have skin that is soft but not overly stretchy. Facial features are often distinctive, including protruding eyes, a thin nose and lips, sunken cheeks, and a small chin. Other signs of the disorder include an unusually large range of movement (hypermobility) of hand and foot joints, tearing of tendons and muscles, painfully swollen veins in the legs, lung collapse, and slow wound healing following injury or surgery. Infants with the condition may be born with hip dislocations and a foot disorder called clubfoot, which causes the foot to turn inward and downward. Unpredictable ruptures of arteries and organs are the most serious complications of the Vascular Type of Ehlers-Danlos Syndrome. A torn artery can cause internal bleeding, stroke, or shock, and is the most common cause of death in patients with this disorder. Rupture of the intestine is seen in 25 to 30 percent of affected individuals and tearing of the uterus (womb) during pregnancy affects 2 to 3 percent of women. Although serious problems are rare in childhood, more than 80 percent of patients experience severe complications by the age of 40. The vascular type is a rare form of Ehlers-Danlos Syndrome. Mutations in the COL3A1 gene cause the Vascular Type of Ehlers-Danlos Syndrome. The protein made by the COL3A1 gene is used to assemble larger molecules called type III collagens. Collagens provide structure and strength to connective tissue throughout the body. Type III collagen is mostly found in skin, blood vessels, and internal organs. If the structure or production of type III collagen is altered by a mutation in the COL3A1 gene, collagen fibrils cannot be assembled properly in these tissues, and the signs and symptoms of the Vascular Type of Ehlers-Danlos Syndrome result. This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. About half of all cases are inherited from a parent who has the condition. The other half of cases occur in people whose families have no history of the disorder; these sporadic cases are caused by new mutations in one copy of the COL3A1 gene. Clinical Diagnosis Diagnostic criteria and standardized nomenclature for the Ehlers-Danlos Syndromes were suggested by a medical advisory group in a conference sponsored by the Ehlers-Danlos Foundation (USA) and the Ehlers-Danlos Support Group (UK) at Villefranche in 1997 [Beighton et al 1998]. Criteria are modified here to reflect the authors’ experience. The combination of any two of the major diagnostic criteria should have a high specificity for the Vascular Type of EDS. Biochemical testing is strongly recommended to confirm the diagnosis. The presence of one or more minor criteria supports the diagnosis of the vascular type of EDS but is not sufficient to establish the diagnosis. Major Diagnostic Criteria for the Vascular Type of EDS Arterial rupture Intestinal rupture Uterine rupture during pregnancy Family history of the vascular type of EDS Minor Diagnostic Criteria for the Vascular Type of EDS Thin, translucent skin (especially noticeable on the chest/abdomen) Easy bruising (spontaneous or with minimal trauma) Characteristic facial appearance (thin lips and philtrum, small chin, thin nose, large eyes) Acrogeria (an aged appearance to the extremities, particularly the hands) Hypermobility of small joints Tendon/muscle rupture Early-onset varicose veins Arteriovenous carotid-cavernous sinus fistula Pneumothorax/pneumohemothorax Chronic joint subluxations/dislocations Congenital dislocation of the hips Talipes equinovarus (clubfoot) Gingival recession RITTERS RULES FOR AORTIC DISEASES – I found this information at the Ritter Foundation for Aortic Health Ritter Rules Ritter Rules are life-saving reminders to recognize, treat and prevent thoracic aortic dissection, a deadly tear in the large artery that carries blood away from the heart. Named for actor John Ritter, who died of a thoracic aortic dissection, Ritter Rules combine knowledge with action. Know the urgency, symptoms, who is most at-risk and which imaging tests are required to diagnose this medical emergency. URGENCY: Thoracic aortic dissection is a medical emergency. The death rate increases 1% every hour the diagnosis and surgical repair are delayed. PAIN: Severe pain is the #1 symptom. Seek immediate emergency medical care for a sudden onset of severe pain in the chest, stomach, back or neck. The pain is likely to be sharp, tearing, ripping, moving . Some people report feeling that something is very wrong. MISDIAGNOSIS: Aortic dissection can mimic heart attack. Heart attacks are far more common than aortic dissection, but if a heart attack or other diagnosis is not clearly and quickly established, then aortic dissection should be quickly considered and ruled out. This is especially important if a patient has a family history of thoracic aortic aneurysm/dissection or features of a genetic syndrome that predisposes the patient to an aortic aneurysm or dissection. IMAGING: Get the right scan to rule out aortic dissection. Only three types of imaging studies can identify aortic aneurysms and dissections: CT, MRI and transesophageal echocardiogram. Note: A chest x-ray or EKG cannot rule out aortic dissection. RISK FACTOR: Aortic dissections are often preceded by an enlargement of the first part of the aorta where it comes out of the heart, called an aortic aneurysm. If you have an aneurysm, you are at increased risk for an aortic dissection. RISK FACTOR: A personal or family history of thoracic disease puts you at risk. If you or a family member are living with an aneurysm or if you have a family member who has had an aortic dissection, you are at an increased risk for thoracic aortic aneurysm and/or dissection. You and other family members should be evaluated to determine if a predisposition for aortic aneurysm and dissection is running in your family. RISK FACTOR: Certain genetic syndromes that affect connective tissue put you at risk. These genetic syndromes greatly increase your risk for thoracic aortic disease and a potentially fatal aortic dissection: Marfan syndrome, Loeys-Dietz syndrome, vascular Ehlers-Danlos syndrome, and Turner syndrome. RISK FACTOR: Bicuspid aortic valve disease puts you at risk. If you have a bicuspid aortic valve (two leaflets instead of the typical three), or have had a bicuspid aortic valve replaced, you need to be monitored for thoracic aortic disease. TRIGGERS: Lifestyle and trauma can trigger aortic aneurysm and/or dissection. It is possible to trigger an aortic dissection through injury to the chest, extreme straining associated with body building, illicit drug abuse, poorly controlled high blood pressure or by discontinuing necessary blood pressure medications. Rarely, pregnancy can trigger an aortic dissection. However, women with aortic aneurysms and connective tissue disorders who are pregnant are at higher risk of aortic dissection during late pregnancy and delivery and should be carefully monitored by a cardiovascular specialist. PREVENTION: Medical management is essential to preventing aortic dissection. If you have thoracic aortic disease, medical management that includes optimal blood pressure control, aortic imaging and genetic counseling is strongly recommended. Talk with your physician.

KYPHSCOLIOSIS TYPE

The Kyphoscoliosis Type of EDS is characterized by generalized joint laxity and severe muscle hypotonia (weak muscle tone) at birth. The muscular hypotonia can be very pronounced and leads to delayed gross motor development. Individuals with the Kyphoscoliosis Type of EDS present with a progressive form of scoliosis at birth. The phenotype is most often severe, frequently resulting in the loss of ambulation in the second or third decade. Scleral fragility may lead to rupture of the ocular globe after minor trauma. Tissue fragility including atrophic scars and easy bruising. Spontaneous arterial rupture can occur. Other Findings May Include Marfanoid Habitus (Marfan like features) Micro Cornea (abnormally small cornea) Radiologically Considerable Osteopenia (diminished amount of bone tissue) The Kyphoscoliosis Type of EDS is the result of a deficiency of lysylhydroxylase (PLOD), which is a collagen-modifying enzyme. This type of EDS is inherited in an autosomal recessive manner. The Kyphoscoliosis Type of EDS can be diagnosed through a urine test.

ARTHROCHALASIA TYPE

The Arthrochalasia Type of EDS is characterized by congenital hip dislocation which is present in all biochemically proven individuals with this type of EDS. Severe generalized joint hypermobility with recurrent subluxations are seen in individuals with this type of EDS. Other manifestations of this type may include Skin hyperextensibility with easy bruising Tissue fragility including atrophic scars Muscle Hypotonia Kyphoscoliosis Radiologically Mild Osteopenia. The Arthrochalasia Type od EDS is caused by mutations leading to deficient processing of the amino-terminal end of proa1(I) [type A] or proa2(I)[type B] chains of collagen type I. It is inherited in an autosomal dominant manner. A skin biopsy can also diagnose this type of EDS.

DERMATOSPAREXIS TYPE

The Dermatosparaxis Type of EDS is characterized by severe skin fragility and substantial bruising. Wound healing is not impaired and the scars are not atrophic. The skin texture is soft and doughy. Sagging, redundant skin is evident. The redundancy of facial skin results in an appearance resembling cutis laxa. Large hernias(umbilical, inguinal) may also be seen. The number of patients reported with this type of EDS is small. The Dermatosparaxis Type of EDS is caused by a deficiency of procollagenI N-terminal peptidase. It is inherited in a autosomal recessive manner. A skin biopsy can diagnose this type of EDS.

TENASCIN-X DEFICIENT

The Tenascin-X Deficient Type of EDS is characterized by joint hypermobility, hyperelastic skin, and fragile tissue. Lacking multiple shrinking (atrophied) scars in the skin that is often seen in the Classic Type of Ehlers-Danlos Syndrome. Inherited as an autosomal recessive genetic trait (not seen in family members or only in one generation of members of the same family).

Emergency Room

Vascular Emergency Information Vascular Type EDS is considered the most serious form of EDS due to the possibility of arterial or organ rupture. If a patient presents with signs of chest, abdominal pain (etc.) it should be considered a TRAUMA SITUATION. Patient complaints should be immediately investigated using MRA, MRI, or CT-Scan testing — not x-rays.

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