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Hypermobility Type

Joint hypermobility is the dominant clinical manifestation. Generalized joint hypermobility that affects large (elbows, knees) and small (fingers, toes) joints is evident in the Hypermobility Type. Recurring joint subluxations and dislocations are common occurrences. Certain joints, such as the shoulder, patella and temporomandibular joint dislocate frequently. The skin involvement (smooth velvety skin with or without hyperextensibility) as well as bruising tendencies in the Hypermobility Type are present but quite variable in severity.

Chronic pain is a well-established and cardinal manifestation of Hypermobility EDS and it is common for pain to be out of proportion to physical and radiological findings. The origin of the pain is not clearly understood, but some of the likely causes include muscle spasm (tender points are sometimes present) and degenerative arthritis; neuropathic pain is also common.

To date, there is no distinctive biochemical collagen finding identified for the majority of Hypermobility cases. The Hypermobility Type of EDS is inherited in an autosomal dominant manner.

Hypermobility Frequently Asked Questions

Ehlers-Danlos syndrome (EDS) is an inherited connective tissue disorder with varying manifestations that have been classified into six major types: Classical (type I & II), Hypermobility (type III), Vascular or VEDS (type IV), Kyphoscoliosis (type VI), Arthrochalasia (types VII-A & B), and Dermatosparaxis (type VII-C). EDS is caused by a defect in the formation of collagen, specifically mutations in the COL5A and COL3A genes, which can cause hypermobility in joints. EDS gets its name after two physicians who identified it at the turn of the 20th century, Edvard Ehlers (Denmark) and Henri-Alexandre Danlos (France).

The types of EDS are not gradations in severity, but represent distinct disorders that "run true" in a family. The different types are classified according to their manifestations of signs and symptoms. The underlying features of all forms of EDS is a genetic alteration at the molecular level which causes abnormalities and (weakened) defective connective tissue within the collagen itself.

Collagen is a protein that acts like "glue", which holds the body together, and makes the connective tissue strong and provides elasticity. Each type of EDS has a different collagen abnormality, but all share, in varying degrees certain manifestations. This faulty collagen causes structural changes to the skin, ligaments, tendons, bone, fascia and eyes. Some types of EDS are characterized by weaknesses in the walls of the hollow organs of the gastrointestinal tract, in the esophagus, the cardiovascular system, uterus, bladder, blood vessels and the arteries. Diagnosing a specific type of EDS may not be easy, however, because the manifestations often overlap. The fundamental understanding of this complex disorder and its varied manifestations is essential to prevent major life-threatening complications.

There are varying degrees of severity with EDS that can range from having loose joints which may dislocate easily with few other complications, to connective tissues which are so fragile — the skin splits and gaps with minimal injury, to extreme dislocations/laxity of joints which don't stay in place, to major blood vessels that may rupture and produce internal bleeding or the bowel may rupture. EDS may include:

Skin

Some patients may have fragile soft velvet-like skin, stretchy skin (hyperextensibility), very doughy skin, and/or some have thin skin which shows the underlying blood vessels. The condition of fragile skin that tears easily and that is susceptible to easy bruising can be mild to severe. Other characteristics of EDS patients’ skin includes "cigarette paper" scars, slow healing, severe scarring, slow and poor wound healing, and development of molluscoid pseudotumors (fleshy lesions associated with scars over pressure areas).

Joints

Joint hypermobility loose/unstable joints which are prone to frequent dislocations and/or subluxations; joint pain; hyperextensible joints (they move beyond the joint's normal range); shoulders, spine, elbows, wrists, knees, ankles, and laxity in the hands and fingers; and early onset of osteoarthritis.

Hollow Organs

Aortic root dilatation, aortic aneurysms, aortic rupture, bowel rupture and uterine fragility have all been noted in patients with EDS. These are more commonly found in the Vascular (VEDS) Type, though.

Miscellaneous/Less Common

Chronic, early onset, debilitating musculoskeletal pain (usually associated with the Hypermobility Type); Scoliosis at birth and scleral fragility (associated with the Kyphoscoliosis Type); poor muscle tone (associated with the Arthrochalasia Type); mitral valve prolapse; and gum disease.

EDS is genetic. There are two different inheritance patterns of EDS. They are known as autosomal dominant and autosomal recessive. It is important to remember that regardless of the pattern of inheritance, we have no control over which genes we pass on to our children. Depending on the EDS type, there are significant percentages of affected individuals who have a de novo disease-causing mutation. What is autosomal dominant? What is autosomal recessive?

Mosaicism denotes the presence of two populations of cells in one patient, where one of the two is usually affected by a genetic disorder. Although most forms of trisomy are due to problems in meiosis and affect all cells of the zygote, there are cases where the trisomy only occurs in a selection of the cells. Generally this leads to a milder phenotype than in non-mosaic patients with the same disorder. Post-zygote event: a mutational event or abnormally in chromosome replication/segregation that occurs after fertilization of the ovum by the sperm, often leading to mosaicism. Germline mosaicism denotes two or more genetic or cytogenetic cell lines confined to the precursor (germline) cells of the egg or sperm, formally called gonadal mosaicism. Somatic mosaicism denotes two or more genetic or cytogenetic cell lines within the cell of the body (may or may not include the germline cells). Isolated: an abnormality that occurs in the absence of other systemic involvement.

Resources: Milewicz, D. M., Witz, A. M., Smith, A. C. M., Manchester, D. K., Waldstein, G., Byers, P. H.: Parental somatic and germ-line mosaicism for a multiexon deletion with unusual endpoints in a type III collagen (COL3A1) allele produces Ehlers-Danlos syndrome type IV in the heterozygous offspring. Am. J. Hum. Genet. 53: 62–70, 1993.

Genetic counselors are medical professionals who are trained in medical genetics and counseling. They deal with the occurrence or risk of occurrence of a genetic disorder in a family. They most often work in conjunction with a medical geneticist (physician). They provide an accurate presentation of the facts to a patient who has been diagnosed or who is a known carrier of a genetic disorder. Most people find the genetic aspect of the disorder confusing.

A genetic counselor will help you sift through the facts to gain a better understanding of your inheritance pattern. They provide nondirective counseling to those who are considering starting a family to facilitate making an informed decision. They may act as a resource for educational information about a disorder, as a psychosocial counselor for families in crisis, as a link to support services/support groups and as a coordinator for patient care.

Laboratory confirmation of certain types of Ehlers–Danlos syndrome is possible. These include the Classical, Vascular (VEDS), Kyphoscoliosis, Arthrochalasia and Dermatosparaxis Types. If these types of EDS are suspected based on the clinical findings, the geneticist or your physician may recommend or offer laboratory confirmation.

The genetic counselor may be the liaison between the patient and the genetic laboratory. In this role the counselor may be responsible for explaining the technical information to patients and other health care providers. The genetic counselor will most often be the person to explain how the testing will be done, the costs involved and the estimated length of time for test completion.

The tests involved are usually performed at highly specialized laboratories. Because they are often not the center where a person is being evaluated, the genetic counselor may also be responsible for gathering all pertinent medical information such as medical records, family history and consent forms. When lab results become available, the genetic counselor and the geneticist will meet with the patient or family to discuss the results and implications of the new findings.

Currently, there is no cure for Ehlers-Danlos syndrome, so medical intervention is limited to symptomatic therapy, prophylactic measures and counseling. Some individuals with EDS have little disability, whereas other people can be severely handicapped. Often, people are plagued with chronic pain. EDS must be treated on an individualized basis and discussed with your primary caretakers. EDS is generally not a disorder which causes someone to "stick out like a sore thumb." Often individuals describe a frustration at having to restrict various activities and trying to explain why to others. Many individuals learn to cope with their disorder and have the potential to pursue countless careers and lead a full and active life. However, some patients are troubled by hypotonia (low muscle tone), joint instability and chronic joint pain. These symptoms should be recognized and discussed, and lifestyles and professional choices should be adapted accordingly.

EDS is a lifelong condition, some individuals may face social obstacles related to their disorder on a daily basis. Some report living with fears of significant and painful skin ruptures, becoming pregnant (especially those with Vascular EDS), their condition worsening, unemployment, physical and mental burdens and social stigmatization's in general.

Resources: Java O. Solis, MD: A Health Advantage, "Ehlers-Danlos Syndrome"

For each individual with EDS, the clinical story is unique. There isn't a single answer as to why an individual might have features of more than one type of EDS. The first step that they could take to sort this out is to visit a medical geneticist. It is possible that they might benefit from laboratory testing to confirm the molecular or biochemical basis of the form of EDS that they have. Sometimes, but not always, the testing helps to clarify the clinical confusion. It may be, however, that they have features of more than one type of EDS because they have a connective tissue disorder that hasn't yet been "described," meaning that the underlying protein abnormality or gene mutation is unknown. Future research studies will be necessary to answer the question. Answered by Melanie Pepin MS, CGC

All people with EDS should have a routine physical examination that includes an assessment of blood pressure and auscultation of the heart (listening to the heart). At this point, unless there is a rhythm disturbance (irregular heart beat) or a murmur, there is no consensus in the literature what people should have further examined. This is an emerging field. Studies are now being done to assess if MRA, for example, would be helpful in imaging and following people with Vascular EDS (type IV). Some people with Classical EDS (type I) appear to have a risk for aortic enlargement, but who and what proportion are not known so further study is needed. Answered by Peter Byers, MD

A routine noninvasive cardiovascular evaluation should be performed in all EDS patients in order to exclude valvular heart disease and dilation of the aortic root or other vessels, including the coronary arteries. [DiMario et al., 1988 Jpn Heart J 29 (4): 491–6]

Due to the recent study [R. Wenstrup et al., 2002], looking at the incidence of aortic root dilation in non-Vascular Type EDS (22% in Hypermobility, 33% in Classical) Dr. Lavallee recommends ultrasound imaging the heart and aorta every two years for most patients and yearly ultrasounds for those with known dilatation, Vascular Type, hypertension, involved in a highly dynamic sport or diabetic. Answered by Mark Lavallee, MD, FACSM

Certainly Hypermobility EDS (type III). Probably for some people with Classical EDS (type I and II). Back pain with scoliosis in Kyphoscoliosis EDS (type VI). Joint pain and early degenerative arthritis are part of EDS type VII. Answered by Peter Byers, MD

"The present study indicates that chronic, frequently debilitating pain of early onset and diverse distribution is a constant feature in most individuals affected with different types of EDS." Functional impacts of chronic pain impact sleep, sexual functioning, social relations, physical activity, school and/or job functioning. Although individuals with Vascular EDS seem to have a substantially smaller number of painful locations as compared to individuals with Classical and Hypermobility Types. Because EDS is relatively rare, systematic study of pain in this population or of its relief has not been performed. EDS should be considered in the differential diagnosis of chronic musculoskeletal pain." [Sacheti A. et al.: Chronic Pain is a Manifestation of the Ehlers-Danlos Syndrome. J Pain Symp Mana, Vol. 14, (2): 88–93].

“Chronic pain is a well-established and cardinal manifestation of EDS and it is common for pain to be out of proportion to physical and radiological findings. The etiology of EDS pain is not clearly understood, but some of the likely causes include muscle spasm (tender points are sometimes present) and degenerative arthritis; neuropathic pain is also common.” [EDNF's Pain Management Medical Resource Guide available elsewhere on this site.]

"Chronic pain, distinct from that associated with acute dislocations or advanced osteoarthritis, is a serious complication of the condition and can be both physically and psychologically disabling." [Howard P Levy, MD, PhD. Ehlers-Danlos Syndrome, Hypermobility Type. GeneReviews,  http://www.ncbi.nlm.nih.gov/books/NBK1279/.]

"The results of this study show that 1) chronic pain in EDS is highly prevalent and associated with regular use of analgesics; 2) pain is more prevalent and more severe in the hypermobility type than in the classic type; 3) pain severity is correlated with hypermobility, dislocations and previous surgery; 4) pain is correlated with low nocturnal sleep quality; and 5) pain contributes to functional impairment in daily life, independently of the level of fatigue. From this large cohort of EDS patients, we conclude that pain is common and severe in EDS. Pain is related to hypermobility, dislocations, and previous surgery and associated with moderate to severe impairment in daily functioning… Our findings suggest that pain is a very common and severe symptom in this group of EDS patients. It is related to dislocations, sleep disturbances and moderate-to-severe impairment in daily functioning. Therefore, treatment of pain should be a prominent aspect of clinical management of EDS." [Nicol C. Voermans, MD, Hans Knoop, PhD, Gijs Bleijenberg, PhD, and Baziel G. van Engelen, MD, PhD. “Pain in Ehlers-Danlos Syndrome Is Common, Severe, and Associated with Functional Impairment.” J Pain Symptom Manage. 2010 Sep;40(3):370–8.]

Back and neck pain are a common report among patients with all types of EDS. Pain often does not correlate with the presence or absence of spinal deformity. Hypermobility Type was the most debilitating form with respect to musculoskeletal function. Surgical procedures to the musculoskeletal system,(shoulder, elbow, feet, knee, or ankle) to alleviate pain, instability, poor range of motion or a combination of these are commonly performed. [Weinberg et al., Joint Surgery in EDS Patients: results of a survey].

Search for better ways to find mutations in Classical EDS (type I and II). Search for the common genes in Hypermobile EDS (type III). Search for genes in EDS type VIII (Classical Type with periodontitis) is ongoing. Answered by Peter Byers, MD

Dysautonomia means dysfunction of the autonomic nervous system. The autonomic nervous system is the master regulator of all unconscious organ function throughout the body. It is involved in the control of heart rate, blood pressure, temperature, respiration, digestion and other vital functions. Dysfunction of the autonomic nervous system can produce the apparent malfunction of the organs it regulates. For this reason, dysautonomia patients often exhibit numerous, seemingly unrelated maladies.

Orthostatic intolerance is present when patients experience symptoms such as lightheadedness, palpitations and tremulousness during standing. Many patients also note other symptoms with upright posture: visual changes, discomfort in the head or neck, throbbing of the head, poor concentration, tiredness, weakness and occasionally fainting. Patients can be severely impaired by these symptoms and signs, such as a bluish-red suffusion of skin in the lower extremities on standing, which are relieved by lying down.

Postural Orthostatic Tachycardia Syndrome (POTS)

Often more simply referred to as postural tachycardia syndrome, or POTS, this disorder is characterized by the body's inability to make the necessary adjustments to counteract gravity when standing up. The defining symptom of POTS is an excessive heart rate increment upon standing. However, as you will discover, there are a multitude of other symptoms that often accompany this syndrome. POTS can be a difficult disorder to detect and understand.

More information on POTS.

Neurocardiogenic Syncope (NCS)

Sometimes referred to as neurally mediated syncope or vasovagal syncope, this disorder is characterized by an episodic fall in blood pressure and/or heart rate that results in fainting [Robertson, 2002].

Pure Autonomic Failure (PAF)

Pure Autonomic Failure is a degenerative disease of the peripheral nervous system characterized by a marked fall in blood pressure upon standing (orthostatic hypotension). The orthostatic hypotension leads to symptoms associated with cerebral hypoperfusion, such as dizziness, fainting, visual disturbances and neck pain [Mathias, Mallipeddi & Bleasdale-Barr, 1999]. Other symptoms such as chest pain, fatigue and sexual dysfunction may also occur. Symptoms are worse when standing and are sometimes relieved by sitting or lying flat.

References:

Mathias, C. J., Mallipeddi, R. and Bleasdale-Barr, K. (1999). Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple system atrophy. Journal of Neurology, 246, (10), 893–898.

MEDLINEPlus Heath Information. (2003). Multiple System Atrophy. Retrieved September 8, 2003 from: http://www.nlm.nih.gov/medlineplus/ency/article/000757.htm

Extraarticular manifestations of the joint hypermobility syndrome may include the peripheral nervous system. The autonomic nervous system-related symptoms of the patients have a pathophysiological basis which suggests that dysautonomia is extraarticular manifestation in the joint hypermobility syndrome. 

Resources: [Gazit Y., Nahir AM, Grahame R, Jacob G. "Dysautonomia in joint hypermobility syndrome" Am J Med. 2003 Jul; 115 (1): 33-40. Comment in: Am J Med 2004 Jun 1; 116 (11):783; author reply 783–4.]

"Physicians propose that these syndromes occur together due to abnormal connective tissue in dependent blood vessels in those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressure. Simply put, this connective tissue abnormally allows excessive amount of blood to pool in these patient's lower limbs when they stand."

Resource: [Rowe et al. 1999]

Sleep complaints are frequently reported by patients with Marfan and Ehlers-Danlos syndrome (EDS). We examined the exact nature of sleep complaints in these patients. Periodic limb movements were reported more often in EDS (67%, p = 0.02) than in Marfan (27%, p = 0.25) compared to controls (8%). Pain and back complaints were highly presented in both groups, but most pronounced in EDS patients. Our study calls for greater attention to the presence of apnea, pain and periodic limb movements in these patients. 

Resources:  [Verbraecken J et al. "Evaluation for sleep apnea in patients with EDS and Marfan: a questionnaire study." Clin Genet. 2001 Nov; 60 (5): 360–5.]

All patients should see a geneticist to determine the specific type of EDS that they have, but patients considering pregnancy must receive genetic counseling so that they can make informed decisions. In addition to concern about passing EDS on to a child, a woman with EDS has an increased risk of miscarriage, premature rupture of membranes, premature births, cervical incompetence and pre-mature labor. During pregnancy there is an increase in the hormone, relaxin. Relaxin causes the connective tissue to become looser, thus increasing joint laxity perinatally. This can be so severe that walking is impossible, and causes postpartum complications. Some forms of EDS can cause serious complications such as bleeding and tearing during childbirth. Those with Vascular Type also face the possibility of uterine rupture and hysterectomy.

In connection with a natural delivery, several women with EDS have experienced incontinence, weak pelvic floor, prolapse of the uterus, sprained joints of the pelvis, separation of the symphysis pubis (the joint between the two pubic bones in the frontal lower part of the pelvis) and rupture of the rectal musculature. Some doctors recommend a cesarean section so that the mother's fragile tissue and/or pelvis are not strained. In connection with the planning of a delivery the doctor and the woman should discuss advantages and disadvantages of a natural delivery compared to a cesarean section.

Hypermobility of the joints of the bones in the middle ear (malleus, incus and stapes) creates problems with effective sound conduction across the middle ear. This loss of energy in route to the inner ear leads to a mild to moderate conductive hearing loss. Because the inner ear is also responsible for balance, improper function leaves some affected with bouts of dizziness. Problems with speech can occur: articulation, swallowing, hoarseness/weak voice and fluency. [Amanda Jenner, Lynne Shields, PhD "Speech and Language Issues."]

The safe and effective way of treating mild to moderate hearing impairment which can occur in EDS is with hearing aid and necessary additional aids. There is a much more common inherited disorder of hearing known as otosclerosis which can be easily confused with the type of hearing impairment that is seen in EDS. It is vitally important for the ear surgeon to be able to differentiate between the two as the hearing loss in both is due to abnormality of the sound conduction across the middle ear. The standard treatment for otosclerosis is an operation called, a "stapedectomy." However, an attempt to undertake a stapedectomy on an EDS patient could easily end in disaster with total loss of hearing and a severe disruption of balance. [M. Hawthorne, FRCS-ENT Surgeon. "Hearing Impairment and EDS."]

A delay in the onset of walking is common in individuals with familial ligamentous laxities. Some of the complaints of ligamemtary laxity are hallux valgus with metatarsus primus adductus, hallux limitus, flexor stabilization-type hammertoes, plantar fascitis, hindfoot degenerative joint disease, derangement of the knee, clubbed foot, rotated hips, increased femoral anteversion, webbed toes, curled/clawtoes, in-toeing or out-toeing, and flatfeet.

Complaints of foot and leg pain and fatigue are common, especially cramping of muscles, particularly at night. Pain is a significant problem.  Atrophy caused because of low muscle tone. Protective and supportive measures such as molded ankle foot orthoses many be necessary to support the child with ligamentous laxity for ambulation and to prevent injuries. Agnew P. "Evaluation if the child with ligamentous laxity.

Resource:  " Clin Podiatr Med Surg 1997 14 (1): 117–30.]

There are no studies to refer to about what effects nutrition, vitamins and herbal supplements have on the EDS patient. However, many EDS patients have had some benefits from certain diets, vitamins (especially vitamin C), zinc, magnesium, glucosamine, chondroitin, etc. This is an individual choice. Before starting any new treatment or supplements, always seek a consultation and advice from your medical doctors concerning the effects of these supplements. There may be interactions to be aware of.

Intracellular erythrocyte magnesium (RBC Mg) for muscle cramps and migraines were more frequent in Mg-deficient patients. Low potassium is likely to cause muscle weakness and even paralysis.

Resources: [Coghlan HC, Natello G. "Erythrocyte magnesium in symptomatic patients with primary mitral valve prolapse: relationship to symptoms, mitral leaflet thickness, joint hypermobility and autonomic regulation." Magnes Trace Elem. 1991–92;10(2-4):205–14.]

Chronic recurrent headaches may constitute the neurologic presentation of EDS in the absence of structural, congenital or acquired CNS lesions that correlate with their symptoms. Individuals with EDS may be prone to migraine due to an inherent disorder of cerebrovascular reactivity or cortical excitability. Additional studies are needed to elucidate the pathogenesis of headaches in EDS. 

Resource:  [De Jacome. "Headache in EDS." Cephalalgia 1999 Nov; 19 (9): 791.]

There are many Chiari patients who also have EDS. An added caution is needed due to the diagnosis of EDS. Chiari is typically treated in one of two ways: drug management and/or surgery. With EDS, the surgical protocol must be altered to protect connective tissue, deal with arachnoid scarring or adhesions and prevent cranial-cervical instability. The surgical techniques are different, too. They are designed to protect fragile tissues and prevent or minimize bleeding, and post operatively, there is more emphasis on preventing or fixing would dehiscence. Seek out and consult with Chiari-experts before undergoing any treatment or surgery. It is generally not an emergency, unless you have any of the three red flag symptoms: choking, breathing problems or drop attacks. Those indicate more severe brainstem involvement, so don't delay in seeking treatment for them. Resource(Grubb 2002 - Rowe er.al 1999)

Hereditary disorders of connective tissue may present with Chiari I malformation, occipitoatlantoaxial hypermobility and functional cranial settling. C. Francomano, T. Milhorat, P. Bolognese, M. Nishikawa, N. McDonnell. We report an association of hereditary disorders of connective tissue (HDCT) and Chiari malformation 1 (CM1), presenting with lower brain stem symptoms attributable to occipito-atlantoaxial hypermobility and functional cranial settling. The prevalence of hereditary disorders of connective tissue (HDCT) was determined in a prospectively collected cohort of 2,813 patients with CM1. The diagnosis of Ehlers-Danlos syndrome (EDS) or other HDCT was made in 357 of 2,813 of patients with CM1 (12.7%). The clinical features of HDCT/CM1 were distinguished from those of CM1 alone by clinical stigmata of HDCT, a greater female preponderance (7:1 vs. 3:1),  a greater incidence of lower brain stem symptoms (0.43 vs. 0.05), retroodontoid pannus formation (0.71 vs. 0.16) and hypoplasia of the oropharynx (0.45 vs. 0.02). In patients with HDCT/CM1, upon sitting or standing there was reduction of the basal-dens interval (3.6 mm), enlargement of the basal-atlas interval (3.0 mm) reduction of the clivus-axis angle(10.8o), reduction of clivus-atlas angle (5.8o) and reduction of the atlas-axial angle (5.3o). These changes were reducible by cervical traction or returning to the supine position. In normal controls and patients with CM1 alone, these measurements did not change with position. The identification of HDCT in 12.7% of patients with CM1 establishes an association between these previously unrelated disorders. Patients with HDCT and symptoms suggestive of CM1 should be evaluated with brain MRIs in the supine and upright positions. Full paper available from http://bit.ly/xesPlJ.

Splice site mutations in the COL1A2 gene of type I collagen can give rise to forms of Ehlers-Danlos syndrome (EDS) because of partial or complete skipping of exon 6, as well as to mild, moderate or lethal forms of osteogenesis imperfecta as a consequence of skipping of other exons. We identified three unrelated individuals with a rare recessively inherited form of EDS (characterized by joint hypermobility, skin hyperextensibility and cardiac valvular defects). In two of them, COL1A2 messenger RNA (mRNA) instability results from compound heterozygosity for splice site mutations in the COL1A2 gene, and, in the third, it results from homozygosity for a nonsense codon. The splice site mutations led to use of cryptic splice donor sites, creation of a downstream premature termination codon and extremely unstable mRNA. In the wild-type allele, the two introns (IVS11 and IVS24) in which these mutations occurred were usually spliced slowly in relation to their respective immediate upstream introns. In the mutant alleles, the upstream intron was removed, so that exon skipping could not occur. In the context of the mutation in IVS24, computer-generated folding of a short stretch of mRNA surrounding the mutation site demonstrated realignment of the relationships between the donor and acceptor sites that could facilitate use of a cryptic donor site. These findings suggest that the order of intron removal is an important variable in prediction of mutation outcome at splice sites and that folding of the nascent mRNA could be one element that contributes to determination of order of splicing. The complete absence of pro alpha 2(I)chains has the surprising effect of producing cardiac valvular disease without bone involvement.

Resources[Schwarze U et al. "Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway." Am J Hum Genet. 2004 May;74(5):917–30. Epub 2004 Apr 09.]

Subcutaneous bleeding is caused by collagen abnormalities in the vessel wall. The high frequency of a bleeding tendency in Ehlers-Danlos patients with normal tests for haemostasis (83%) supports the conventional explanation for this clinical feature. It shows that the defects in the structural integrity of skin and blood vessels lead to easy bruising.

Resources[Anstey A, Mayne K, Winter M, Van de Pette J, Pope FM. "Platelet and coagulation studies in Ehlers-Danlos syndrome." Br J Dermatol. 1991 Aug;125(2):155­63). Disorders of Vascular Fragility, Reed E. Pyeritz MD, PhD Vol 29; (6): 2001.]

Pepin M, Schwarze U, Superti-Furga A, Byers PH. “Clinical and genetic features of Ehlers-Danlos syndrome type IV, the Vascular Type.” N Engl J Med. 2000 Mar; 342(10):673–80. Erratum in: N Engl J Med 2001 Feb 1;344(5):392.

Structural abnormalities of the gastrointestinal tract are common in EDS due to the fragility and extensibility of the tissue. Hiatal hernia, gastric, duodenal and colonic diverticula may occur. Other features which have been demonstrated are visceroptosis (protrusion of the contents of the abdomen), slow motility, delayed gastric emptying, gastric atony (lack of contraction of the stomach), recurrent abdominal pain, gastroesophageal reflux disease (GERD), megaoesophagus, irritable bowel, constipation, diarrhea, megacolon, bleeding, ruptures and perforations.

Resources: Solomon JA et al. "GI Manifestations of EDS." Am J Gastroenterol 1996 Nov; 91 (11): 2282–8. Available from http://bit.ly/UzmCCX.

Poken-Harris et al. "The Prevalence of Non-Surgical Complications in the EDS."

Primary muscular hypotonia may occur and may cause delayed motor development, problems with ambulation and mild motor disturbance. Fatigue and muscle cramps are relatively frequent. Physical therapy can teach certain exercise techniques that can strengthen muscles around joints and may help to prevent or limit damage. Hydrotherapy (taking place in water) may be less damaging to joints.

Hearing impairment and/or sensitivity can occur due to the possibility of hypermobility of the joints between these bones of the middle ear (malleus, incus  and stapes) can create problems with effective sound conduction across the middle ear. This loss of energy in route to the inner ear leads to a mild to moderate conductive hearing loss. Because the inner ear is also responsible for balance, improper function leaves some affected with bouts of dizziness. 

Resource[Amanda Jenner, Lynne Shields, PhD. "EDS Speech and Language Issues."]

The safe and effective way of treating the mild to moderate hearing impairment which can occur in EDS is with hearing aid and necessary additional aids. There is a much more common inherited disorder of hearing know as oloscterosis which can be easily confused with the type of hearing impairment that is seen in EDS. It is vitally important for the ear surgeon to be able to differentiate between the two. As the hearing loss in both is due to abnormality of the sound conduction across the middle ear. The standard treatment for oloscterosis is an operation called, a "stapedectomy". However, do not attempt to undertake a stapedectomy on an EDS patient as it could easily end in disaster with total loss of hearing and a severe disruption of balance.

Resource[M. Hawthorne, FRCS. "Hearing Impairment and EDS."]

There is no known medical treatment to increase the production of type III collagen. However, ascorbic acid (1 to 2 grams per day) may increase the synthesis of collagen and therefore provide slightly more of the normal type III collagen.

Most drugs, including aspirin, can be used with the approval of a physician. Drugs that induce hypertension are not a good idea. Aspirin can be used when blood vessels are narrowed by a dissection, particularly in vessels that feed the brain, to maintain flow. So there is never a never with medications and it is always a matter of appropriate care. Answered by Peter Byers, MD and Melanie Pepin, MS, CGC

With respect to inadvertently elevating blood pressure, patients/physicians should be mindful of the impact that certain kinds of drugs may have on those with EDS, especially those with the Vascular EDS. The possibility exists that the Vascular patient may have undiagnosed aneurysms.

"Over-the-counter" medications that include decongestants can drive your blood pressure up. These are used in cold/sinus/cough preparations. Pure "antihistamines" without are generally safe, as are several prescription preparations. Control of high blood pressure may help prevent some aneurysms. Control of all risk factors associated with atherosclerotic disease (diet, exercise, cholesterol control) may help prevent aneurysms or their complications. [Medline Plus Medical Encyclopedia entry on Aneurysm]

In Autosomal Dominant inheritance, only one gene from the parent needs to be functioning improperly for an individual to be affected. When an affected person has children, there is a 50% chance with each pregnancy that the parent will pass on the changed gene to his/her children. Therefore there is a 50–50 chance that the child will be affected, regardless of the sex of the child. A person who does not carry the changed gene is not affected and cannot pass the gene on to his/her children. EDS types that are inherited in the autosomal dominant fashion include the Classical Type , Hypermobility Type, Vascular (VEDS) Type and Arthrochalasia Type. Most cases of EDS seem to follow the autosomal dominant pattern of inheritance.

More Information about Autosomal Dominant at medterms.com.

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