Inpatient & Outpatient Medications
Wound healing may be improved in patients with Ehlers-Danlos syndrome (EDS) with vitamin C supplementation above the recommended daily allowance (see Medical Care). Prophylaxis for subacute bacterial endocarditis may be indicated in the presence of mitral valve prolapse as in classical EDS type I.
Deterrence/Prevention
Protecting joints and minimizing joint injury helps patients with Ehlers-Danlos syndrome reduce pain, conserve energy, and maintain an active lifestyle.
Activities that involve overextension of the joints should be avoided.
Minimize the risks of slips and falls in the home by keeping walkways and corridors clear of toys and other small items. The use of throw rugs is not recommended.
If reaching or stretching causes pain or an increased risk of subluxation and/or dislocation of the joints, consider using devices such as long–handled combs and reachers to help patients accomplish daily tasks. Consider arranging home storage areas to keep frequently used items within easy grasp. [9]
Complications
Complications are related to the primary pathophysiology and include joint dislocations, wound healing problems, and scarring. Individuals with vascular-type Ehlers-Danlos syndrome (type IV) are at risk for spontaneous arterial rupture, bowel perforation (especially the sigmoid colon), and other hollow organ perforation.
Prognosis
Median life expectancy for patients with vascular-type Ehlers-Danlos syndrome (EDS) (type IV) is 50 years. In patients with other EDS types, life expectancy is usually within the normal range for the population. Patients with vascular-type EDS (type IV) caused by null mutations in the COL3A1 gene often have a milder form of EDS than do type IV patients whose condition is due to missense and splicing mutations. The former individuals may have a longer lifespan; hence, a delayed onset of vascular complications is seen in this null mutation EDS type. [42]
Patient Education
The diversity and complexity of Ehlers-Danlos syndrome (EDS) serve to highlight several important principles of clinical human genetics. These principles must be accurately conveyed to and understood by the family members through genetic counseling.
Genetic heterogeneity illustrates that mutations in different genes can produce the same phenotype. For example, classical-type EDS (type I) can result from mutations in two collagen genes, either COL5A1 (bands 9q34.2-34.3) or COL5A2 (band 2q32.3).
Variable expression (ie, variability in severity of disease expression) is a hallmark of autosomal dominant conditions. Autosomal dominant EDS exhibits both intrafamilial and interfamilial variability, which is a critical counseling issue in regard to recurrences. In addition, closely examining families for members who may not have been diagnosed in the past, is important because of a potential milder degree of expression.
An indeterminate diagnosis of a clinical type of EDS may not be possible in about 50% of patients. The clinician must tell patients when the diagnosis is either unknown or unclear, rather than guess and provide incorrect information. Types of EDS are associated with differences in modes of inheritance and long-term prognoses.
Currently, the diagnosis of only a few types of EDS can be confirmed using the practical laboratory studies available. A prevailing misconception is that specific skin biopsy findings can confirm or exclude the specific diagnosis of EDS. No specific histopathologic skin biopsy findings identify patients with EDS; therefore, skin biopsies should not be performed to confirm or exclude the diagnosis. A skin biopsy may be indicated to obtain cultured skin fibroblasts for specific biochemical and molecular studies, but most clinicians primarily rely on their knowledge and clinical diagnostic skills.
Elucidating the pathophysiology of a specific clinical disorder often leads to rethinking the phenotypic classification. For example, the previously designated EDS type IX is now known to be due to a mutation in a copper transport gene and is an allelic variant to Menkes (kinky hair) disease.
Patients should protect their joints and avoid undue trauma. Instruct patients to avoid entertaining other persons by performing maneuvers "showing off" their joint laxity. Continued excessive stretching of the joints may further exacerbate the underlying disorder.
Teach patients to avoid excessive or repetitive heavy lifting and other movements that produce undue strain or stress on already hypermobile joints.
Patients with EDS must practice meticulous dental care. Monitor dental hygiene and treat periodontitis aggressively. Gingival recession is a noted concern for vascular-type EDS (type IV).
Instruct patients with EDS to visit the ophthalmologist regularly for myopia, retinal tears, and keratoconus screening. This advice is especially important for patients with kyphoscoliosis-type EDS (type VI).
Instruct patients with EDS to avoid undue trauma to the skin and other organ systems because of poor wound healing and skin fragility. In particular, the primary care physician should strongly discourage potentially traumatic recreational activities.
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Patient with Ehlers-Danlos syndrome. Note the abnormal ability to elevate the right toe. Courtesy of Enrico Ceccolini, MD.
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Girl with Ehlers-Danlos syndrome. Dorsiflexion of all the fingers is easy and absolutely painless. Courtesy of Enrico Ceccolini, MD.
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Patient with Ehlers-Danlos syndrome mitis. Joint hypermobility is less intense than with other conditions. Courtesy of Enrico Ceccolini, MD.
Tables
Type |
Inheritance |
Previous Nomenclature |
Major Diagnostic Criteria |
Minor Diagnostic Criteria |
Classical |
Autosomal dominant |
Types I and II |
Marked skin hyperextensibility, wide atrophic scars, joint hypermobility |
Smooth, velvety skin; easy bruising; tissue fragility; molluscoid pseudotumors (calcified hematomas over pressure points, eg, elbows); subcutaneous spheroids (fat-containing cysts on forearms and shins); joint hypermobility (eg, sprains, dislocations, subluxations); flat feet; muscle hypotonia; gross motor delays; postoperative complications (eg, hernia); manifestations of tissue fragility (eg, hiatal hernia, anal prolapse, cervical insufficiency); positive family history |
Hypermobility |
Autosomal dominant |
Type III |
Generalized joint hypermobility, affecting both large (elbows, knees) and small (fingers, toes) joints; skin involvement (soft, smooth and velvety) |
Recurrent joint dislocations and subluxations of shoulder, patella, and temporomandibular joints; chronic joint pain; limb pain; musculoskeletal pain; bruising tendencies; positive family history |
Vascular *Considered most serious EDS type, owing to risk of spontaneous arterial or organ rupture |
Autosomal dominant |
Type IV |
Thin, translucent skin, easy to see vasculature through the skin, especially chest and abdomen; arterial/intestinal fragility or rupture; extensive bruising with minor trauma; characteristic facial appearance of large eyes, thin nose, lobeless ears; short stature; thin scalp hair |
Acrogeria, aging skin; decrease of subcutaneous tissue in the face and extremities; gingival recession; hypermobile small joints; tendon/muscle rupture; clubfoot; early onset varicose veins; arteriovenous fistula; carotid-cavernous fistula; pulmonary conditions, pneumothorax, pneumohemothorax; positive family history; sudden death in close relative |
Kyphoscoliosis |
Autosomal recessive |
Type VI (Lysyl hydroxylase deficiency-collagen-modifying enzyme) |
Generalized joint laxity; severe hypotonia at birth; delayed gross motor development; progressive scoliosis (present at birth); scleral fragility or ocular globe rupture post minor trauma |
Tissue fragility; atrophic scars; easy bruising; spontaneous arterial rupture; marfanoid habitus; microcornea; osteopenia; positive family history (affected sibling) |
Arthrochalasia |
Autosomal dominant |
Types VIIA and VIIB |
Congenital hip dislocation; severe generalized joint hypermobility; recurrent subluxations |
Skin hyperextensibility with easy bruising; tissue fragility with atrophic scars; muscle hypotonia; kyphoscoliosis, mild osteopenia |
Dermatosparaxis |
Autosomal recessive |
Type VIIC |
Severe skin fragility; marked bruising; saggy, redundant skin, especially of the face; scars not atrophic |
Soft, doughy skin; premature rupture of membranes; hernias (umbilical and inguinal) |
Type |
Old Nomenclature |
Protein Abnormality |
Gene Abnormality |
Chromosome Locus |
Classical |
Types I and II |
Type V collagen |
*COL5A1,COL5A2 COL1A1 |
*9q34.3 2q32.3 17q21.3 |
Hypermobility |
Type III |
Type III collagen Tenascin-XB |
COL3A1 TNXB |
2q32.2 6p21.3 |
Vascular |
Type IV |
Type III collagen |
COL3A1 |
2q32.2 |
Kyphoscoliosis |
Type VI |
Lysyl hydroxylase deficiency (some) |
PLOD1 |
1p36.22 |
Arthrochalasia |
Types VIIA and VIIB |
Type I collagen |
A: COL1A1 B: COL1A2 |
17q21.33 7q21.3 |
Dermatosparaxis |
Type VIIC |
N-proteinase |
ADAMTS2 |
5q35.3 |
