Ehlers-Danlos Syndrome

Ehlers-Danlos syndrome type II arises because of an abnormality of type V collagen, at least in some individuals. Testing for type V collagen is not so straightforward as that already done for type III collagen. The gene change that results in type II EDS is what is termed autosomal dominant in character.

Collagen abnormalities in the various forms of EDS affet the cushioning function of joints. Individuals with various forms of EDS, then, tend to 'wear out' that cushioning function faster tahn average. The joints that are most at risk are weight bearing stress is probably appropriate in an effort to preserve joint function.

All collagens require vitamin C as a confactor for their synthesis. Most forms of EDS appear to be caused by underproduction of collagen of one sort or another. Therefore, there is speculation that providing increased confactor may drive the system just a little bit and perhaps diminsh the severity of clinical features

病因學：

為先天膠原結締組織異常之遺傳疾病，俗稱鬆皮症，此症由於體內合成膠原出現障礙，以致膠原不足或品質不好，其特徵皮膚有高度伸展性，皮膚和血管較為脆弱，傷口癒合比較慢，關節活動範圍的過度增加，所以也被稱為橡皮人症候群（rubber man syndrome）。 
發生率：
約為1/150,000，很多輕微型的患者並未納入計算。  
臨床上表徵：

主要分成十一型，臨床特徵與遺傳模式不盡相同，患者以第一、二、三型佔大多數。通常為體染色體顯性遺傳。

類型	特徵	遺傳模式	突變基因
I	皮膚細薄且光滑，引人注目的高延展性，容易破皮，有疤卷煙紙般的疤痕 Cigarette paper scars 皮膚過度伸直 Hyperextensible skin 關節過度變形 Hypermobile joints 最常見二尖瓣膜脫垂，可能會發生疝氣	體染色體 顯性遺傳	COL5A
II	類似type I 但症狀較為中等	體染色體 顯性遺傳
III	關節過度變形顯著 hypermobile，關節變異比皮膚變異嚴重，皮膚柔軟但沒有疤痕，顯著的關節活動範圍增加。	體染色體 顯性遺傳
IV	皮膚薄細 Thin translucent skin到可以看見皮下血管，在骨頭突起處會產生疤痕與色素沉澱。 顯著的挫傷 Marked bruising 動脈與腸道破裂 Arterial and intestinal rupture	體染色體 顯性遺傳	COL3A1
VI	柔軟的皮膚 Soft velvet-like skin 易損的眼睛 Ocular fragility	體染色體 隱性遺傳	PLOD
IX	膀胱憩室 Bladder diverticulum 可能因輕微創傷而造成眼球破裂 可能因脊柱側凸而造成呼吸受限	X染色體 隱性遺傳	MNK

診斷：
此症的診斷主要是根據臨床症狀，也可經生化檢驗方法或基因分析方式，進行診斷膠原蛋白分子的缺損，但是相當困難與費時。

醫療照護：
目前沒有特殊的治療方法
 
外科手術
小心地評估患者是否可以手術來修補矯正骨折和關節脫臼情形，且易瘀青的患者需除其它出血性疾病的可能性。

眼睛治療
不論是成人或孩童的患者應有定期的檢查，近視是普遍會產生的情況。而第四型的患者特別會有眼睛方面受損的風險，所以需要有這方面經驗的眼科專科醫師的會診。

孕期中的患者
第四型病人及其家屬需要定期接受超音波檢查以早期發現動脈瘤，此型之女性患者懷孕時，醫師應預先告知有子宮破裂、出血及其它併發症的可能，並定期接受最詳盡之產前檢查與照顧，以避免危險併發症的發生。

皮膚的保護
因創傷或日曬引起嚴重的皮膚病變，若需縫合皮膚時可能會較為困難些，因為患者的皮膚相當的脆弱，其傷口應特別注意且預防感染的發生。 

What is EDS?

Introduction 

Ehlers-Danlos Syndrome (EDS) is a heterogeneous group of heritable disorders of connective tissue, characterised by skin extensibility, joint hypermobility and tissue fragility.   There are different types of EDS and these were reclassified into six major types in 1997 1 .   They are classified according to signs and symptoms with each type running true in a family thus an individual with one type will not have a child with a different type. 

EDS is caused by a defect in a protein called collagen, of which there are more than 30 different types.   It is a protein and is the main building block of the body providing strength and support.   Some examples are ligaments, tendons and cartilage.   Consequently, if the collagen itself is defective, it can produce many problems throughout the body.

Prevalence  

EDS is known to affect both males and females of all races and ethnic backgrounds.   The exact incidence is not known, but is estimated at 1 in 5000, however, it may be more common.

Diagnosis 

Diagnosis is based on the presenting symptoms and family history of a patient. Many EDS sufferers, however, do not fit conveniently into the definition of a specific type, and are frequently misdiagnosed. A skin biopsy may be taken to confirm the diagnosis and determine the type.   Of the six types of EDS, there is only one type, the Hypermobility type, that does not have a specific test.   In each of the other five cases, the specific gene mutation has been identified and can be tested for.   Where the Hypermobility type is suspected, it is possible to examine the collagen in the skin sample for abnormalities. 

Prognosis  

The prognosis depends largely on the type of EDS the patient has.   For instance, life expectancy in the Vascular Type (formerly type lV) is generally shortened to around 40 years due to the rupture of large blood vessels and the major organs.  Pregnancy can be life-threatening in the Classical (formerly types I and II) and Vascular Types.

SYMPTOMS 

Skin

• Hyperextensibility

Cutaneous hyperextensibility (stretchy skin) characterises all types of EDS, except for the Vascular Type (type lV), which has noticeably translucent skin with visible veins.   When skin is over-stretched it still retains normal elastic recoil and snaps back once released.   This is best tested at the neck, elbows, or knees.

• Cutaneous fragility

Easy splitting of the skin is particularly common in Classical Type.   Gaping, 'fish-mouth' or 'cigarette paper' scars follow minimal trauma over sites of bony prominence and areas prone to trauma such as the forehead, chin, elbows, knees, and shins.

• Epicanthic folds

These are additional symmetrical folds of skin at the inner aspects of the eyes producing apparent broadening of the nose.

• Molluscoid pseudotumours

These are firm, fibrous lumps measuring up to 2 - 3 cm which develop over pressure points such as the elbows and knees.

• Spheroids

Approximately one third of affected individuals describe small, firm nodules like 'ball-bearings' just beneath the skin (sub cutis).   These consist of fibrotic and calcified fat which overlay bony areas such as the shins.

• Piezogenic papules

These small, soft, skin-coloured lumps appear on the side of the heel when standing and disappear when the foot is elevated.   Although usually symptom-less they can occasionally be painful.

• Varicose veins

These are more common in many types of EDS, than in the general population.  

Joints 

Joints are hypermobile (lax) due to the extra elasticity of the ligaments resulting from the collagen abnormality.   The degree of hypermobility is assessed using the Beighton Scale 2 (see 'Ehlers-Danlos Syndrome' booklet).   A score of 5/9 or higher defines hypermobility. 

The laxity of the joints makes them susceptible to subluxation and dislocation, of which the patient often has a history.   This often occurs without significant trauma as would be necessary to cause dislocation in somebody who does not have EDS.  Those with the Vascular Type do not generally exhibit joint laxity. 

Pain is a common feature with hypermobile joints, even when skeletal X-Rays are normal.  

Bruising and Haematomas 

Easy bruising, accompanies most forms of EDS, often as a result of minimal trauma.   This implies increased fragility of dermal blood capillaries and poor structural integrity of the skin.   When bruising presents in a child it may be incorrectly attributed to non-accidental injury.

Mitral Valve Prolapse 

This is quite common and should be diagnosed by echocardiography, CT or MRI.

Less Common Features

• Arterial, uterine and intestinal ruptures may occur due to the fragility of tissues.   These ruptures are more commonly found in the Vascular Type, but also occur in other types.   Inguinal and hiatus hernias are also relatively common.
• Scoliosis (bend in the spine) may be present at birth or can develop in later life.
• Gum disease.
• Gastrointestinal diverticula.

TREATMENT AND MANAGEMENT  

This depends on the presenting symptoms but simple precautionary measures will greatly lessen the chances of accidental trauma, scarring and bruising.   It is important to carefully balance the advantages of less frequent injuries and the disadvantages of over-protection in a child. Simple measures like padding of the lower legs and elbows in children may reduce the number of injuries.

Surgery and skin suture should be undertaken with great care as fragile tissues may tear.   Sutures need to be left in longer than normal. 

Bracing may be used to support unstable joints. Orthopaedic surgery may be necessary but is not always successful.

Physiotherapy and Occupational Therapy advice may be sort to strengthen muscles and teach aids to daily living. 

Psychological  

The main problem with having Ehlers-Danlos Syndrome is that the person can look very fit and may often not be believed that they have joint pain etc.   Diagnosis is often delayed and misdiagnosis is relatively common.   Some forms of EDS may be misdiagnosed as child abuse/self-inflicted injury. Where there is severe skin involvement scarring can be severe and the person needs to learn to cope with disfigurement.