Inherited Disorders Of Connective Tissues: Osteogenesis Imperfecta, Ehler’s Danlos Syndrome And Marfan’s Syndrome
Ehlers- Danlos Syndrome
A General Overview
The term, connective tissue includes cartilage, bone, tendons, fascia, ligaments and vascular walls. The connective tissue consists mainly of fibrous proteins- collagen and elastin and the amorphous complex carbohydrates, hyaluronic acid, proteoglycans and glycoproteins together called the ground substance. Functions of connective tissue include:
- Formation of an elastic covering, e.g. dermis
- Protection of vital structures, e.g. skull
- Acting as layers of aiding muscular action, e.g. long bones, and
- Provision of deformable elastic cushions to bear stress and aid in joint movement, e.g. cartilage.
Collagens are a class of proteins, each being determined by a single gene. Two major types are pericellular and interstitial collages. Pericellular collagen (types IV and V) occurs in basement membranes and intercellular tissues. The major collagen of skin, bones, articular cartilage, tendons and fascia is interstitial collage (types I, II and III). The collagens are formed from procollagens by complex enzymatic processes.
Developmental disorders involving the collagens may be hereditarily transmitted. The manifestation of severity differ on account of differences in penetrance and expression of single genes or genetic heterogenicity.
Major Disorders Of Collagens
Ehlers- Danlos Syndrome: This is a disorder of types I and III interstitial collagen. Clinical features include hyperextensibility of the skin, laxity of joints with tendency to subluxate, purpura, bruises, subcutaneous nodular calcification and violaceous subcutaneous nodules called molluscoid pseudotumours, delayed wound healing and kyphoscoliosis. The genetics of this disorder is heterogenous and on this basis, Ehlers-Danlos syndrome may be subclassified into autosomal dominant, autosomal recessive and X-linked types.
In this disorder, a wide spectrum of clinical abnormalities exists. The condition is inherited as autosomal dominant.
Bony Abnormalities: These include disproportionately long limbs compared to the trunk (dolichostenomelia), arachnodactyly (spider fingers), pectus excavatum, kyphoscoliosis, increased joint laxity, recurrent dislocations, genu recurvatum and flat feet.
Ocular lesions: Classical feature is ectopia lentis occurring in 50% of cases, the displacement of the lens in upwards, unlike as in traumatic dislocation in which the dislocation is downwards. Other features include high myopia and retinal detachment.
Cardiovascular lesions: Dilatation of the aortic root, aortic regurgitation, aneurysms of the ascending aorta and sinus of Valsalva, dissecting aneurysms and mitral valve prolapsed may occur. Respiratory manifestations include lung cysts and recurrent pneumothorax.
Differential diagnosis: Marfan’s syndrome closely resembles homocystinuria which may present with skeletal and ocular abnormalities similar to those of Marfan syndrome. The urine shows homocystine.
Eunuchoid Features: These may be mistaken for Marfanoid features. In the former, there is no arachnodactyly and other feature of hypogonadism are present.
Diagnosis: Strong clinical suspicion is essential for diagnosis. If the terminal phalanx of the thumb projects beyond the medial border of the closed first, it suggests Marfan syndrome.
Treatment: No treatment is curative. Aortic lesions, joint lesions and ocular lesions are treated on their own merits. Propranolol may help in reducing the risk of aortic dissection.
© 2014 Funom Theophilus Makama