Connective tissue disorders
Marfan Syndrome
1:3,000 to 1:5,000
Pathophysiology:
Genetic mutation leads to defective fibrillin, a glycoprotein essential for connective tissue integrity
Results in abnormalities in the skeleton, cardiovascular system, and eyes
Genetics
Autosomal dominant inheritance
Mutation in the FBN1 gene on chromosome 15, which encodes fibrillin-1
Skeletal:
Dolichostenomelia (long limbs relative to trunk)
Arachnodactyly (abnormally long, slender fingers and toes)
Thoracolumbar scoliosis
Pectus deformities (pectus excavatum or pectus carinatum)
Cardiovascular:
Mitral valve prolapse
Aortic root dilatation
Ocular:
Lens dislocation (ectopia lentis)
Myopia
Cataract
Retinal detachment
Investigations:
Echocardiography to assess aortic root diameter and mitral valve function
Radiology:
Lung bullae, predisposing to pneumothorax
Management:
Regular monitoring of aortic root size with echocardiography
Aortic root dilatation, leading to aortic dissection or rupture if untreated
<4cm: Start beta-blockers and CT surveillance
5cm: Consider aortic root replacement surgery
Ehlers-Danlos Syndrome (EDS)
Pathophysiology:
A group of hereditary connective tissue disorders characterised by skin hyperelasticity, joint hypermobility, atrophic scarring, and blood vessel fragility
Caused by defects in collagen (types I and V) and extracellular matrix proteins
Genetics
Often autosomal dominant inheritance
Skin:
Hyperextensibility
Soft, velvety skin with visible underlying vessels
Joints:
Hyperflexibility
Frequent joint dislocations, particularly in the shoulder
Other:
Orthostatic intolerance
Gastrointestinal symptoms such as diarrhoea
Urinary incontinence
Impaired postural control, chronic pain, and fatigue
Complications:
Vascular rupture leading to life-threatening bleeding
Ischaemic colitis due to vascular fragility
Mitral valve prolapse
Epidermolysis Bullosa (EB)
Pathophysiology:
A group of disorders causing fragile skin that blisters easily in response to minor injury or friction
Types:
Epidermolysis Bullosa Simplex (EBS)
Dystrophic Epidermolysis Bullosa (DEB)
Junctional Epidermolysis Bullosa (JEB)
Kindler Syndrome
Genetics/Hereditary:
Can be autosomal dominant or recessive, depending on the type
Caused by mutations in genes encoding integrin, collagen, or laminin proteins
Diagnosis:
Confirmed by skin biopsy showing characteristic abnormalities
Complications:
Associated with pyloric atresia
Increased risk of developing squamous cell carcinoma (SCC) in chronic wounds
References
Salik I, Rawla P. Marfan Syndrome. [Updated 2023 Jan 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537339/
Miklovic T, Sieg VC. Ehlers-Danlos Syndrome. [Updated 2023 May 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549814/
Khanna D, Bardhan A. Epidermolysis Bullosa. [Updated 2024 Jan 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK599531/