MEDI7212 Lecture 58: W8 - Connective tissue disorders (children)
CONNECTIVE TISSUE DISORDERS (CHILDREN)
Marfan syndrome
Definition
• Connective tissue disorder leading to ocular, skeletal & cardiovascular abnormalities
Genetics
• Autosomal dominant mutation of FBN1 (glycoprotein fibrillin-1) gene
• FBN1 gene normally is the main component of microfibrils to help anchor cells to the
extracellular matrix
• 100% penetrance of mutation
Clinical
manifestations
• Cardiovascular system
• Major findings include aortic aneurysm & valvular prolapse
• Pathology of the aortic root & ascending aorta
o Aortic media is affected preferentially in areas subject to most
hemodynamic stress
o Aorta progressively dilates or acutely dissects
o Aortic root dilates in 50% (children) or 60-80% (adults) causing aortic
regurgitation, thus diastolic murmur heard over the aortic valve
• Redundant cusps & chordae tendineae may cause mitral valve prolapse or
regurgitation; mitral valve prolapse causes systolic click & late systolic murmur
• Bacterial endocarditis may develop on affected valves
• MSK system
• Patients are taller than average for age & have long limbs
• Arachnodacyly (disproportionate, long, thin digits) is indicated by thumb sign
(distal phalanx of thumb protrudes beyond edge of clenched fist)
• Sternum deformity - pectus carinatum (outward displacement) or pectus
excavatum (inward displacement)
• Joint hyperextensibility
• Genu recurvatum (backward curvature of legs at knees)
• Pes planus (flat feet)
• Kyphoscoliosis
• Diaphragmatic and inguinal hernias
• High-arched palate
• Ocular system
• Weak ciliary zonules (connective tissue strands that suspend the lens)
• Ectopic lentis (subluxation or upward dislocation of lens)
• Iridodonesis (tremulousness of iris)
• High grade myopia
• Sometime spontaneous retinal detachment
• Pulmonary system
• Cystic lung disease
• Recurrent spontaneous pneumothorax
• CNS
• Dural ectasia (widening dural sac surrounding spinal cord) most commonly in
lumbosacral spine
• Headache, lower back pain or neurological deficits + bowel or bladder
weakness
Diagnosis
• Diagnosis (2010 Revised Ghent Nosology)
• Clinical criteria
• Genetic testing (FBN1 gene)
• ECHO/ MRI (measure aortic root, detect valve prolapse)
• Slit-lamp exam (lens abnormalities)
• XR of skeletal system
• MRI of lumbosacral spine (dural etasia)
• Differentials
• Homocystinuria - differentiate by detecting homocystine in urine
Document Summary
Definition: connective tissue disorder leading to ocular, skeletal & cardiovascular abnormalities. Genetics: autosomal dominant mutation of fbn1 (glycoprotein fibrillin-1) gene. Fbn1 gene normally is the main component of microfibrils to help anchor cells to the extracellular matrix. Sternum deformity - pectus carinatum (outward displacement) or pectus excavatum (inward displacement) Iridodonesis (tremulousness of iris: pulmonary system, cystic lung disease, recurrent spontaneous pneumothorax, cns, dural ectasia (widening dural sac surrounding spinal cord) most commonly in lumbosacral spine, headache, lower back pain or neurological deficits + bowel or bladder weakness. Diagnosis: diagnosis (2010 revised ghent nosology, clinical criteria, genetic testing (fbn1 gene, echo/ mri (measure aortic root, detect valve prolapse, xr of skeletal system, mri of lumbosacral spine (dural etasia) Slit-lamp exam (lens abnormalities: differentials, homocystinuria - differentiate by detecting homocystine in urine. Definition: hereditary collagen disorder characterised by articular hypermobility, dermal hyperelasticity and widespread tissue fragility.
