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MG8 Medical Genetics
Syndromes and Diseases
Toronto Notes 2019
Gower’s Sign
Child uses hands to “climb up” the legs to move from a sitting to a standing position
Other Single Gene Disorders
CYSTIC FIBROSIS
• seeRespirology,R12andPediatrics,P80 SICKLE CELL DISEASE
• seeHematology,H20
DUCHENNE MUSCULAR DYSTROPHY
Epidemiology
• 1:4,000males
Etiology
• onetypeofmusculardystrophycharacterizedbyprogressiveskeletalandcardiacmuscledegeneration • X-linkedrecessive:1/3spontaneousmutations,2/3inheritedmutations
• missingstructuralprotein(dystrophin)→musclefibrefragility→fibrebreakdown→necrosisand
regeneration
Clinical Presentation
• proximalmuscleweaknessbyage3,positiveGower’ssign,waddlinggait,toewalking
• pseudohypertrophyofcalfmuscles(musclereplacedbyfat)andwastingofthighmuscles
• decreasedreflexes
• non-progressivedelayedmotorandcognitivedevelopment(dysfunctionaldystrophininbrain) • cardiomyopathy
Diagnosis
• moleculargeneticstudiesofdystrophingene(DMD)(firstline) • familyhistory(pedigreeanalysis)
• increasedCK(50-100xnormal)andlactatedehydrogenase
• elevatedtransaminases
• musclebiopsy,EMG
Management
• supportive(e.g.physiotherapy,wheelchairs,braces),preventobesity
• cardiachealthmonitoringandearlyintervention
• bonehealthmonitoringandintervention(vitaminD,bisphosphonates) • steroids(e.g.prednisoneordeflazacort)
• surgical(forscoliosis)
• genetherapytrialsunderway
Complications
• patientusuallywheelchair-boundby12yrofage
• earlyflexioncontractures,scoliosis,osteopeniaofimmobility,increasedriskoffracture
• deathduetopneumonia/respiratoryfailureorcongestiveheartfailurein2nd-3rddecade
