复旦大学：《医学遗传学 Medical Genetics》课程教学资源（学习报告）medical genetics presentation - myotonic dystrophy

MYOTONIC DYSTROPHY Angelika Kaakunga 12301016021

MYOTONIC DYSTROPHY Angelika Kaakunga 12301016021

Inherited disorder Onset can occur from any age Severity varies widely among affected people g A Expressionless and swanlike neck Slap jaw and ptosis Frontal balding and ptosis

• Inherited disorder • Onset can occur from any age • Severity varies widely among affected people Fig 1

Major Effects of Myotonic Dystrophy Fig 2. Cognitive Function: Intellectual Bone: Anomalies impairment, behavioral and psychological disorders, excessive Cardiovascular System daytime sleepiness Heart condition abnormalities arrhymias, cardiomyopathy Vision: Cataracts, retinal damage Gastrointestinal Tract: Swallowing Endocrine System: Diabetes, low issues, abdominal pain, irritable bowel thyroid hormone levels syndrome, constipation/diarrhea, poor nutrition and weight loss, chronic Respiratory System: Breathing infections dificulties, aspiration, sleep apnea nigh risk pneumonia Muscle: Weakness, wasting (atropy) myotonia, pain Skin: Pilomatrixoma Reproductive System in Women Immune: Hypogammalobulinemia Weakened uterine muscle pregnancy-related complications, and Reproductive System in Men gynecological problems Low testosterone levels, erectile dysfuntion, testicular failure and gonadal atrophy

epidemiology Affects 1 in 8000 people worldwide EXAMPLES 1in100000 3-15in100.000 1in500 (Japan) (Europe) (Quebec) Founder effect

Epidemiology • Affects 1 in 8000 people worldwide

Genetics Autosomal dominant Fg3 normal repeats Disorder Notable differences in CTGCTGCTGCTGCTGCTG GACGACGACGACGAC GAC sequence repeats Two types(symptoms may overlap 50 20g Both caused by mutations in different CTGCTGCTGCTG CTGCTG CTGCT G CTGCTGCTG CT CTO CTGCTOCTOCTGC1O GACGACGAC GAC GACGACGAC GACGACGACGAC GACGACOACGACGACGACGAC genes 山山山山山 山山山山山山u

Genetics • Autosomal Dominant Disorder • Notable differences in sequence repeats • Two types (symptoms may overlap) • Both caused by mutations in different genes

Normal DMPK Transcript Mutant DMPK Transcript 三三 (CUG)n expansion pre-mRNP△(CUG)5—3 EXP protein RNA EXP protein processing recruitment RNA processing 5- 3 nuclear EXP binding site mutant mRNP EXP/DMPK RNA foci normal 5 3 mRNP (A)n export export blocked NPC NUCLEUS EXP CYTOPLASM recruitment 5 3 cytoplasmic EXP binding site

Inheritance Autosomal dominant Affected Unaffected father mother Fig 5 Diagnosed at 55 Cataracts 120 repea Diagnosed at 48y Diagnosed at 50y Grp myotonia Bilateral cataracts Facial weaknes 500 repeats Myotonia Cardiac problems 700 repeats Diagnosed at birth Facialweakness Severe neonatal hypotonia repeat Affected Unaffected Unaffected Affe son daughter son daughter Unaffected Affected

Inheritance

Myotonic Dystrophy Frontal balding Cataracts Ptosis and due to weakn nuscle Wasting of cleidonastoid nuscle Gynec。 nastia Difficulty in releasing grasp Myotonia c。 genito ( Thomsen·: disease) N Percussion myotonic reaction: thumb moves sharply into cussion of thenar muscles and returns to initial position slowly Electromyogram shower Myotonia and muscular over ffects evoked by needle insertion both males and females

Management

References Udd B, Meola G, Krahe R, et al. ( June 2006). 140th ENMC International Workshop: Myotonic Dystrophy DM2/PROMM and other myotonic dystrophies with quidelines on management. Neuromuscul. Disord. 16(6): 403-13 Myotonic dystrophy(November 2010). Your Guide to understanding Genetic Conditions Genetics Home Reference http://ghr.nim.nihgov/condition/myotonic-dystrophy.u.s National Library of Medicine Beth Hogans, MD; Steven Novella, MD(1998) Myotonic Dystrophy http://medicine.yaleedu/neurology/divisions/neuromuscu ar/md. aspx. Neurology, Yale School of Medicine

References • · Udd B, Meola G, Krahe R, et al. (June 2006). "140th ENMC International Workshop: Myotonic Dystrophy DM2/PROMM and other myotonic dystrophies with guidelines on management". Neuromuscul. Disord.16 (6): 403–13 • · Myotonic dystrophy (November 2010). “Your Guide to understanding Genetic Conditions”. Genetics Home Reference. http://ghr.nlm.nih.gov/condition/myotonic-dystrophy .U.S. National Library of Medicine • · Beth Hogans, MD; Steven Novella, MD (1998). “Myotonic Dystrophy” http://medicine.yale.edu/neurology/divisions/neuromuscul ar/md.aspx . Neurology, Yale School of Medicine