复旦大学：《医学遗传学 Medical Genetics》课程教学资源（学习报告）Epilepsy_review_paper_B

pIIe psy Introduction Epilepsy is chronic neurological disorder Characterized by recurrent unprovoked seizures Seizures are transient signs of abnormal, excessive or synchronous neural activity 50 million worldwide. 90% in developing countries More in young children and over 65, but can occur anytime. Epilepsy can only be controlled not cured However 30 are not able to be controlled Not a single disorder but convergence of vastly divergent symptoms involving episodic abnormal electrical activity in brain Classified by Observable manifestations Location Identified medical syndromes Trigger

E p i l e p s y Introduction • Epilepsy is chronic neurological disorder • Characterized by recurrent unprovoked seizures • Seizures are transient signs of abnormal, excessive or synchronous neural activity • 50 million worldwide. 90% in developing countries • More in young children and over 65, but can occur anytime. • Epilepsy can only be controlled, not cured. • However 30 % are not able to be controlled. • Not a single disorder but convergence of vastly divergent symptoms involving episodic abnormal electrical activity in brain. • Classified by – Cause – Observable manifestations – Location – Identified medical syndromes – Trigger

Can be partial or generalized Absence seizure 40 different types Children behaviors include Inattentive staring Benign shudders Nodding, rocking head banging Corot。200 Tr o(se Conversion disorder flailing and jerking of the head) Management of seizure Prevent patient from self-injury Snoring indicates normal breathing If reguritation occurs, place in recovery position Emergency medical treatment needed for >5 mins Do not place objects in mouth Let seizure take its own course Surgery very rare, for those meds cannot control - or tumor or arteriovenous malformations

• Can be partial or generalized • 40 different types • Children behaviors include – Inattentive staring – Benign shudders – Nodding, rocking, head banging – Conversion disorder (flailing and jerking of the head) Management of seizure • Prevent patient from self-injury • Snoring indicates normal breathing • If reguritation occurs, place in recovery position • Emergency medical treatment needed for >5 mins • Do not place objects in mouth. • Let seizure take its own course • Surgery very rare, for those meds cannot control – or tumor or arteriovenous malformations

Patients often exhausted and confused Occasionally, patients lose bladder and or bowel contro Anticonvulsant medication Often lifelong Can have major effects on quality of life Earliest is bromide(1857) Potassium bromide - impotence in men. Phenobarbital (1912) Phenytoin(1930) Currently about 20 common ones The genetics Mutations in several genes linked to some types of epilepsy Mainly in protein subunits of voltage-gated and ligand-gated ion channels Some inherited ones believed to be genes for: sodium ion channels(stay open too long Glutamate neurotransmitter(Ca2+ GABA

• Patients often exhausted and confused • Occasionally, patients lose bladder and or bowel control • Anticonvulsant medication – Often lifelong – Can have major effects on quality of life – Earliest is bromide (1857) – Potassium bromide – impotence in men. – Phenobarbital (1912) – Phenytoin (1930) – Currently about 20 common ones The genetics • Mutations in several genes linked to some types of epilepsy • Mainly in protein subunits of voltage-gated and ligand-gated ion channels • Some inherited ones believed to be genes for: – sodium ion channels (stay open too long) – Glutamate neurotransmitter (Ca2+) – GABA

Chromosome 10 Partial epilepsy -originally thought to be from head injury, vascular disease or brain development problems Chromosome 10 Single family study(8-19 yrs old onset for 11 members Humming noise before seizure twitching on one side Actual mutation not found but narrowed to Chromosome 10 Extra X, Y and epilepsy · Extra x in women Extra y in men · XO women Sex chromosome extra or lacking thereof linked with higher epilepsy counterparts than their healthy counterparts

Chromosome 10 • Partial epilepsy - originally thought to be from head injury, vascular disease or brain development problems • Chromosome 10 • Single family study (8-19 yrs old onset for 11 members) • Humming noise before seizure, twitching on one side. • Actual mutation not found, but narrowed to Chromosome 10 Extra X, Y and epilepsy • Extra X in women • Extra Y in men • XO women • Sex chromosome extra or lacking thereof, linked with higher epilepsy counterparts than their healthy counterparts

Chromosome 15 Microdeletions in chromosome 15q133 Deletions found only in patient and not in controls Study in 2009 in Nature Genetics Chromosome 3. 18 Febril seizures most common of children 2-5% children affected in USA Mostly no permanent damage but small develop epilepsy later in life French family study -4 Generation Chromosome 3 and 18 Gene on 18 believed to be modifier Exact gene not found

Chromosome 15 • Microdeletions in chromosome 15q13.3 • Deletions found only in patient and not in controls. • Study in 2009 in Nature Genetics Chromosome 3, 18 • Febril seizures most common of children. • 2-5% children affected in USA. • Mostly no permanent damage, but small develop epilepsy later in life. • French family study – 4 Generation • Chromosome 3 and 18. • Gene on 18 believed to be modifier. • Exact gene not found

Chromosome 8p Progressive epilepsy with mental retardation (EPMR) is autosomal recessive disorder EPMR mapped to chromosome 8p23 Childhood onset epilepsy and mental retardation(ages 5-10) tonic-clonic seizures. EPMR in telomeric region of 8p Chromosome 6 LaFora disease - aggressive epilepsy Presence of glycogen -like Lafora bodies in brain Autosomal recessive mutation of epm2a on chromosome 6 Gene produces phosphatase laforin Loss of function epm2a function results disease

Chromosome 8p • Progressive epilepsy with mental retardation (EPMR) is autosomal recessive disorder • EPMR mapped to chromosome 8p23. • Childhood onset epilepsy and mental retardation (ages 5-10) tonic-clonic seizures. • EPMR in telomeric region of 8p Chromosome 6 • LaFora disease – aggressive epilepsy • Presence of glycogen-like Lafora bodies in brain • Autosomal recessive mutation of EPM2A on chromosome 6 • Gene produces phosphatase laforin • Loss of function EPM2A function results in disease

Ring chromosomes RC20-not all develop epilepsy, but present in many Refractory epilepsy Fusion by 2 arms of the chromosome during development RC17 also found Deletion at 17p 17q telomere undeleted Ring chromosome and epilepsy linkage? Conclusion Many types of epilepsy Many chromosomes many genes Not all found or known Not all genotype problems results in phenotype

Ring Chromosomes • RC20 – not all develop epilepsy, but present in many. • Refractory epilepsy • Fusion by 2 arms of the chromosome during development • RC17 also found • Deletion at 17p • 17q telomere undeleted. • Ring chromosome and epilepsy linkage? Conclusion • Many types of epilepsy • Many chromosomes, many genes • Not all found or known • Not all genotype problems results in phenotype

Genetics Review paper Proff Liu wen Written by: RADY Student no: 08301016046

Genetics Review paper Proff.LIU WEN Written By:RADY Student no:08301016046