1. PSYCHIATRY OF LD
   1. Epilepsy
      1. 22%
   2. Severe behav problems
      1. 10-15%
   3. Dementia
      1. ~12%
   4. Autism
      1. 7%
   5. Depression
      1. 4%
   6. Schizophrenia
      1. 3%
   7. OCD
      1. 2.5%
   8. Agoraphobia, Bipolar
      1. 1.5%
2. ANGELMAN'S, RETT'S (~90%), FRAGILE X ~25%, DOWN'S~5-10% ; Epilepsy -->MR : 30-40%; MR-->Epilepsy:20-25%
3. UK: total p = 20-3-/1000 ; IQ<50 in 3-4/1000
4. Main Topic 2
   1. MR
      1. IQ
      2. %
      3. CARE NEEDS
   2. MILD
      1. <70
      2. 85
      3. may need help under unusual stress
   3. Moderate
      1. <50
      2. 10
      3. need some supervision
   4. Severe
      1. <35
      2. 3-4
      3. care for self with close supervision
   5. Profound
      1. <20
      2. 1-2
      3. very few learn to care for themselves
5. Genetic etiology
   1. CLASS
      1. DISORDER
      2. GENES
      3. EPIDEMIOLOGY
      4. IQ
      5. POINTERS
   2. CHROMOSOMES
      1. DOWN'S SYNDROME
      2. <50
      3. Trisomy 21 (95%)
      4. Robersonian Translocation -5%
      5. Mosaicism- 2-5 %
      6. COMMONEST GENETIC CAUSE OF LD
      7. 1:1000 LIVE BIRTHS
      8. Maternal Age: <30 (1:2500); >40 (1:80); >45 (1:32)
      9. Cardiac AbN, EPILEPSY, ALZHEIMER'S
      10. 70-80% are born to mothers <35 yrs age
      11. Subtopic 11
   3. SEX CHROMOSOMES
      1. 1. TURNER'S
      2. 2. TRISOMY X
      3. 3. Klinefelter's
      4. 4. XYY male
      5. 1. Monosomy, 45 XO (pheno F)
      6. 1. LD is rare
      7. 2. 47, XXX
      8. 2. 70% LD , usually mild
      9. 3. 47, XXY
      10. 3. 60-70
      11. 4. 47, XYY
      12. 4. below average
      13. 2. ?increased i of Scz
      14. ALL 1:1000 [Trisomy-female, other 2-Male]
   4. AUTOSOMAL DOMINANT (phakomatoses)
      1. 1. Neurofibromatosis
      2. 2. Von Hippel- Lindau syndrome
      3. 3. Sturge- weber syndrome
      4. 4. Tuberous sclerosis
      5. polygenic
      6. -
      7. -
      8. -
      9. 4. usually SEVERE
      10. -
      11. -
      12. -
      13. 1:7000-1:10000, M=F
      14. -
      15. -
      16. depends on subtype
      17. Subtopic 17
      18. 4. LD+seizurs+ spots & 'omas (ASH LEAF ++)
      19. 3. port wine stains, LD, epilepsy, hemiparesis
   5. AUTOSOMAL RECESSIVE
      1. 1. Phenylketonuria
      2. 2. Hurler's syndrome
      3. 3. Laurence-Moon-Biedl syndrome
      4. 4. Sanfillipo disease
      5. 5. Jaubert's syndrome
      6. 1. p12( phenylalanine hydroxylase)
      7. 1. below average
      8. 2. 4p16 (A-L-iduronidase)
      9. 2. progressive LD (severe/profound)
      10. multiple loci
      11. 3. mild to mod LD
      12. 1. PREVENTATBLE, Guthrie test(postnatal), blue eyes, neuro s/s
      13. 2. Skeletal AbN, some survive to 20s
   6. X LINKED DOMINANT
      1. 1. Fragile X
      2. 2. Aicardi Syndrome
      3. 1. COMMONEST INHERETED CAUSE OF LD {Xq27 (CGG)n}
      4. 1:4000(m), 1:8000(f)
      5. borderline to profound LD
      6. 1. Large testes and ears, typical face, behav like ADHD, Autism, epilepsy~25%
   7. X LINKED RECESSIVE
      1. 1. Hunter's syndrome
      2. 2. Lesch-Nyhan Syndrome
      3. 3. Oculocerebrorenal syndrome of Lowe
      4. 1. Xq27, iduronate sulphatase def.
      5. 1. Profound(type A), mild(type B)
      6. 1. Male Ashkanasi Jews, Dyostosis, eye defects
      7. 2. Mutation in HPRT gene
      8. 2. usually SEVERE
      9. 2. SELF-MUTILATION, Die in early childhood, microcephaly, ~50% have epilepsy
      10. 3. mod to severe LD
      11. 3. 30% have epilepsy, ~70% self-injury
   8. DELETIONS & DUPLICATIONS
      1. 1. Angelmann's (happy puppet) syndrome
      2. 2. Prader- Willi
      3. 3. Crit du chat
      4. 4. Di George(VELOCARDIOFACIAL SYND)
      5. 5. William's synd
      6. 6. Rubenstein taybi synd
      7. 1. Ch 15, microdel, MATERNAL (80%), UPD(2%), direct mutations
      8. 1. SEVERE TO PROFOUND LD
      9. 2. CH 15, microdel, PATERNAL(75%), UPD (25%,maternal)
      10. 2. mild to mod LD, speech AbN
      11. Subtopic 11
      12. 3. SEVERE / PROFOUND
      13. 4. 22q, Microdel
      14. 1. 1:20000 to 1:30000
      15. 2. 1:10000-20000 (m:f = 4:3)
      16. 4. 1:5000
      17. 4. ~50% ld mild to mod
      18. 5. Ch 7, elastin, protein kinase
      19. 5. mild to mod (verbal > motor/visuospatial)
      20. 1. Epilepsy~90%, ataxia, paroxysm of laugher, typical face
      21. 2. Hypogenitalism, over-eating, self-mutilation, speech AbN
      22. 4. Typical face, cardiac AbN(ToF, VSD), seizures~60%
      23. 5. Hypercalcaemia~60%, 'ELFIN' face, wrinkles, sagging skin.
6. NON GENETIC ETIOLOGY
   1. Congenital hypothyroidism
   2. FETAL ALCOHOL SYNDROME
   3. Toxins / hypoxia / infections / dev AbN
7. UNKNOWN ETIOLOGY
   1. RETT'S SYNDROME
   2. Disintegrative disorder
   3. Cornelia de Lange syndrome