1. Mental Retardation

2. Definition
Mental Retardation is cognitive performance that is two standard deviation below the mean of the general population (below the 3rd percentile )
Deficits in IQ and adaptive functioning
IQ of 70 or below

3. Degrees of Impairment (DSM-IV) diagnostic &statical manual of mental disorder
Mild MR (IQ of 55 to 70)
applies to about 85% of persons with MR
typically not identified until elementary school years
Moderate MR (IQ of 40 to 54)
applies to about 10% of persons with MR
usually identified during preschool years
applies to many people with Down syndrome

4. Degrees of Impairment (cont.)
Severe MR (IQ of 20 to 39)
applies to about 3%-4% of persons with MR
often associated with organic causes
usually identified at a very young age
Profound MR (IQ below 20 or 25)
applies to about 1%-2% of persons with MR
usually identified in infancy
almost always associated with organic causes and often co-occurs with severe medical conditions

5. Causes of Mental Retardation
Genetics:
chromosomal abnormalities are the most common cause of severe MR
Down syndrome due to an additional 21st chromosome
Prader-Willi and Angelman syndromes both associated with abnormality of chromosome 15
Non chromosomal abnormalities:
AR,PKU
AD , Neurocutanous disoders like Neurofibromotosis, TS.
Fragile X syndrome.

6. Causes of Mental Retardation
Environmental
Neurobiological influences
adverse biological conditions (e.g., malnutrition, exposure to toxins, prenatal and perinatal stressors)
infections, traumas, and accidental poisonings during infancy and childhood
prenatal alcohol exposure can lead to a Fetal Alcohol Spectrum Disorder (FASD)
Social and Psychological influences
deprivation of physical and emotional care and social stimulation particularly influential

7. Down’s Syndrome
Most common chromosomal abnormality leading to MR (1.2/1000 births)
Nondysjunction of chromosome 21
Relative strengths:
Visual (vs. auditory processing)
Social functioning
Relative weaknesses:
Language expression and pronunciation
Generally viewed to suffer less severe psychopathology than other developmentally delayed groups
After 40 years of age, affected individuals nearly always demonstrate postmortem neuronal defects indistinguishable from Alzheimer’s Disease

8. Down’s Syndrome

9. Fragile X Syndrome
FMR-1 gene (>200 trinucleotide CGG repeats, Xq27.3)
An example of a “dynamic mutation” where more mutations occur with successive generations
General problems: MR, mild CT dysplasia, & macro-orchidism
Only 50% of females with the full mutation demonstrate IQs in the borderline/mild MR range (vs. 100% of males)
Increases the risk for ADHD, autism (20-60%) & social phobia
Increasing deficits in adaptive and cognitive functioning with age

10. CF Long face & large floppy ears. Macrocephaly & Macro-orchidism.
Epilepsy & MR ( moderate ,severe)
CT dysplasia ( extensible finger JJ, MVP)
Autism
DX: Cytogenetic analysis.(for repeats)

11. Fragile X Syndrome

12. Fragile X Syndrome

13. Phenylketonuria Genotype:
AR disease due to Mutation of the enzyme, phenylalanine hydroxylase (PAH) that hydroxylate phenylalanine to Tyrosine.
Phenotype:
Mental Retardation, Seizures, Fair Skin, “Mousy Odor” & Eczema.

14. PHENYLALANINE HYDROXYLASE
The normal metabolism of phenylalanine
(pathways a and b)
BREAKDOWN
Dietry sources, particularly plant proteins
PHENYLALANINE HYDROXYLASE
PHENYLALANINE
TYROSINE
(b)
(a)
BODY PROTEINS
© 2008 Paul Billiet ODWS

15. PHENYLALANINE HYDROXYLASE
The abnormal metabolism in phenylketonuric subjects
(pathway c)
HYDROXYPHENYLACETIC ACID
HYDROXYPHENYLACETIC ACID*
(c)
PHENYLALANINE*
Dietry sources, particularly plant proteins
BODY PROTEINS
(b)
(a)
PHENYLALANINE HYDROXYLASE
(c)
PHENYLACETIC ACID (Brain)*
*Agents, thought to be responsible for mental retardation
© 2008 Paul Billiet ODWS

16. Symptoms of PKU Normal at birth At 2 month (Vomiting, lethargy)
Light hair, eyes, and skin
Eczema-like rash
Seizures (Hypsarrythmia)
Hyperactivity
Hypertonia and hyper-reflexia.
Unpleasant musty/ mousy body odor
Mental retardation & microcephaly.

17. PKU Neonatal screening & Dx
Guthrie test 1961 : Blood spot (filter paper) samples using the Guthrie bacterial inhibition assay
Urine ferric chloride test (Ferric chloride + urine of new born baby Green colour in the presence of ketone bodies)
Horst Bickel and Robert Guthrie

18. Treatment A strictly controlled phenylalanine
free diet (phenylalanine free formula)
up to the age of about 14 years old
After this age the growth and development of the brain is not affected by high levels of phenylalanine in the body
© 2008 Paul Billiet ODWS

19. »complete and detailed history«
complete systemic review
pregnancy history : maternal age , parity , infections..
birth : type , wt . GA ,complications , apgar score
Postnatal : incubator , ventilator , disease ..

20. History (cont.) developmental Hx : mile stones , speech ..
educational Hx : schooling , IQ tests
behavioral Hx : skills , attention , activity
family Hx : consanguinity , inherited ds ..

21. »complete and detailed examination«
Growth parameters :
Dysmorphic features :
CNS examination :
Other system and skin exam :
IQ tests :
Developmental testing :

22. Investigations
»» there is no specific investigation for MR but good hx and physical examination guide us toward the proper one ««
DNA analysis: chromosomes
FISH probes: Prader-willi,wiliams,cri du chat syndrom (Fluorescence in situ hybridization (FISH) is a molecular diagnostic technique utilizing labeled DNA probes to detect or confirm gene or chromosome abnormalities.) 
Metabolic labs:plasma a.a. , urine organic a. ,TFT , ck
Imaging : brain MRI , CT , skeleton films
Psychological Assesment:
Electrophysiology : EEG , auditory & visual evoked potentials

23. »» there is no specific Rx for MR ««
Management of MR
»» there is no specific Rx for MR ««
»General rules :
-Identify the cause then initiate a comprehensive plan
-Special educator , Language , behavioral and occupational therapists
-Special school programs
-Community services