Mental Retardation

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

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

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

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.

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

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

Down’s Syndrome

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

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)

Fragile X Syndrome

Fragile X Syndrome

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.

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

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

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.

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

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

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

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

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

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

»» 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