Mental Retardation Definition Mental Retardation is cognitive performance

Mental Retardation

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

Degrees of Impairment (DSMIV) diagnostic &statical manual of mental disorder l Mild MR (IQ of 55 to 70) – applies to about 85% of persons with MR – typically not identified until elementary school years l 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. ) l 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 l 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 21 st 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 l 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) l 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) l Nondysjunction of chromosome 21 l Relative strengths: l – Visual (vs. auditory processing) – Social functioning l Relative weaknesses: – Language expression and pronunciation Generally viewed to suffer less severe psychopathology than other developmentally delayed groups l After 40 years of age, affected individuals nearly always demonstrate postmortem neuronal defects indistinguishable from Alzheimer’s Disease l

Down’s Syndrome

Fragile X Syndrome l l l FMR-1 gene (>200 trinucleotide CGG repeats, Xq 27. 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 l Long face & large floppy ears. l Macrocephaly & Macro-orchidism. l Epilepsy & MR ( moderate , severe) l CT dysplasia ( extensible finger JJ, MVP) l Autism l 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.

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

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

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

PKU Neonatal screening & Dx – Guthrie test 1961 : Blood spot Horst Bickel and Robert Guthrie (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)

Treatment l. A strictly controlled phenylalanine free diet (phenylalanine free formula) l up to the age of about 14 years old l 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

History » 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. .

Examination • • • » 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 « « q DNA analysis: chromosomes q 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 q Imaging : brain MRI , CT , skeleton films q Psychological Assesment: q Electrophysiology : EEG , auditory & visual evoked potentials q

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