Intellectual Disability

Intellectual Disability
Intellectual Disability = significantly sub-average intellectual functioning with related limitations in 2< adaptive skills

Adaptive Skills = communication; self-care; home living; social skills; leisure; community use; self-direction; health and safety; functional academics; work

Formal IQ testing not possible until 5 years of age Autism Spectrum Disorder/Pervasive Developmental Delay = broad spectrum of disease which includes deficiencies in three areas
 * Incidence = 1.14% of school age children, 1.8/1000 males, 30% more Males than Females
 * Identified Cause = 50%
 * Social Interaction
 * Communication
 * Restrictive, repetitive & stereotypic patterns of behavior, interests, or activities

Molecular Etiology of Intellectual Disability

 * 10-12% X-Linked Intellectual Disability
 * 12% Down Syndrome
 * 5% Chromosome Structure
 * >2% Subtelomeric
 * 15% Pathogenic CNVs
 * 3% Fragile X
 * 1.4% 16p13.11 deletion
 * 1% Inborn Errors of Metabolism
 * Also: AR, AD Disorders, Environmental Exposures
 * Unknown

X-Linked Intellectual Disability

 * 153 syndromes, 90+ genes
 * Syndromic vs. Nonsyndromic (1:2)
 * Molecular Mechanisms
 * Rho/Rab GTPase signaling pathways = involved in neuronal differentiation, synaptic plasticity
 * Regulation of gene expression
 * Other processes = cell adhesion, transcription regulation, posttranslational modification, signal transduction, ubiquination, actin cytoskeleton modification, sodium transport

Intellectual Disability Evaluation

 * Benefits of Evaluation
 * identification of appropriate medical and nonmedical therapies
 * identification of indicated medical intervention/referrals
 * presymptomatic screening for associated complications/functional disabilities
 * educational planning
 * elimination of unnecessary testing and evaluations
 * anticipatory guidance
 * education and advocacy
 * referral to appropriate medical/social services
 * reproductive counseling, carrier testing, prenatal diagnosis
 * family networking
 * Approach to Evaluation
 * Medical History
 * prenatal, birth history, birth stats
 * neonatal period, hospitalizations
 * developmental history = attainment of milestones, progression vs regression
 * growth history
 * review of systems
 * behavior patterns
 * Family History
 * 3 Generation Pedigree
 * Sweep Questions = ID? Learning Disabilities? Psychiatric problems?
 * Family Resemblance
 * Physical Exam
 * growth parameters
 * skin findings (with Woods lamp)
 * minor anomalies
 * measurements
 * facial features
 * What is the most unusual feature?
 * head size - congenital or progressive?
 * Neurological Exam
 * weakness
 * muscle tone
 * extrapyramidal signs = hyperreflexia, gait, movements
 * cerebellar signs = ataxia
 * behavior
 * Acute Neurological Changes
 * aminoacidopathies
 * organic acidurias
 * energy production disorders
 * lysosomal storage disorders
 * peroxisomal disorders
 * Loss of skills/Regression/Plateauing
 * All of the Above
 * Rett Syndrome
 * Lesch-Nyhan Syndrome
 * Review of Medical Records, Photographs
 * Testing
 * audiology (always rule out hearing loss)
 * ophthalmology
 * psychometric assessment
 * X-rays
 * Neuroimaging
 * High frequency of brain abnormalities with ID
 * CT best for craniosynostosis, intracranial calcifications
 * Useful for: macrocephaly, microcephaly, seizures, loss of psychomotor skills, spasticity
 * Metabolic Testing Indications
 * FTT
 * Recurrent illness
 * Seizures
 * Ataxia
 * Hypotonia
 * Coarse Features
 * Eye abnormalities
 * Recurrent coma/lethargy
 * Metabolic Acidosis
 * Abnormal Sexual Differentiation
 * Hepatosplenomegaly
 * Hyperuricemia
 * Hyperammonemia
 * Low cholesterol
 * Structural hair abnormalities
 * Unexplained deafness
 * Bone abnormalities
 * dysostosis, occipital horns, punctate calcifications
 * Skin abnormalities
 * angiokeratoma, ichthyosis
 * Test of Time = Diagnoses Increase 5-20% with return visits; phenotypic evolution

Syndromes/Conditions Associated With Intellectual Disability

 * Trisomy 21 = Avg IQ ~50
 * Trisomy 18 = Severe
 * Trisomy 13
 * 47, XXX = Mild, IQ ~85-90
 * Mosaic Trisomy 8 (Warkany Syndrome) = IQ ~40-75, to normal
 * Mosaic Trisomy 9 = Severe
 * Tetrasomy 12p = Profound
 * Ring X Syndrome
 * Cat-Eye Syndrome = Borderline
 * Deletion 4p- (Wolf Hirschhorn Syndrome) = Severe
 * Deletion 5p- (Cri-du-Chat Syndrome) = Moderate - Severe
 * WAGR
 * Williams Syndrome = Mild - Moderate; exceptional verbal ability
 * Miller-Dieker Syndrome = Profound
 * Cornelia de Lange Syndrome = IQ <30-100, average 53
 * Angelman Syndrome
 * Coffin-Lowry Syndrome
 * ARX Gene & Associated Syndromes
 * Fragile X
 * Bardet-Biedel
 * Hypomelanosis of Ito
 * Smith-Magenis Syndrome
 * Rett Syndrome
 * Lesch-Nyhan Syndrome
 * Homocystinuria
 * Tuberous Sclerosis
 * Smith-Lemli-Opitz
 * Kabuki Syndrome
 * Menke's Disease