ADHD and Mental Retardation

ADHD and Mental Retardation
By:Daniel M. Bagner, M.S.

Mental Retardation
* Sub average intelligence (IQ < 70: DSM-IV; <75: AAMR)
* Associated adaptive deficits in at least two areas:
o Communication, self-care, home living, social skills, community use, self-direction, health and safety, functional academics, leisure, and work
* Occurrence of deficits before age 18
Classification of MR
Pervasive Profound/custodial
Extensive
Severe/trainable
Intermittent
Educable
Mild
IQ range
Support required
Educational Classification
Level of MR
Etiology of MR
ADHD in MR
ADHD in Genetic Etiologies of MR

* Down Syndrome
* Fragile X syndrome

Underdiagnosis of ADHD in MR
* Symptoms less obvious than other disorders such as psychosis (Fisher, Burd, Kuna, & Berg, 1985)
* “Diagnostic overshadowing” (Reiss, Levitan, & Szyszko, 1982)

Developmental Appropriateness of ADHD in Children With MR
* DSM-IV suggests taking child’s mental age (MA) into account for assessing hyperactivity
* For rating scales
* Interdiagnoser reliability difficult when accounting for a child’s cognitive development

Developmental Appropriateness of ADHD in Children with MR
* If DSM-IV guidelines are correct
* Pearson and Aman (1994)
* Not necessary to adjust for IQ or MA but may be appropriate to control for CA
* Parents and teachers may make implicit corrections

Prevalence of ADHD in MR
Sustained Attention in MR
Selective Attention in MR
Attention in MR and ADHD in the Classroom
Similarities of ADHD: With or Without MR
“Breadth of Attention” in MR
Impulsivity in MR
Hyperactivity in MR
Hyperactivity in ADHD and MR in the Classroom
Aggression in MR and ADHD
Behavioral Adjustment in Children with MR and ADHD
Risk Factors in Children with ADHD and MR
Long-term Prognosis
Characteristic of and often observed in children with MR
Medication for ADHD in Children with MR
Behavioral Treatments for ADHD in Children with MR
Future Directions

ADHD and Mental Retardation.ppt

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Genetic Diseases

Genetic Diseases
Presentation by:Amrik Sahota
Dept Path & Lab Med
UMDNJ - RWJMS

What’s the Nature of This Talk?

* Review
* Preview
* Overview

Major Topics
* Mutations
* Single gene disorders
* Chromosomal disorders
* Multifactorial disorders
* Molecular diagnostics
* Pediatric disorders (not discussed)

DNA RFLPs
HLA antigens
Serum proteins
Blood groups
Structural changes
Chromosomes
Marker
Polymorphic Markers
Microsatellite markers
Single Nucleotide Polymorphisms
Causes of Mutation
* Spontaneous mutations
o Arise naturally during DNA replication
* Induced mutations
o Ionizing radiation (X-rays)
o Non-ionizing radiation (UV)
o Chemical mutagens

Types of Mutation
* Single gene mutations
o Minor structural alterations (single base changes, deletions, insertions, etc)
* Chromosomal mutations
o Major structural alterations (deletions, insertions, inversions, translocations, etc)
o Loss or gain of whole chromosomes (monosomies, trisomies, etc)

Single Gene Mutations
* Structural gene mutations
* Regulatory region mutations
* Dynamic mutations

Point Mutation (Sickle Cell)
Single Base Deletion (ABO)
Three-base Deletion (Cystic Fibrosis)
Premature Chain Termination (Beta Thalassemia)
Four-base Insertion in Hexosaminidase A Gene (Tay-Sachs)
Summary of Single Gene Mutations
Type Effect Example
Deletion Null Cystic fibrosis
Insertion Null Tay-Sachs
Inversion Null Hemophilia A
Missense Null Sickle cell
Nonsense Null Beta-globin
Frameshift Null Cystic fibrosis
Splicing Null Beta-globin
Regulatory Low exp. Beta-globin

Molecular Consequences of Single Gene Mutations
* Loss of function
* Haploinsufficiency
* Dominant negative mutation
* Gain of function

Loss of Function Mutations
Adenine Phosphoribosyltransferase (APRT) Deficiency
Adenine
DHA
Crystals in kidney
Stones in kidney
Renal injury
XDH
Precipitation/crystallization
Aggregation
Blockage of tubules
Tubular loss
Renal failure
AMP
APRT
T Insertion
Recognition Sequence by Tru9I
TCT Deletion
Recognition Sequence by Mbo II
E5-wild:
E5-mutant:
APRT Mutations
Haploinsufficiency
FH and LDL receptor
LDL Receptor Mutations
Dominant-negative Mutations
Dominant-negative Mutations: Collagen Genes
Gain of Function Mutation
Gain of Function Mutation: Oncogenes
Chromosomal Mutations
* Deletion: Loss of a piece of a chromosome
* Translocation: Breakage of two chromosomes and fusion of broken parts
* Isochromosome: Loss of one arm and duplication of the other
* Aneuploidy: Gain or loss of one or more intact chromosomes
* Mosaicism: More than one chromosomal complement in a given individual
Normal Male Karyotype
Types of Genetic Disorders

* Single gene disorders
* Chromosomal disorders
* Multifactorial disorders

Single Gene Disorders
* Thalassemia 1/50
* HNPCC 1/200 to 1/1000
* Sickle cell 1/400 to 1/600
* Cystic fibrosis 1/2,000 to 1/4,000
* Marfan syndrome 1/10,000 to 1/20,000

Inheritance Patterns For Single Gene Disorders

* Classic
* Non-classic
Autosomal Dominant Inheritance
Autosomal Recessive Inheritance
X-linked Inheritance
Mitochondrial Disorders
Mitochondrial Inheritance
Mitochondrial Inheritance (Leber Optic Neuropathy)
Other Disorders
Fragile X Syndrome
Fragile X Chromosome
Fragile X Pedigree
Nucleotide Repeat Mutations
Pathology of Single Gene Disorders
Sickle Cell Mutation
Normal and Sickle Cell Hemoglobin
Sickle cell
ORGAN/TISSUE INVOLVED
PROBLEMS CAUSED
KIDNEY
Hematuria
Urinary frequency
SPLEEN
Serious infections
Abdominal pain
LUNGS
Pneumonia
Chest problems
BONES
Infection Necrosis
BRAIN
Stroke
Headache
LIVER
Hepatomegaly
Jaundice
Complications of Sickle Cell Disease
NCBI
Chromosomal Disorders
Normal Male Karyotype
X Chromosome Idiogram
Finding Our Way Around
Sub-sub-band (q11.11)
Common Multifactorial Disorders
Frequency of Multifactorial Disorders
Multifactorial Versus Single Gene Disorders
Comparison of Single Gene and Multifactorial Diseases
Multifactorial Versus Polygenic Diseases
Interactions Between Genes and Environment
Molecular Diagnostics
Direct Gene Diagnosis (Factor V)
Allele Specific Oligo Probes
Fragile X Analysis
Summary

* Mutations
* Single gene disorders
* Chromosomal disorders
* Multifactorial disorders
* Molecular diagnostics

Genetic Disorders: Here and Now
Era of Genetic Medicine

Genetic Diseases.ppt

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Variations in Chromosome Number and Arrangement

Variations in Chromosome Number and Arrangement

* Chromosomal mutations or aberrations
o Abnormal chromosomal number
o Gene deletion or duplication
o Chromosome rearrangements
* Aberrant chromosomes passed on in a Mendelian fashion

Terminology
* Euploid – chromosomes present in complete haploid units
o Haploid
o Diploid
o Triploid
o Tetraploid
* Aneuploid – loss or gain of one or more chromosomes
* Alloploid – multiples of different genomes

Aneuploidy
* Commonly results from nondisjunction during meiosis
o Monosomy, trisomy, tetrasomy, etc.
o Klinefelter and Turner syndromes are examples involving human sex chromosomes

Nondisjunction
Monosomy
Cri-du-Chat Syndrome
* Autosomal monosomy in humans not reported beyond birth (die quickly)
* Partial autosomal monosomy may survive
* “Cry of cat” syndrome

Trisomy
* Trisomy (2n + 1)
* Meiotic issues

Trisomy Meiosis
Down Syndrome
* Discovered in 1866 by John Langdon Down
* Now known to result from trisomy 21 (47 +21)
* One per 800 live births
* 75% due to nondisjunction in meiosis I
* Ovum is source of extra 21 in 95% of cases

Down Syndrome – Trisomy 21
Maternal Age and Down Syndrome
Patau Syndrome
Edwards Syndrome
Viability in Human Aneuploidy
More From the Carr Study
Polyploidy in Plants
Autopolyploidy
Experimentally Produced Tetraploids
Yeast Models
Allopolyploidy
Allotetraploid Formation
Allotetraploids
Wheat/Rye Cross
Somatic Cell Hybridization
Protoplast Fusions
Endopolyploidy
Chromosome Rearrangements
Consequences of Rearrangements
Deletions
Compensation Loop in a Polytene Chromosome
Duplications
Unequal Crossing Over
Position Effects
Gene Duplication and Evolution
Chromosomal Inversions
Inversions and Gametogenesis
Inversions and Recombination
Translocations
Familial Down Syndrome
Fragile Sites
Fragile X Syndrome
Fragile X Chromosomes

Variations in Chromosome Number and Arrangement.ppt

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