Genetic Disorders and Intellectual and Developmental Disabilities

1
Genetic Disorders and Intellectual and
Developmental Disabilities

• Terrence McNelis, MPA
• Tmcnelishome_at_comcast.net

2
History of Genetics cont

• Genome Project
• Largest Scientific Endeavor- 25 Countries/18
  Years
• Mapping of Human Genes
• 23 Set of Chromosomes
• 31,000 Genes
• 1995 - 285 causes of Intellectual Disability
• 2007 - 1200 Genetic Causes of Intellectual
  Disability

3
Description versus Etiology

• Allows Genetic Counseling
• Anticipates Medical Needs
• Allows Insight
• Vulnerabilities
• Behaviors
• Learning Styles
• Life Span Approach
• Support Groups

4
Syndromic Approach

• Biological Basis
• Synthesizing Concept
• Medical Profiles
• Aging Sequence
• Behavioral Profiles
• Assists in Deciphering Behaviors
• Behavioral Phenotype- may or may not Constitute
  Psychiatric Disorder

5
Beware of Generalizations

• There are very important variations in genetic
  syndromes. They are
• Medical
• Physical
• Cognitive
• Behavioral

6
Pitfalls of Syndrome/Etiological Approach

• Accepting Behavior as a forgone conclusion
• Additional Stigmatization
• Inadvertent Reinforcement of Behaviors
• Ignoring Differences within a Syndrome

7
Design of DSM IV

• Axis I Clinical Syndromes
• Axis II Personality Disorders
  Mental Retardation
• Axis III General Medical Conditions
• Axis IV Psychosocial and
  Environmental Issues
• Axis V Global Assessment of
  Functioning

8
Mental RetardationTwo Standard Deviations From
Mean

• Code based on degree of severity reflecting level
  of intellectual impairment
• 317 Mild Mental Retardation
• IQ level 5055 to approximately 70
• 318.0 Moderate Mental Retardation
• IQ level 3540 to 5055
• 318.1 Severe Mental Retardation
• IQ level 2025 to 3540
• 318.2 Profound Mental Retardation
• IQ level below 20 or 25

9
Descriptive Definition of Mental Retardation

• Two Standard Deviations from the mean (Average
  IQ)
• Two areas of skill deficit
• (ADL, Communication, Self Care etc)

10
Genetic Syndromes

• Down Syndrome
• Most Common Well Known
• Fragile X Syndrome
• Most Inherited Form of MR
• Smith-Magenis Syndrome
• Believed Rare
• Lesch- Nyhan
• Extremely Rare

11
Genotype Phenotype

• Phenotype Observable Manifestations of the
  underlying Genotype-
• Genotype Persons genetic makeup

12
Down Syndrome

• 1/800 births worldwide, 1/1600 US
• Trisomy 21, extra chromosome 21
• 92 Trisomy 21
• 3-5 Mosaic
• 3-5 Robertsonian Translocation (Transmittable)
• Prevalence
• Significant Increase gt 45 years old (132)
• 80 Moms lt 35 years old.

13
Down SyndromePhysical Characteristics

• Microcephaly and abnormally shaped head
• Prominent facial features
• Flattened nose, protruding tongue,upward slanting
  eyes with rounded inner eye fold
• Broad short hands, short fingers, with single
  palm crease
• Short stature

14
Down Syndrome -Health Issues

• Congenital Heart Problems 50
• Hearing Loss 66-89
• Opthamic (Strabismus) 60
• Hypothyroid 50-90
• Periodontal Crowding 60-100
• Subluxation of Spine 15
• Obesity 50-60
• Seizure Disorder 6-15
• Sleep Disorder 10-20
• Frequent Respiratory Infections

15
Down Syndrome- Psychological Issues

• Average mental age of 8 years
• Mild to severe mental retardation
• Less psychopathology than mixed etiology
• Depression - 6 -10 Unipolar, apathy, withdrawal
• Bipolar and Mania is rare

16
Down Syndrome

• Seizures in Older Persons with Down Syndrome
• ADHD General Population
• Autistic Disorders Appear More Frequently
• Self Talk is Common

17
Down Syndrome- Alzheimers

• gt30 Years many brains show Alzheimers Plaque and
  Tangles
• 15-40 Show Behavioral Symptoms of Alzheimers
  (maybe over diagnosed)
• Two genes on the 21st Chromosome implicated in
  Plaque and Tangles
• Development rate slows with age

18
Down Syndrome Strengths

• High Visual Memory
• Sequential Processing Intact
• Language reception excellent (20 years)
• Good at Breaking down tasks
• High social ability
• Increased Life Expectancy 75

19
Down Syndrome Vulnerabilities

• Expressive Language
• Articulation and Grammar
• Hearing Impairment and Oral Structure
• Prevalence of Medical Problems
• Accelerated Aging Process

20
Implications To Care Givers

• Medical Interdiction is well known
• Sequential v Gestalt Learners
• Psychiatric Predictions
• Medical Causes of Behavior
• Aging Process

21
Fragile X Syndrome

• Most common inherited cause of mental retardation
• Prevalence 1 in 2000 males
• 1in 4000 Females
• 1 in 259 Women carry Fragile X
• 1 in 800 Men
• Trinucleotide expansion (repeated sequence)
  within the FMR1 gene on the X Chromosome
• 80-90 not yet correctly Diagnosed

22
Fragile X Syndrome

• Expanded Repetition of Trinucleotide CCG
• Normal 6-50 repeats
• Premutation 50-200 Repeat (FXTAS)
• Full Mutation 200 Fragile X

23
FXTAS Fragile X associated Tremor/Ataxia
Syndrome

• Progressive Neurological Disorder
• Onset 50 60 yrs (Granddads of Fragile X Kids)
• Only 20-30 of Male carriers gt50 yrs affected
• Often Misdiagnosed as atypical Parkinsons or
  Multiple System Atrophy

24
Fragile X Syndrome- Physical Characteristics

• Macrocephaly (Large Head)
• Long, Narrow Face
• Can have prominent ears and hyper-extensible
  finger joints
• As boys move to puberty, macroorchidism develops
• Low Muscle Tone
• Mitral-valve Prolapse (echo cardiogram)

25
Fragile X Syndrome

• Parent are often Unaware of diagnosis until 18 to
  24 months of age.
• Misdiagnosed as PDD-NOS
• Linguistic Delays
• Hand Flapping
• Hand Biting
• Gaze Aversion
• Resistance to Change

26
Fragile X Syndrome

• Broad range of symptoms
• Shyness, Excessive social anxiety and learning
  problems
• Difficulty w Peer interactions
• Mental retardation (95 have mild or moderate MR)
• 70 females have cognitive deficits in addition
  to emotional problemsmood labile, ADHD
• 85 males have MR or autistic like features such
  as poor eye contact (gaze aversion), hand
  flapping tactile defensiveness

27
Fragile X Syndrome Vulnerabilities

• Hyper/Hypo Arousal (sound of fluorescent lights,
  too many Decorations, Familiar voices)
• Reject eye contact
• Poor auditory processing
• Sensory Integrative disorder (including motor
  planning and fine motor)
• Deficiency in sequential processing
• Transitions and Change (Due to above)
• Highly anxious
• Tactile Defensiveness

28
Tactile Defensiveness

• 60 -90 0f Boys, some Girls
• Touch, Clothing, Tags
• Deep Pressure vs Light
• End of Line
• Infants not comforted by cuddling
• Hygiene, Dental related to TD

29
Fragile X Syndrome Strengths

• Ability to do simultaneous activity
• Imitation and modeling (good and bad)
• Although shy, friendly
• Good sense of humor
• excellent long term memory
• responds well to structure

30
Implications to Care Givers

• Prevalence Toward Anxiety
• High Cathedral Mouth/ Stuffing
• Sensory Diet Textures
• Neuro developmental Therpy
• Depression/ Bipolar in addition to Anxiety
• Learning Style
• Gestalt
• Multi Tasking
• Visual vs Auditory
• 80 90 Not Diagnosed

31
Smith-Magenis Syndrome

• Deletion of chromosome 17 (17p11.2)
• deletion occurs randomly around conception
• 1 in 25,000 births (considered rare)
• Described in 1980
• Generally underdiagnosed but has distinct and
  recognizable patterns of physical, behavioral and
  developmental features

32
Smith-Magenis Syndrome- Physical Characteristics

• Short stature
• Characteristic facial appearance flattened
  mid-face, down-turned mouth, prominent and often
  rosy cheeks
• Prominent jaw in older children and adults
• Chronic ear infections
• Hearing impairment

33
Smith-Magenis Syndrome Physical Characteristics

• Eye problems (strabismus and myopia)
• Hoarse voice
• Short fingers and toes
• Heart defects
• Problems related to urinary system
• Often Retinal Detachment

34
Smith-Magenis Syndrome- Vulnerabilities

• Self Injurious Behavior
• Hand Biting
• Head Banging
• Picking at finger and toes (nails)
• Skin picking
• Insertion of objects
• Auto-amplexation

35
Smith-Magenis Syndrome- Vulnerabilities continued

• Severe tantrums
• Sleep disturbances
• Frequent awakening
• Early Rising
• Narcolepsy
• Reversal of normal meletonin
• deletion on gene for cicadian rhythm

36
Smith-Magenis Syndrome Strengths

• Engaging
• Appreciation of Attention
• Eager to please
• Sense of humor
• good verbal communication

37
Smith-Magenis Syndrome Strategies

• Get to antecendents
• Transition
• End of pleasurable activity
• Changes
• Emotional upset in staff or others
• Remove from area to reduce reinforcement
• Calm response, behaviors are internally driven

38
Lesch-Nyhan Syndrome

• 1 of 100,000 Births
• Mutation of the HPRT Gene on the X Chromosome
• Rarely in Females
• Sequellae
• Deficiency of Enzyme HPRT, causing over
  production of Uric Acid
• Neurological Disability and Behavioral Problems
• (NINDS, 2009)

39
Symptoms

• Usually first appearance around 3 to 6 months
  orange sand in diapers
• 6 -18 months involuntary movements
• Hypotonia
• By age 4 Self Mutilation
• Growth Retardation, testicular atrophy, puberty
  delayed or absence
• Possible degenerative Joint disease
• (NINDS, 2009)

40
Characteristics

• Over production of uric acid causes marked
  Inflammation and Arthritis
• Mild to Moderate ID
• Compulsive Behaviors always including SIB
• Hitting
• Spitting
• Copropraxia
• (NINDS, 2009)

41
Self Injurious Behavior

• Biting Tongue and Cheek
• Head, Arm and Leg Banging
• Nose and Eye Gouging
• Possible loss of Lips, fingers, vision
• Spasticity and Choreoathetosis
• Wheelchair Bound
• Kicking, Head Butting, Sexual Touching, vomiting
  then apologizing
• (NINDS, 2009)

42
Treatments

• Allopurinol to reduce Uric Acid
• Some use of phenobarbitrol and halperidol
• Use of Protective Devices
• Use of Restraining Devices
• Selective Ignoring
• Benzodiazepines may reduce anxiety
• Deep Basal Ganglia Stimulation
• (NINDS, 2009)

43
Implications of Genetics

• Ability to Predict Physical Issues
• Some Future Handle on Behavioral Issues
• Insight into New Methods of Communication and
  Learning

44
Syndrome Information

• www.NDSS.org
• www.smithmagenis.org
• www.fraxa.org
• www.ninds.nih.gov/disorders/lesch_nyhan