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Physician Educa-on in Developmental Disabili-es Webinar
Series Characteris-cs of Neurodevelopmental Disorders;
The Five Essen-al Concepts
Seth M. Keller, MD
July 31, 2012
What are the facts? Sixteen =mes as many people have intellectual disabili=es as have HIV
Intellectual disability is fiHy =mes more prevalent than blindness
Intellectual disability is twenty-‐five =mes more prevalent than deafness
7.7% of the popula=on have neurodevelopmental disorders / intellectual disabili=es (ND/ID)
22 million Americans with ND/ID
With respect to the dispari=es in healthcare;
The medical and dental professions bear some responsibility for the dispari=es in:
-‐ Pa=ent Care
-‐ Teaching
-‐ Research
Results in dispari=es in access and quality of care
Curriculum Assessment of Needs (CAN) Project
How many hours of clinical training in the care of pa=ents with ND/ID do our medical and dental graduates say they actually have upon gradua=on?
Medical Students 81% report 0 hours Dental Students 51% report 0 hours*
*JADA, March 2004 -‐ Wolff A.J.; Waldman H.B.; Milano M.; Perlman S.P.
Concepts needed for the op=mal prac=ce of Developmental Medicine;
The 5 Essen=al Concepts
1. Childhood onset Brain Dysfunc=on can lead to chronic disabili=es
2. Neurodevelopmental Disorder 3. Complica=ons 4. Consequences 5. Syndrome Specific Complica=ons
Why are the Five Essen=al Concepts so important?
There is a widespread lack of a meaningful, scien=fically sound vocabulary or language, rooted in the basic principles of physiology and medicine.
Healthcare providers need a biomedically-‐based conceptual framework, which provides a theore=cal basis for the clinical diagnosis and treatment of pa=ents with neurodevelopmental disorders.
The First Essen=al Concept The major func=ons of the brain require that specific interrelated brain structures work together, in a coordinated fashion. When these rela=onships are improperly developed or disrupted, neurodevelopmental (brain) dysfunc6on will occur. All issues, clinical or otherwise, per=nent to the disability experienced by the individual with neurodevelopmental illness, can be traced directly to this brain dysfunc=on.
The Second Essen=al Concept With the establishment of an accurate diagnosis, the underlying neurodevelopmental disorder responsible for the neurodevelopmental dysfunc=on can be iden=fied.
Neurodevelopmental Disorders Neurodevelopmental disorders can be either gene=c or acquired.
Gene=c causes: Metabolic (PKU) Chromosomal (Trisomy 21, Fragile X) Structural (Spina Bifida, Sturge Weber)
Acquired causes: Prenatal (Fetal Alcohol Syndrome) Perinatal (Hypoxic Injury) Postnatal (Lead Toxicity)
Phenylketonuria Cri-‐du-‐Chat syndrome Homocysteinuria Fragile X syndrome Galactosemia Myotonic dystrophy Lesch-‐Nyhan syndrome Juvenile Huntington’s disease Metachromatic leukodystrophy Tuberous sclerosis San Fillippo syndrome Neurofibromatosis Down syndrome Lissencephaly Trisomy 13 Schizencephaly Trisomy 18 Septo-‐optic dysplasia Klinefelter’s syndrome Sturge Weber syndrome Turner’s syndrome Dandy-‐Walker malformation Arnold-‐Chiari malformation Velo-‐cardio-‐facial syndrome Ring 22 syndrome Agenesis of corpus callosum Angelman syndrome Cornelia de Lange syndrome Prader Willi syndrome Lowe’s syndrome William’s syndrome Lysinuric protein intolerance Smith Magenis syndrome MELAS Rubnstein Taybi syndrome Wilson’s disease
Congenital rubella syndrome Congenital hypothyroidism Toxoplasmosis Toxemia of pregnancy Cytomegalovirus Post-‐natal head injury Herpes Post-‐natal hypoxia HIV Brain tumor Syphilis Post-‐immunization Bacterial meningitis Nutritional disorders Fetal alcohol syndrome Sensory deprivation Cocaine baby syndrome Multiple sclerosis Maternal PKU syndrome Hypoglycemia Placental insufficiency syndrome Childhood suicide attempt Peri-‐natal traumatic brain injury syndrome Surgical complication Kernicterus Severe drug allergy Lead toxicity Pre-‐natal folate deficiency Measles encephalitis Shaken baby syndrome
The Third Essen=al Concept Each neurodevelopmental disorder is associated with one or more primary complica6ons. These complica=ons include:
Cogni-ve impairment (e.g. intellectual disability) Neuromotor dysfunc-on Seizure Psychiatric disorders / abnormal impulsive behavior Sensory Impairment
Complica=ons Cogni-ve Impairment Neuromotor Dysfunc-on*
Intelligence Aeen=on Percep=on Language Visual-‐Spacial Execu=ve Func=on
Hypertonus (Spas=city) Extremity Weakness; low tone
Movement Disorders
*Cerebral Palsy
Complica=ons
Seizures Psychiatric/Behavior
Primary Generalized Focal Seizure Syndrome; Lennox-‐Gaustaut
Au=sm Anxiety/Depression Psycho=c SIB/Aggressive
Visual Hearing Tac=le Olfactory
Sensory
The Fourth Essen=al Concept Depending on which of these five primary complica=ons is present and its severity (some pa=ents manifest all four); the pa=ent suffering from a neurodevelopmental disorder may also demonstrate a number of secondary condi=ons or health
consequences that result from the primary complica=ons.
Cognitive Impairment
Intellectual Disability
Dementia
Special education Reduced $ potential
Access to health care
Poor self esteem
Depression
Reduced chance marriage
No children
Depression/Anxiety
Poor hygiene
Gait dysfunction Trauma
Infections
Neuromotor Dysfunction
Immobility Osteoporosis
Chronic Lung Disease
Scoliosis Aspiration Pneumonia
Fracture
Ca of Esophagus
GERD
Neuromotor Dysfunction
Spasticity
Tremors
Gait dysfunction Falls Trauma
Pain Difficult behavior
Hygiene Infections
Difficulty eating
Difficulty writing
Medicine
Trauma
Seizures
AED complications
Cognitive Fatigue/sedation Dec. ADL’s
Physiologic Organ dysfunction
Psychological Depression/Anxiety
Respiratory failure
Fractures
Osteoporosis Fractures
SIB
Abnormal Behaviors
Anxiety/Depression
Autism
SIB
?????
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Psychopharm.
Aggressive
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Social withdrawal
Limited Communication
Consequences of Abnormal Impulsive Behavior
The FiHh Essen=al Concept In addi=on to the complica=ons and consequences, pa=ents with neurodevelopmental disorders, depending on the precise e=ology, may also demonstrate syndrome-‐specific condi6ons, which may be mul=-‐system in nature, and e=ologically unrelated to the neurodevelopmental (brain) dysfunc=on.
The Six Most Common Diagnoses
Cerebral Palsy Autism Down Syndrome Fragile X Syndrome Fetal Alcohol Syndrome (or Spectrum) Intellectual Disability of Unknown Origin
Cerebral Palsy CP is a disorder of tone, posture or movement due to a lesion in the developing brain; Neuromotor Dysfunc=on
2-‐4/1000; 7-‐10,000 new babies each yr It is sta=c, but it symptoms may change with matura=on
During past 3 decades considerable advances made in obstetric & neonatal care, but unfortunately there has been virtually no change in incident of CP
Cerebral Palsy: E=ologic Prenatal (70%) Infec=on, anoxia, toxic, vascular, Rh disease, gene=c, congenital malforma=on of brain
Natal (5-‐10%) Anoxia, trauma=c delivery, metabolic
Post natal Trauma, infec=on, toxic
Cerebral Palsy: Complica=ons Spas=city Weakness
Increase reflexes Clonus Seizures Ar=cula=on & Swallowing difficulty
Visual compromise Deforma=on
Hip disloca=on Kyphoscoliosis Cons=pa=on Urinary tract infec=on Cogni=ve Impairment
Au=sm Spectrum Disorders Au=sm is a complex, developmental disability that is evident within the first 3 years of life.
It is a behaviorally defined syndrome that is recognized by difficul=es in communica=on, social interac=on and perceptual organiza=on.
Symptoms vary in degree of severity, from mild to severe impairments.
Au=sm Many other disorders have “au=s=c features” and must be excluded:
Sensory deficits IDD Child abuse/neglect Childhood psychoses Neurodegenera=ve diseases Primary communica=on disorders
What Causes Au=sm? It is thought that autism may be associated with a genetic event but no single gene or group of genes account for all autism cases.
Thus, there may be several “autism” genes, potentially representing different ‘profiles’ of autism.
Environmental and dietary factors may also contribute
Incidence Prior to 1990: 4-‐5/10,000 (1/2000 – 1/2500) 1990’s: 21-‐31/10,000 (1/476 – 1/323) A review of 23 epidemiologic studies between 1966 and 1988: 18.7/10,000
Incidence changes to 91/10,000 when Asperger’s syndrome is included
2009: 1/91 to 1/110; M:F ra=o of 4 to 1 556% increase in incidence
Why is the prevalence of ASD increasing?
Changes in diagnos=c criteria-‐-‐broader view of spectrum
Increasing awareness of ASD Recogni=on that ASD can be associated with other disorders
Real increase in the number of individuals with ASD due to factors such as diet, allergies, environmental toxins, vaccines, etc. (Research does not support causal associa=ons with these factors)
Summary of Wing, L. & Potter, D., Mental Retardation and Developmental Disabilities Research Reviews (2002)
by Gail Williams, M.D., Assoc. Professor of Pediatrics, UofL, Weisskopf Center for the Evaluation of Children,
In KATC Newsletter, Issue 8, Winter 2003
CONDITIONS ASSOCIATED WITH AUTISM Condi6on Features Epilepsy Prevalence ranges from 11 to 39 percent
Increased risk in girls and persons with intellectual disability
Gastrointes=nal Primarily diarrhea and cons=pa=on. Associated with day=me behavioral problems
Sleep Disorders Insomnia very common, associated with day=me behavioral problems.
Includes circadian rhythm disturbance and periodic limb movements of sleep
Intellectual disability Prevalence of 41 percent; 30% normal/near normal IQ
Motor impairments Includes hypotonia, apraxia (motor planning), clumsiness, toe walking, gross motor delay
Psychiatric condi=ons High prevalence of anxiety, aeen=on-‐deficit/hyperac=vity disorder, depression
Sensory processing Differences in the percep=ons of sights, sounds, textures, disorder smells, and pain
Down Syndrome Most common and well known gene=c disorder Occurs in about 1/1000 live births in all ethnic groups Nearly all cases occur just once within a given family Only about 2-‐5% of cases run in families Accounts for about 10% of all mentally disabled children
Improved life expectancy mid 50’s but ½ for African American
Incidence In the U.S., approximately 4,000 children are born with Down Syndrome each year
One in every 800 live births Risk increases with maternal age
Age 20 (1/1600) Age 35 (1/350)
Increased risk for second child
Down Syndrome: Cytogene=c Causes
Trisomy: 92% Non-‐disjunc=on results from unequal chromosome division, usually in the mother's egg produc=on
Transloca=on: 3-‐4% the extra chromosome 21 is permanently aeached to another chromosome causing a transloca=on
Mosaicism: 2-‐4% two popula=ons of cells, the trisomy 21 cells, and a second cell line, usually normal
Clinical Features
Brachycephaly Up-‐slan=ng palpebral fissures Epicanthal folds Brushfield spots Flat nasal bridge Folded or dysplas=c ears Open mouth Protruding tongue Short neck Excessive skin at the nape of
neck
Short broad hands Short fiHh finger Incurved fiHh finger Transverse palmer crease Space between first and second
toe
Hyper flexibility of joints
Head and Neck Extremi=es
Special Health Problems Associated With Down Syndrome
Heart defects occur in 30-‐50%
Atlantoaxial Instability
Intes=nal malforma=ons requiring surgery occur in 10-‐12%
Visual and hearing impairments occur in > 50%
Periodontal disease in 90%
Thyroid problems, adult onset leukemia, epilepsy, diabetes,
and Alzheimer's occur more frequently
Intellectual Disability Almost all DS babies have ID Majority have mildly to moderate ID Starts in the first year of life Average age of sixng(11 mon), and walking (26 mon) is twice the typical age
First words at 18 months IQ declines through the first 10 years of age, reaching a plateau in adolescence that con=nues into adulthood
Fragile X Syndrome Leading heritable form of IDD • One in ~260 females and one in ~800 males • are carriers • One-‐third of all X-‐linked IDD
• One in ~4,000 in general popula=on
Leading (known) single gene associated with au=sm • 3-‐6% of all children with au=sm
• Approximately 30% of young children with fragile X syndrome have au=sm
• Is caused by a large CGG-‐repeat expansion in a non-‐coding por=on of the FMR1 gene
Fragile site
Fragile X Syndrome Physical features
• long face/frontal bossing • high arched paleee • large/prominent ears
• macroorchidism
• recurrent O==s Media; Conduc=ve hearing loss
• aor=c dilata=on with mitral valve prolapse
• patellar disloca=ons/joint laxity • premature menopause
Expression of the FMR1 gene Normal Premutation Full mutation
(CGG) n < 55 55 ≥ n ≤ 200 (CGG) n ≥ 200 (CGG)
Normal Emotional problems Fragile X syndrome Premature ovarian failure FXTAS
gene
mRNA
FMRP
Clinical phenotype
transcription
translation
Fetal Alcohol Spectrum Disorders
FAS -‐-‐the most severe diagnosis on the spectrum of alcohol related disorders
FASD -‐-‐Fetal Alcohol Spectrum Disorder ARBD (alcohol related birth defects) ARND (alcohol related neuro-‐developmental disorder)
FAE (fetal alcohol effects) FAS (fetal alcohol syndrome)
FAS Facts
• The leading cause of acquired and preventable IDD • Dose-‐response effect-‐-‐-‐the more alcohol the higher the likelihood of FAS • No known safe level of alcohol use during pregnancy
Criteria for FAS Diagnosis A diagnosis requires the presence of all three of the following: Documenta=on of three facial abnormali=es
smooth philtrum thin vermillion border small palpebral fissures
Documenta=on of growth deficits Documenta=on of CNS abnormali=es
CNS Abnormali=es
• Memory problems • Aeachment disorder • Impaired motor skills • Learning disabili=es • Problems with reasoning and judgment • Inability to discern consequences of ac=ons • Intellectual impairment
Neurodevelopmental Disorders
ID of Unknown Origin S=ll very common, but with selec=ve workup and history may be able to determine cause in majority of cases
Understand ra=onale to find underlying cause; An=cipatory Guidance
Syndromic vs non-‐Syndromic; Phenotype Family History
Medical chart review May guide family’s reproduc=ve health
Neuromotor Dysfunction
ND Disorder
Cognitive Impairment
Seizures
Abnormal Behaviors
Genetics Nutrition
Trauma Toxins
Complications
Complications
Complications
Complications
Complications
Complications
Complications
Complications Syndrome Specific Conditions
Sensory Impairment
Remember what the Five Essen=al Concepts tell us . . . 1. There’s a problem with the brain (brain dysfunc=on) 2. There’s an underlying neurodevelopmental disorder involved
3. The disorder will manifest classic symptom complexes / complica=ons
4. There will be secondary health consequences associated with those complica=ons
5. There will also be syndrome-‐specific condi=ons, unrelated to brain dysfunc=on
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