RELATED DISORDERS ADHD ADHD DSM-IV Criteria I. Either A or B: A. Inattention: Inattention 1. Often does not give close attention to details or makes careless mistakes in schoolwork, work, or other activities. 2. Often has trouble keeping attention on tasks or play activities. 3. Often does not seem to listen when spoken to directly. 4. Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (not due to oppositional behavior or failure to understand instructions). 5. Often has trouble organizing activities. 6. Often avoids, dislikes, or doesn't want to do things that take a lot of mental effort for a long period of time (such as schoolwork or homework). 7. Often loses things needed for tasks and activities (e.g. toys, school assignments, pencils, books, or tools). 8. Is often easily distracted by extraneous stimuli. 9. Is often forgetful in daily activities. 1
ADHD DSM-IV Criteria, continued B. Hyperactivity-Impulsivity: Six (or more) of the following symptoms of hyperactivity-impulsivity have been present for at least 6 months to an extent that is maladaptive inconsistent with developmental level: Hyperactivity 1. Often fidgets with hands or feet or squirms in seat when sitting still is expected 2. Often gets up from seat when remaining in seat is expected. 3. Often excessively runs about or climbs when and where it is not appropriate (adolescents or adults may feel very restless). 4. Often has trouble playing or doing leisure activities quietly. 5. Is often "on the go" or often acts as if "driven by a motor". 6. Often talks excessively. ADHD DSM-IV Criteria, continued Impulsivity 7. Often blurts out answers before questions have been finished. 8. Often has trouble waiting one's turn. 9. Often interrupts or intrudes on others (e.g., butts into conversations or games). ADHD DSM-IV Criteria, continued II. Some hyperactive-impulsive or inattentive symptoms that cause impairment were present before age 7 years. III. Some impairment from the symptoms is present in two or more settings (e.g. at school/work and at home). IV. There must be clear evidence of clinically significant impairment in social, school, or work functioning. V. The symptoms do not happen only during the course of a Pervasive Developmental Disorder, Schizophrenia, or other Psychotic Disorder. The symptoms are not better accounted for by another mental disorder (e.g. Mood Disorder, Anxiety Disorder, Dissociative Disorder, or a Personality Disorder). 2
ADHD DSM-IV Criteria, continued Based on these criteria, three types of ADHD are identified: IA. ADHD, Combined Type: if both criteria IA and IB are met for the past 6 months IB. ADHD, Predominantly Inattentive Type: if criterion IA is met but criterion IB is not met for the past six months IC. ADHD, Predominantly Hyperactive-Impulsive Type: if Criterion IB is met but Criterion IA is not met for the past six months. ADHD Classification Criteria Listed Criteria Needed for Different Subtypes Inattention Hyperactivity- Impulsivity Combined 18 6 6 Predominately Inattentive Predominately Hyperactive 9 6 0-5* 9 0-5* 6 *no more than 5 allowed ADHD Causes Primarily genetics (research still being done, but inherited factors have the most evidence) Prenatal maternal use of: Cigarettes Alcohol Other drugs NOT caused by the child s diet or environmental factors Environmental factors may intensify symptoms, but it does not cause the disorder 3
Treatment of ADHD Stimulant drugs such as methylphenidate (Ritalin) reduce disruptive behavior and improve concentration Improve compliance and decrease negative behaviors in many children Medications do not affect learning and academic performance Beneficial effects are not lasting following drug discontinuation Psychological therapy for ADHD involves Parent training Classroom management programs based on operant-conditioning techniques Aim to increase appropriate behaviors and decrease inappropriate behaviors Combined Bio-Psycho-Social Treatments Are highly recommended ADHD & ASD Both are considered to results in delays related to executive functioning They are not the same disorder! Autism is sometimes misdiagnosed as ADHD, especially for younger children This is primarily due to the behavior issues Once the other developmental delays, including communication, become more apparent the diagnosis is usually changed 4
ADHD & ASD Questions Dual diagnosis Medication Epilepsy Epilepsy Brain disorder where clusters of nerve cells, or neurons, in the brain sometimes signal abnormally NOT a mental illness or mental retardation More than 2 million people in US have had an unprovoked seizure Some can be controlled with medication In America, Epilepsy is as common as breast cancer, and is just as fatal 50,000 Americans die each year 5
Epilepsy Causes Multiple causes Brain chemistry Hereditary Other disorders Head injury Prenatal injuries Environmental causes Epilepsy Epilepsy and ASD Epilepsy occurs in 10 30% of individuals with autism It is unclear which ones occurs first Prevalence of epilepsy in children with autism is greater than chance Girls with autism have a higher incidence of epilepsy than boys May be correlated with lower cognitive skills in autistic girls Preliminary studies suggest that children with lower cognitive functioning and autism may be at a higher risk of epilepsy 6
Genetic Disorders Fragile X Tuberous Sclerosis Neurofibromatosis Rett Syndrome Angelman Syndrome Prader-Willi Syndrome Smith-Lemli-Opitz Syndrome Sotos Syndrome Williams Syndrome Genetic Disorders X chromosome related Father Ethnicity Fragile X 7
Fragile-X Syndrome Family of genetic conditions (caused by change in the gene called the FMR1 gene) Fragile X is the most common cause of inherited mental impairment 1 in 3,600 males and 1 in 4,000 to 6,000 females Impairments are more severe in males It is the most common known cause of autism IQ 30-55 in 80% Fragile-X Males Significant intellectual delay Range from learning disabilities to severe mental retardation and autism Variety of physical and behavioral characteristics Females 1/3 of the females have significant intellectual delay Others have moderate or mild learning delays Physical and behavioral characteristics are often expressed to a lesser degree Fragile-X Physical Features Distinctive facial features Males long faces and prominent ears Females prominent ears and jaw Connective tissue problems Enlarged testicles (males) Features usually appear after onset of puberty Appear to a lesser degree in females Not all features appear in each individual 8
Fragile X Syndrome 9
Fragile-X and ASD Fragile X syndrome can cause a child to have ASD Between 2% and 6% of all children diagnosed with autism, the cause is the Fragile X gene mutation Approximately 1/3 of all children diagnosed with Fragile X syndrome also have some degree of autism Fragile X syndrome is the most common known single cause of autism Tuberous Sclerosis Complex (TSC) Tuberous Sclerosis Complex (TSC) Tuberous sclerosis complex (TSC) is a genetic disorder that causes tumors to form in many different organs, primarily in the brain, eyes, heart, kidney, skin and lungs At least two children born each day will have TSC Nearly 1 million people worldwide Transmitted through genetic inheritance or as a spontaneous genetic mutation 1/3 of TSC cases are inherited 10
Tuberous Sclerosis Complex (TSC) The tumors are not cancerous, but they can still cause serious problems Most people with TSC have a normal life expectancy, but if left untreated the tumors can cause death Individuals with TSC can have cognitive skills ranging from gifted to profoundly mentally retarded About 60% of individuals with TSC have seizures 11
TSC and ASD ¼ and ½ of all children with TSC develop ASD The rate of TSC in children diagnosed with ASD is around 1% No known reason for the connection, but it is believed that abnormalities in brain development that occur in TSC sometimes interfere with the proper development of brains areas that are important for the development of social communication skills If TSC involve the region of the brain called the temporal lobes, there is an increased likelihood of ASD occurring The tumors alone are not generally enough though when they occur in conjunction with seizures there is a higher chance of ASD Neurofibromatosis 12
Neurofibromatosis (NF) Neurofibromatoses are genetic disorders of the nervous system that primarily affect the development and growth of neural (nerve) cell tissues Two types n NF1 1 out of every 4,000 births n NF2 1 out of every 50,000 births Cause tumors to grow on nerves and produce other abnormalities such as skin changes and bone deformities High heritability 30-50% of new cases are due to mutations in an individual s genes Neurofibromatosis Symptoms can be mile, but in some individuals there is damage to vital structures and can result in lifethreatening conditions Hearing loss is often the first sign in NF2 Signs in NF1 Café-au-lait spots of a certain number, size, and location The appearance of two or more neurofibromas (often resembling pea-sized bumps on the skin) Lisch nodules on the irises An optic glioma (tumor along the main nerve of the eye that is responsible for sight) Certain skeletal abnormalities (scoliosis) A family member with NF1freckling under the arms or in the groin Neurofibromatosis Possible complications: Seizures (up to 40% of children with NF1 have them) High blood pressure Scoliosis Speech impairment Optic nerve tumors (which can cause vision problems leading to blindness) Early or delayed onset of puberty Rarely, neurofibromas can become cancerous (3%-5% of cases) 13
NF and ASD The frequency of NF1 in individuals with autism varies from.2 to 14% (3 studies) This is greater than chance 14
Rett Syndrome Rett Syndrome Unique developmental disorder that is first recognized in infancy and seen almost always in girls, but can rarely be seen in boys In the past, has been misdiagnosed as autism, cerebral palsy, or non-specific developmental delay Occurs worldwide in 1 of every 10,000 to 23,000 female births Is a developmental disorder not a degenerative disorder Rett Syndrome Causes problems in brain function that are responsible for cognitive, sensory, emotional, motor and autonomic function This can include learning, speech, sensory sensations, mood, movement, breathing, cardiac function, and even chewing, swallowing and digestion Nearly all cases are caused by a mutation in the MECP2 gene Gene was discovered in 1999, prior to that Rett Syndrome was often misdiagnosed Life expectancy is typically no longer than 40 years of age 15
Rett Syndrome Diagnostic criteria: A period of apparently normal development before six 18 months of age A normal-sized head at birth followed by slowing of head growth between five months and four years Severe impairment in the use of language and loss of purposeful hand motion Repetitive hand movements that include one or more of the following: hand washing, hand wringing, or hand clapping Shaking of the chest or torso, particularly when the child is agitated or upset In children able to walk, an unsteady, stiff-legged, widebased gait 16
Rett Syndrome and ASD Children with Rett Syndrome exhibit symptoms similar to those diagnosed with classic autism Toe walking Lack of eye contact Weakened muscle tone Difficulty interacting with others Not the same disorder Children with Rett Syndrome exhibit unique hand movements n Fidget, wring, clasp, squeeze or tap hands n Often suffer from apraxia Angelman Syndrome Angelman s Syndrome (AS) Angelman Syndrome is a neurogenetic disorder first described by English Physician Harry Angelman in 1965 Today, the Angelman Syndrome Foundation is aware of approximately 1,000 cases in the United States, but thousands more are believed to exist throughout the world, as yet undiagnosed 17
AS Causes AS is most often caused by a deletion on the maternal 15 th chromosome Can also be caused by dual imprinting, when two copies of the same chromosome are copied to the same strand of DNA Angelman Syndrome is a deletion of DNA from the 15th chromosome. This deletion occurs on the maternal (mothers) side of the DNA helix, though is 99% of the time no indication of anything wrong with the mother's DNA. AS AS is characterized by: Severe intellectual disability Speech impediment Sleep disturbance Unstable jerky gait Seizures Usually a happy demeanour AS Breakdown of Characteristics Always seen (100%) Severed intellectual disability Profound speech impairment Ataxia of gait Behavioral uniqueness n Happy demeanor n Easily excitable n Hand flapping movements n Short attention span and hyperactivity 18
AS Breakdown of Characteristics Usually seen (more than 80%) Small head size Seizures (abnormal EEG) AS Breakdown of Characteristics Sometimes seen (20% - 80%) Flat occiput (flattened back of head) Protruding tongue Tongue thrusting Suck/swallowing disorders Feeding problems during infancy Wide mouth, widely spaced teeth Frequent drooling Excessive chewing/mouthing behaviors Scoliosis (curvature of the spine) Strabismus (crossed eye) Hypo pigmented skin, light hair and eye color (compared to family), a feature in deletion cases Wide based gait (feet far apart with flat, out turned feet) Tendency to hold arms up and flexed while walking Increased sensitivity to heat Sleep disturbance Attraction to/fascination with water 19
AS and ASD There is no known genetic cause for ASD, but there has been interest in chromosome 15 (impaired chromosome in AS) Share some behavioral characteristics There are some children with AS that present with the behavioral characteristics associated with autism Of those children that present with both syndromes, those with lower cognitive functioning manifest more severe behaviors Prader-Willi Syndrome 20
Prader-Willi Syndrome (PWS) A disorder of chromosome 15 Prevalence: 1:12,000-15,000 (both sexes, all races) Major characteristics: hypotonia, hypogonadism, hyperphagia, cognitive impairment, difficult behaviors Major medical concern: morbid obesity PWS Characteristics Appetite disorder Obsession with food Disordered appetite/satiety function Weight management Low muscle mass Behavior issues Difficulties with transitions and changes Obsessive-compulsive symptoms Delays in motor and speech development Cognition IQs range from 50 to 105 with an average of 70 Those with cognitive skills in the normal range typically have learning disabilities PWS Other Common Concerns Strabismus Esotropia is common; requires early intervention, possibly surgery Scoliosis Can occur unusually early; may be difficult to detect without X- ray; curve may progress with GH treatment. Osteoporosis Can occur much earlier than usual and may cause fractures; ensure adequate calcium, vitamin D, and weight-bearing exercise; bone density test recommended Diabetes mellitus, type II Secondary to obesity; responds well to weight loss; screen obese patients regularly Other obesity-related problems Hypoventilation, hypertension, right-sided heart failure, stasis ulcers, cellulitis, and skin problems in fat folds 21
PWS Other Common Concerns Sleep disturbance Hypoventilation and desaturation during sleep are common, as is daytime sleepiness; sleep apnea may develop with or without obesity; sleep studies may be needed Nighttime enuresis Common at all ages; desmopressin acetate should be used in lower than normal doses Skin picking A common, sometimes severe habit; usually in response to an existing lesion or itch on face, arms, legs, or rectum. Best managed by ignoring behavior, treating and bandaging sores, and providing substitute activities for the hands. Dental problems May include soft tooth enamel, thick sticky saliva, poor oral hygiene, teeth grinding, and infrequently rumination. Special toothbrushes can improve hygiene. 22
PWS and ASD Several behavioral features of Prader-Willi syndrome including language, motor and developmental delays, overlap with features of autism Smith-Lemli-Opitz Syndrome 23
Smith-Lemli-Opitz Syndrome (SLOS) Genetic disorder that affects the development of children both before and after birth The syndrome was first described in 1964 in three boys with poor growth, developmental delays, and a common pattern of congenital malformations including cleft palate, genital malformations, and polydactyly (extra fingers and toes) SLOS Children with SLO/RSH Syndrome are unable to make cholesterol, an essential nutrient that is not provided by the mother to the baby before birth Children with SLO/RSH Syndrome continue to have trouble with development and general health after birth SLOS Common Problems Microcephaly (small head) Extra fingers or toes Apparently low-set ears Small, upturned nose Webbing between 2nd and 3rd toes (syndactly) Abnormal palmar creases (usually single) Cleft palate Hypospadias (genital malformation in boys) Cataracts Undescended testicles Blepharoptosis (drooping eyelids) Heart defects Micrognathia (small chin) Pyloric stenosis Short thumbs Hirschsprung disease (absent nerves in colon) Feeding problems can result in failure to thrive 24
SLOS Causes SLOS is caused by mutations in the DHCR7 gene on chromosome 11 (11q12-q13) Inherited as an autosomal recessive Mendelian disorder SLO/RSH Syndrome is one of the most common autosomal recessive disorders 1 in 20,000 births 25
SLOS and ASD Autism has been documented in a number of individuals with SLOS A recent study of 26 individuals with SLOS found that 17 of them (53%) met criteria for autism Sotos Syndrome Sotos Syndrome Sotos syndrome is a genetic condition causing physical overgrowth during the first years of life Children with Sotos syndrome are often taller, heavier, and have larger heads than their peers Rapid physical development is often accompanied by delayed motor, cognitive and social development Muscle tone is low, and speech is markedly impaired 26
Sotos Syndrome Breakdown of Characteristics Features seen in most children (80%-100%) Macrocrania (large skull) without megalencephaly (large brain) Dolichocephaly (high, narrow skull) Characteristic structural changes in the brain on MRI (extra fluid, midline changes) Prominent forehead, "receding hairline Apparent hypertelorism (eyes look wide-spaced despite normal measurement) Rosy coloring over the cheeks and nose High arched palate (roof of mouth is narrow and arched upward Increased birth length and weight Excessive growth in childhood Disproportionately large hands and feet Low muscle tone Developmental delay Expressive language delay Sotos Syndrome Breakdown of Characteristics Features seen in the majority (60% -80%) Advanced bone age (above 97th percentile Premature tooth eruption, soft enamel Poor fine motor control Down-slanting palpebral fissues or "antimongoloid slant" (eye openings are lower in outer corners than by nose) Prominent, pointed chin I.Q. in the normal range (>70 I.Q.) Learning disabilities Frequent upper respiratory infections Behavioral disturbance (anxiety, depression, phobias, sleep disturbance, tantrums, irritability, stereotypies, inappropriate speech, withdrawal, hyperactivity) Sotos Syndrome Breakdown of Characteristics Features seen in the minority (under 50%) Hyperbilirubinemia (newborn jaundice) Persistent feeding difficulties and/or reflux Dislocated hips or club feet Nystagmus, strabismus (eye movement or focusing problems) Autonomic dysfunction (flushing excessive sweating, poor temperature control) Seizures Constipation, megacolon Scoliosis (curvature of the spine) Heart defects 27
Sotos Syndrome Breakdown of Characteristics Occasional or possibly associated features Abnormal EEG Glucose intolerance (pre-diabetes) Thyroid disorders Hemihypertrophy (uneven limb length or body mass) Neoplasms (tumors and cancers) Sotos Syndrome Causes Scientists linked Sotos syndrome to mutations in a gene called NSD1 (Nuclear SET domain 1) This gene on the long arm of chromosome 5 was missing or altered 28
Sotos Syndrome and ASD Sotos syndrome is an overgrowth syndrome and should be considered in individuals with autism and macrocephaly Williams Syndrome Williams Syndrome (WS) Williams syndrome is a genetic condition that is present at birth and can affect anyone Microdeletion on chromosome 7 affecting one of the alleles of the elastin gene WS affects 1 in 10,000 people worldwide Estimated 20,000 to 30,000 people in the United States It is characterized by medical problems, including cardiovascular disease, developmental delays, and learning disabilities They also can have striking verbal abilities, highly social personalities and an affinity for music 29
Common Features of WS Characteristic facial appearance Small upturned nose Long upper lip length Wide mouth Full lips Small chin Puffiness around the eyes Heart and blood vessel problems Can be life-threatening Hypercalcemia (elevated blood calcium levels) Common Features of WS Low birth-weight / slow weight gain Feeding problems Irritability (colic during infancy) Dental abnormalities Kidney abnormalities Hernias Hyperacusis (sensitive hearing) Musculoskeletal problems Overly friendly Developmental delay, learning disabilities, & attention deficit disorder 30
WS and ASD Many people with Williams Syndrome exhibit some autistic-like behaviors: Developmental and language delays Problems in gross motor skills Hypersensitivity to sounds Being picky eaters Perseverating 31