what about health 1: genetics - oregon health & … about health 1: genetics. these...

The title of this presentation is What About Health. I’m Dr. Robert Nickel. In this presentation I will discuss a number of health and mental health issues related to children with ASD.

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What About Health 1: Genetics

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My objectives in this presentation are to discuss…… (as per slide)

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As a reminder, this talk addresses the Oregon Commission on ASD or OCASDrecommended competency on knowledge re medical and mental health conditions. Knowledge should include potential….. (as the slide)

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And this is another reminder. DSM 5 requires diagnosticians to list specifiers to a diagnosis of ASD which include association with any known medical or genetic condition (for example, Fragile X syndrome) or environmental factor (for example, fetal alcohol exposure), and any neurodevelopmental, mental, or behavioral disorder. With DSM 5 we now can list ADHD or anxiety disorder as co-occurring conditions.

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The prevalence of ASD is relatively high and has increased over the last few decades, The current number of 1:68 is based on the Centers for Disease Control’s Autism and Developmental Disabilities Monitoring Network or ADDM. There is a very high concordance rate for ASD in identical twins and high recurrence rate in siblings. Both of which support a strong genetic basis for ASD. In addition, there is an increase in a number of learning and mental health conditions in other family members.

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A critical question is what causes autism. A number of theories about environmental causes have been discredited including vaccinations. We can currently identify a “medical” cause in up to 15-20% of children. These include a number of different genetic mechanisms such as single gene disorders, small duplications or deletions of DNA and chromosomal disorders such as Down syndrome. In individuals with 15q11-13 dupl, >40% have an ASD but in individuals with ASD only 1-3% have the 15qdupl.In individuals with 16p11 del, a high % have an ASD, but in individuals with ASD only 1% have 16p11 del.50% of individuals with Smith Lemli Opitz syndrome have an ASD, but <1% of individuals with ASD have SLO.ASD is also associated with non-genetic mechanisms such as perinatal infection with cytomegalovirus or CMV and several risk and protective factors although these do not establish causation.

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Tuberous Sclerosis is an autosomal dominant disorder causes by one of 2 genes, TSC 1 and TSC 2. This slide list a number of the features associated with TS and the picture demonstrates a typical hypopigmented spot. Initial suspicion of TS requires a careful skin exam including use of the Wood’s lamp.

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Dysmorphology refers to the science of identifying minor variation in physical development. Remember, beauty is in ….. (rest as per slide)

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This slide presents one minor anomaly or dysmorphic feature, widely spaced eyes or hypertelorism….. (rest as per slide)

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The clinician should be aware of certain definitions and issues related to identification of patterns of development that may assist with syndrome identification. Major ….. (rest as per slide)

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This slide demonstrates a major anomaly, syn (joined together) poly (extra) dactyly(fingers and toes)

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Bilateral single transverse palmar creases are present in up to 3 % of individuals in the population, however, bilateral single transverse creases can also be one finding in children with Down syndrome

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Infants with Down syndrome are often easily identified by their pattern of minor anomalies. Children with Down syndrome or Trisomy 21 often have bilateral epicanthal folds, up-turned palpebral fissures, short nose and small ears. These children may also have small hands, short 5th finger and single palmar creases.

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Another genetic disorder that is commonly associated with ASD id Fragile X syndrome. Fragile X is present in 1/2000 males in the population, however, in 1-3% of individuals with ASD. And up to 25% of males withFragile X meet criteria for ASD.The characteristic physical features are macrocephaly, long face, prominent jaw and macro-orchidism. These features are not present in early childhood. The IQ is variable with as many as 25% with IQs above 70. Behaviroal features include shyness, avoidance of eye contact, cluttered and perseverative speech.Female carriers of Fragile X may have significant developmental problems due to the random inactivation of the X chromosome.

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This slide reviews the findings in another genetic syndrome associated with ASD, PTEN. PTEn is a tumor suppressor gene. It is associated with macrocephaly, head sizes 3 or more standard deviations above the mean. One study has reported overgrowth of white matter connections as well as spots where white matter development is clearly abnormal….. (rest as per slide)…. They may have breast cancer, thyroid problems, skin problems

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Rett syndrome is caused by mutations in the MECP2 and less frequently Xq28 genes. Nearly all individuals with Rett syndrome are females…… (rest as per slide)

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One way to categorize children with ASD is whether they have complex autism (apparent syndrome) or simple autism (no apparent syndrome). This slide reviews the features of children with complex autism. They are more likely to be dysmorphic or microcephalic or have structural brain anomalies. Unlike simple autism where there is a marked male predominance, with complex autism there is nearly a 1:1 male to female ratio. In addition, children with complex autism have a gradual onset to symptoms and not a late regression. They are more likely to have an associated intellectual disability. As many as 30% of children with complex autism will have a specific etiologic diagnosis but few children with simple autism will have an identified medical or genetic cause.

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When should you suspect a genetic disorder? This slide lists a number of findings that should strongly suggest the presence of a potential genetic disorder (rest as per slide)

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This slide lists findings that should strongly suggest the presence of a metabolic disorder as a cause for the child’s developmental problems. The typical autistic regression occurs between 18-24 months and involoves loss of language skills (several words used consistently for 1 month or more) and change in behavior (limited eye contact, hyperactivity, irritability) with little/no change in neuro-motor abilities.If the child is a girl with seizures think Rett syndromePhysical features include organomegaly, enlarged liver and/or spleen

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These are the recommendations for medical/laboratory evaluation of childrenwithASD from the American College of Medical Genetics and GenomicsRefer all multiplex (more than one child with an ASD) families to medical geneticist for evaluation.See handout on dysmorphic features, surface evaluation for minor anomaliesCMA 10-15%, Frag X 1-5%, MECP2 4% of girls, PTEN 5% >2.5 SD, other 10%Studies have reported increased rate of iron deficiency. Other studies have linked iron deficiency with sleep problems including restless legs or periodic leg movements and fragmented sleep. One study has reported improved sleep latency and total sleep time with iron supplementation.

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These recommendations are adapted from the American College of Medical Genetics and Genomics which also have been adopted by , the American Academy of Pediatrics and the Autism Treatment Network

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This slide presents a book metaphor for genetic testing…… (as per bullets on slide). Current practice is to obtain CGH microarray on all children with undiagnosed ASD. Whole genome analysis is primarily of research interest at present.

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what about health 1: genetics - oregon health & … about health 1: genetics. these...

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