 Welcome to our next to last webinar, Genomics and Autism Spectrum Disorder. We have three presenters who worked on this paper for the Journal of Nursing Scholarship, the first being Nora Johnson from Marquette University in Milwaukee, Wisconsin. She's assistant professor there. And she also earned her master's in PhD in nursing, having earned a bachelor's degree from the University of Toronto. In addition to her research on families of children with autism spectrum disorder, she consults in the Education Department at Children's Hospital at Wisconsin and works as a pediatric nurse practitioner at the Marquette Neighborhood Health Center. The second presenter today will be Dr. Ellen Giorelli from Drexel University of Philadelphia, Pennsylvania. She is a program director post-baccalaureate certificate in nursing care of ASD at Drexel University. And she has co-chaired an NHGRI-funded R21, Examining Uncertainty and Genome-Wide Testing of Patients with ASD. She's recently authored a chapter in the genetics and genomics and nursing book by Kenner and Lewis on genetics of ASD, and she is a past president of ISOL. She also has been a PI of Pennsylvania Autism and DD Surveillance Program at UPenn, 2006 through 2010. Our third co-author, Dr. Catherine Rice, is an epidemiologist and developmental psychologist with a developmental disabilities branch at the National Center on Birth Defects and developmental disabilities at the Centers for Disease Control and Prevention. She will be available for questions following the webinar. She received her undergraduate degree in psychology from Emory University and her doctorate in developmental psychology from Boston College. She has worked with people with autism spectrum disorder through teaching, diagnostic assessment program, planning, consultation, training, and research for about 20 years. So we have a wealth of expertise on this presentation today, and we look forward to hearing more. Nora? Hi everyone. Thanks for joining us. The purpose of this webinar is to understand the current state of the evidence regarding translation of genetics and genomics into the nursing care of children with ASD. ASD is a collective term for pervasive neurodevelopmental conditions characterized by atypical development in socialization, communication, and behavior. The term autism was first introduced as a developmental disability or pervasive developmental disorder in 1980 in the DSM-3. PDD, not otherwise specified, was added in 1987, and Asperger's disorder was added as a type of PDD in the 1994 edition of the DSM. So with the redefining and recognition of ASD, there have been an increase in the number of people identified with ASD from the 1940s until the 1980s. Autism primarily referred to more severely affected individuals with autistic disorder, and it was thought to be rare affecting approximately one in every 2,000 children. Now several studies using the ICD-10 and DSM-4 criteria have identified autism and the wider spectrum with surprising consistency at 6 to 7 of 1,000 children. With the best estimate now being greater than 1%, and as high as 2.6% in some areas of Europe and Asia, four to five boys are affected for every girl. Today there is an increasing appreciation of the causal heterogeneity in the expression of ASDs along numerous phenotypic dimensions. The core domains associated with the ADD, ASDs, the social communication, restricted repetitive behaviors are distributed in a more continuous way in the population. For example, characteristics of autism such as attention to detail are adaptive with mild phenotypic expression, but are problematic when severely expressed or in interaction with other environmental factors. It's widely accepted that the ASDs are highly heritable. Rosenberg and colleagues reported identical twins shared 60 to 90% of autistic traits compared to fraternal twins who only shared 0 to 10%. Sibling reoccurrence is estimated to be as high as 19%, and in addition, concurrence of ASD and single gene disorders has been observed, adding to the evidence that genetic factors play a role in ASD. To date, no single risk factor explains the prevalence change over time. Environmental factors play a part in determining whether ASD will develop in a particular individual. Studies have implicated exposure to high levels of environmental pollutants such as pesticides. Two studies looked at complications during pregnancy. One found a positive relationship between viral infections and an increased incidence of ASD, and one found a relationship between maternal stress and an increased incidence of ASD. Likewise, artificial insemination and ovulation-inducing drugs were significantly associated with having a child with ASD and mothers older than 35 years old in one study. So an exciting new area of research relates to environmental epigenetics, the study of factors that control gene expression by chemicals that surround the gene's DNA and affect genetic activity. Shula and others found that histone methylation is different in persons with ASD compared to controls on genes regulating neuronal connectivity, social behaviors, and cognition. Another study is exploring if epigenetic changes from methylation related to environmental exposure during pregnancy might increase the risk of ASD. Now I'll turn it over to Ellen. A few slides back, Dr. Johnson talked about heritability and the higher incidence among twins. These early studies and replication studies warranted a close server, careful analysis of the genetics of ASD. And as with other diseases, the study of genetics holds props to the discovery of definitive case causes, which can hopefully lead to definitive treatments and hopefully cures. But parents in collisions may ask, why is it so difficult to find genetic answer when we know so much about the human genome and genetics analysis in general? Well, genetics alone is a very complicated study and if you have epigenetics and environmental factors, this makes finding a definitive answer much more elusive. But some facts that complicate the discovery are listed on the slide in front of you. For example, individuals are 99 and more percent identical genetically. People are highly heterogeneous and ASD is a highly heterogeneous disorder. Until very recently, we had limited ability to search through the human genome to find differences between people and among people. Often ASD is not due to single gene defects and there is not often a one-to-one relationship between a genetic risk and the outcome. And research in the genetics of ASD is interested in this 1% difference that is so difficult to pin down. Next slide. It's also very little is known about the diversity in systems-level brain architecture. And the new initiative that was announced very recently this past spring by Dr. Collins out of NIH to map the human brain in an analogous fashion to the mapping of the human genome has been very encouraging to neurobiologists who wish to study the neurobiology of a multispective disorder. We are not sure though what is normal and what is atypical in every aspect of human brain structure and function. Genetic influences emerge from rare variants that may have very small but cumulative effects with ASD. And research in ASD genetics is in its infancy. We need ways to connect genetic variation to specific behaviors. And then we have to understand how to apply this information to ASD and the subgroups of ASD. But researchers are following very significant leads that come out of the literature. And recently you may have seen some. One in 2012 stated that father's age was linked to the risk for autism and schizophrenia. And another grandfather's age is linked to the risk of autism. It was 2013. And very recently, in fact two days ago in the New York Times it was reported on how autism is tied to creases in the placenta and this is linked with disfounded families at high genetic risk for having an autistic child. So there's lots more to be studied. Next slide. So there are two general approaches to research in genetics of ASD. They are to examine single gene mutations and to look at variations in genetic sequences. Single gene mutations might be those very rare mutations that are known to cause syndromes with autistic symptomatology. Rare syndromes sometimes can be identified as caused by a specific genetic mutation and therefore looking at these single gene mutations we can understand the genetics of some cases of ASD. But it's unlikely that there is only one path in these genomic syndromic disorders. These syndromes have characteristics of their own and in addition they have other characteristics that are not associated with ASD. So quite complicated. The other approach to research is looking at variations. We examine the differences in genetic sequences by comparing them to some reference sequence that's considered to be from a normal or from a person that does not have ASD. We look for single nucleotide polymorphisms, very specific and small differences in structure. Structural gains and losses of genetic material called copy number variance. And some of these variations may be common and others may be quite rare. But most important is that the nature of some of these variations eludes us. We just don't really understand right now what these variations mean with respect to the risk for an individual developing or explaining the case of ASD. This needs to be confirmed. Next slide. Among the medical conditions and syndromes that are caused by single gene mutations, we know some specifically. Individuals with the following conditions account for only 5 to 10% of the cases. X chromosome trisomies, including client fetal syndrome. Fragile X at RET syndrome. Tuberous sclerosis. Smith vaginas. Anglement and prodder willy and velocardiofacial conditions are those single gene disorders that are also associated with ASD. Next slide. In the case of variations, geneticists look at structural gains and losses in genetic materials which are called copy number variance. There is evidence that large de novo copy number variance. And by de novo, I mean those that are not known to be inherited from a parent. Account for about 6 to 10% of cases of ASD. And these large variants are from about 500 kilobase pairs in length. These variants carried large but clearly identifiable risks for developing or having ASD. And inheritance assessments suggest that about a third of these variants are in fact new and not inherited. And there are very new hotspots that are emerging in the scientific literature. And in particular, researchers are looking at chromosome 15, the long arm of chromosome 15. It's three specific genes that are implicated in about 1 to 2% of patients who are diagnosed with ASD. And these are all found on chromosome 15. So this is a very cute interest among geneticists and genomic investigators. And the illustration of the lower right side just shows you how one would examine differences at that minute molecular level between normal reference DNA and the test DNA, which would be that sample from a person who is affected with autism. And you'll see the graph on the lower right, very lower right, shows where a deletion of some material is indicated by a rise. And in the normal reference, it's missing in the test case. And in the second bullet, you'll see a similar reaction. Next slide. Other copy number variants are of intense interest to investigators. On the short arm of chromosome 16, researchers are looking at deletions and duplications that have been linked with 1% of cases of idiopathic or unknown cause of ASD. Duplications on the long arm of chromosome 7 have strongly been associated with autism. And this is a region that is implicated in bullying syndrome. And also, on chromosome 7, we know that speech and language disorders have been linked. And we know that in autism spectrum disorder that there are often significant deficits in speech and their language complications. And there are four regions on several chromosomes that have been identified as denovo and are associated with cases of ASD. And this is on chromosome 1, 15 and 16. And you'll note that I added an asterisk here next to chromosome 15 because we also know that disorders of anxiety and epilepsy have been linked to this particular region of chromosome 15. And anxiety and epilepsy are comorbid disorders that are associated with the diagnosis of autism. Next slide. We can also look at specific brain functions to understand the genetics of autism rather than looking specifically for autism causes. We look at other things that are causing characteristics that are typical for patients with ASD. Chromosome 7 is being studied to look at cerebellum function and development. Chromosome 4, 5 and 15 are being examined for brain cell migration, differentiation and synapse formation. We're looking at chromosome 3 to understand stress response and the development of social skills. Chromosome 7 is being examined for neuronal migration in the developing brain. And chromosome 17 is studied for its role in serotonin transport, which has been implicated in cases of ASD. So there are several ways that we can approach the genetics of understanding this condition. Next slide. Fully understand the genetics of ASD. We're going to have to also examine the genetics of other features that co-occur with autism spectrum disorder. The statistics on the left side of the screen represent some of the numbers that we reported from the Statistic Disease Control Surveillance Program in 2012 that list the prevalence of associated disorders with our cases of ASD. Notice that abnormalities in mood and effect occur in 68% of our cases of ASD have been linked to disorders on chromosome 17. And you'll see on the right side of the screen obsessions, compulsions, depression. Depression would be considered abnormality of mood and effect. So one way that we can understand the genetics of ASD is to look at some of those comorbid characteristics of the disorder and investigate what genetic factors that contribute to the development of comorbid features. Next slide. An analytic test called chromosomal microarray analysis is currently available to aid in the diagnosis of ASD. It's also called comparative genomic hybridization. This is a method for the analysis of copy number variants, these gains and losses in the entire genome of a person who's affected. It is now considered a medically necessary test when a child presents with the possibility of any one of those major syndromic disorders in clinical practice. In 2002, Manning and Huggins reported a consensus statement that said that chromosomal microarray analysis is now considered a first tier clinical diagnostic test for individuals with developmental disabilities or congenital abnormalities. And this was reported in the American Journal of Human Genetics. This test is now being offered to patients, to parents to take for their children, who present for definitive diagnosis of ASD or other syndromic disorders. It is considered medically necessary for diagnosing a genetic abnormality in children with a parent non-syndromic ASD when the biological test for the metabolic disease is non-diagnosis, and if the genetic analysis for Fragile X syndrome, for example, is negative. Then also it's recommended to be taken if the child has one or more of the following conditions, a major malformation, a single major malformation, or multiple minor dysmorphologies, a single major malformation, and multiple minor malformations. If the result of a genetic test has the potential to impact clinical management of the patient, and if the test is requested by the parents. Next slide. So I added this slide to wrap up the last description of chromosomal microarray analysis to give you some insight into what parents think about the causes of ASD. In a Selkirk study in 2009 reported the following statistics. Parents perceived that the causes of ASD were in 73% of the cases caused by some genetic factors. Only 10% of those parents had actually seen a genetic professional related to their child's ASD. So 70% of these parents who were surveyed believe that genetics is at play with their child's disorder. Pregnancy and delivery problems only 23%. Childhood illnesses 20%. Vaccines 20%, 27% still relatively high. Diet, environmental factors all kind of low. And the age at birth of the mother and father unusually low given that what we know about the age of fathers and its implication in risk for ASD. But I pointed that first statistic to suggest that parents might be coming into clinical practices now and asking you for access to the chromosomal microarray analysis test, given that it is being recommended in clinical guidelines. And with that I will turn the presentation back over to Dr. Johnson to continue to discuss this particular issue. So nurses need to know the genetic and genomic research methodologies as nurses inform and counsel patients for participation in clinical trials. And nurses caring for families of persons with ASD need to understand the implications of participation in different areas of research, behavioral, biological. The International Society for Autism Research fosters necessary interdisciplinary collaboration. And there is collaborative consortiums listed here that increase the power of the genetic studies. The Simon Simplex Community research focuses on families with only one child with ASD. Their research helps identify if genetic changes are inherited from the parent or the result of de novo mutation. And the research offers the potential to connect environmental and genetic links to ASD. So there's many research methodologies and implications for participation. For example, in some the intent of the research may only be to aggregate the findings of potential genetic associations across patients for reports for scientific literature. And these aggregate findings may offer no clinically useful information for symptoms or prognosis or therapeutic interventions in the short term for the families. And to date the reason for this lack of clarity for prognosis is for the child's ASD relates to the complex nature of aligning genes with the behavioral symptoms. The phenotype, which also limits the development of the clinically valid genetic test. Education on ASD and genetic literacy are needed for nurses to have adequate knowledge and skills to assess genetic risk for ASD and to advocate for at-risk families. One educational resource to help meet this goal is the National Genetics Education and Development Center. A case-based story on their website describes ASD as a condition with multi-factorial etiology and a link to a nursing competency in genetics. The real-life example helps nurses conceptualize how to apply the complicated science of genetic risk to a real case. And in order for services to be directed to those in need, nurses and other healthcare providers need the knowledge of both the genetic risk factors as well as the signs and symptoms of ASD. Nurses can also collect a family history across generations assessing for the broader autism phenotype in apparently unaffected family members across generations. So implications for practice, nurses can assess for possible ASD in all childhood encounters by determining how the child communicates, interacts, behaves, learns, and plays. Recent efforts have focused on improving the early recognition of autism and for screening all children with algorithms in the U.S. and in the United Kingdom. But without a definitive cause for ASD, as Dr. Gialli mentioned, parents are left to come to their own interpretations for the cause, and their beliefs may affect future decisions they make about healthcare. We do know that parents do experience stress during the diagnosis, and they really do require a plan for lifelong behavioral interventions for their child with ASD. So children with evidence of ASD should be referred for comprehensive diagnostic evaluation with behavioral observation assessment tools. As there is no definitive diagnostic test, obtaining a timely diagnosis is important so that children can begin receiving evidence-based therapies as soon as possible. Early evidence-based therapies improve the chance of optimal functioning and health. The Centers for Disease Control has information for new parents, healthcare professionals, and early childhood education providers on early developmental milestones, concerns needing follow-up, early developmental screening, and starting developmental therapies as soon as possible. In America, one source for obtaining therapies early is the public education system. So in summary, ASD researchers continue to identify genes involved in ASD, with the current evidence suggesting that there's many genes on different chromosomes that may be involved, and that chromosomal disorders and syndromes are risk factors for ASD. Nurses will continue to play an important role in research, education, and practice for families of children with ASDs. There's several clinical resources listed here, and that ends the presentation. I'll hand it back over, I think, to the Question Center and our next presenters. Thank you. Thank you, Nora and Ellen. I appreciate it. I'm going to open up the microphone for Dr. Rice as well, and Ellen and Nora. I have not received any questions that have been typed in yet, so if you want to make any additional comments in the two minutes you have left, please feel free to do so. Hi, everybody. This is Dr. Kathy Rice. Thank you, Dr. Johnson and Jarelli, for your wonderful presentation. I just wanted to reiterate that there is a lot of information about early developmental monitoring and signs for concern about autism and other developmental disabilities on the Centers for Disease Control website. In addition, we do have a CE credit program that is available for professionals about early identification of autism. It's called the ACT Curriculum, the Autism Case Training. So if you are in need of CE credits, as well as some good information, I definitely would encourage you to look at the CDC.gov-slash-act-early website for the ACT Curriculum. Thank you. I've received one question that we'll be able to deal with before moving on to our next presenter. I'll jump in in terms of a little bit about racial and ethnic differences in autism. At this point, we really don't have any solid evidence that there are differences by race and ethnicity. We do see differences in prevalence of children identified across race and ethnicity, but over time we have seen some of the greatest increases in identified autism among children who have been under-identified in the past, African-American children, Hispanic children. And so we're seeing the gap between different race and ethnicities close a little bit over time. And so in the basic, is there even any phenotypic variation across the conditions? That is really not clear, but there's not much evidence, with the exception of intellectual disability identified more often among African-American children with autism, which also mirrors the intellectual disability population. But in terms of genetics, I don't know of any association. I will not be able to answer the remaining questions, but we'll turn those over to our presenters today, and thank you very much for a wonderful presentation. Next on our docket is to have Cindy Prouse talk about an update of childhood genetic disorders. And Cindy, I will turn it over to you to begin your presentation. I do want to tell you a little bit about Cindy in that she is a genetics clinical nurse specialist at Children's Hospital in Cincinnati, and her career focus has been on translation of genetic, genomic information and technology into clinical practice. With both NIH and HRSA funding, she has created, developed and sustained the genetics education program for nurses for over 10 years, and this program has provided genetics education primarily web-based to over 3,000 nurses both nationally and internationally. She is co-PI or co-investigator on several pharmacogenomic and clinical genomic studies, and we appreciate your presentation today on an update of childhood genetic disorders. Okay, thank you. I'd like to start off by acknowledging and thanking my co-authors, Dr. Rob Hopkins and Sylvia Barnoy and Dr. Marsha Van Riper for the article. The webinar, however, is going to try and incorporate key points from the article but not repeat much of the content. I'm going to use a case example to illustrate ways nurses can incorporate genetics and genomics information into practice and briefly discuss the impact of new technology and national recommendations on our definition of childhood genetic disorders. Childhood genetic disorders are diseases or syndromes caused by variants affecting nuclear or mitochondrial genes or combinations of variant genes and environmental factors or changes in the number or structure of one or more chromosome or chromosomal regions, and these disorders manifest prenatally or before 18 years of age. So disorders is more of an umbrella term. If you go to the online Mendelian inheritance in man and simply type in children to try and identify those conditions in which that might manifest in childhood, you can see there's almost 2,500 in the database. A couple of those conditions just even on the first page is a screenshot are clear Mendelian inheritance disorders that oftentimes are conditions that are discussed in nursing curricula like neurofibromatosis, which is autosomal dominant, used to be called Elfman's disease, but we know that's not the case, and PKU, which literally has been a nursing curricula for a very long time. And then there are other conditions like autism, which we just heard about, that is just now finding its way into OMIM relatively recent in comparison to how long I've been in genetics. So as they start to understand some of the genetic susceptibilities. And one of the problems with but exciting aspects of genetics and genomics is the rapid pace at which knowledge about these conditions change. And so if it has been a while since you've received instruction about genetics or genomics or it's been a while since you cared for a child with a particular genetic disorder, I encourage you to use the available resources to update your knowledge. I can't even begin to memorize all the genetic disorders and all the genes that are associated with these disorders. So my talk highlights some of my favorite resources that I hope you'll be able to use in your practice or research or educational settings. This is a screenshot of content about PKU in the online Mendelian Inheritance in Man. And when I started my role as a genetics clinic specialist back in 1990, this was the only real resource I had, and I found it essential but also overwhelming. Because as you can see, there are, it is a summary of key cases and studies, and it can be somewhat, it's written at a high level. And when you're just starting off in genetics, it can be a little bit overwhelming, but it's a wonderful resource and obviously you have all the references there that you could possibly want. On the other end of the spectrum, I'm not sure when it first became available, but several years after I had been in genetics, the Genetics Home Reference was developed by the National Library of Medicine. And this is a wonderful resource, it's consumer friendly information about the effects of genetic variations on human health. And if you're new to genetics, it's been a while since you've learned about autosomal recessive inheritance, autosomal dominant, chromosomes, genes, mutations, polymorphism, all that. This handbook provides a lot of good introductory information about that. They'll help you when you go to read the literature. Also, this website contains a list of 800 health conditions, diseases and syndromes, and these are nice reviews that are easy to understand and very clinically relevant. And this is a screenshot from Genetics Home Reference about PKU. And every condition has this question and answer format. So what is PKU or what is whatever condition that's being highlighted in the resource? How common is it? What genes are related to PKU? How do people inherit it? Where can I find information about diagnosis or management? Where can I find additional information about PKU? What other names do people use for PKU? And what if I still have specific questions? So there's a lot more resources. So the public will use this resource, but also I think it's a very valuable resource for nurses, because it's a quick place to go to get an overview of what's current. And then probably one of my favorite resources that started to become available during my career in genetics is gene reviews. And it provides a very comprehensive review of a particular condition that's written by experts. It's peer reviewed, it's regularly updated, and it's really the most comprehensive and clinically useful resource for my purposes. And this one, again, this is about PKU, but it shows different types of information. And I've been, like I said, in genetics for over 20 years, and during this time I've seen many instances of what's displayed on this screen. And that is once the gene has been identified for a particular disorder, and patients with milder characteristics of the disorder are found to also have variance in the gene of interest, the name of the disorder becomes broader to cover the spectrum of presentation. And so as you can see here that this phenylalanine hydroxylase deficiency is now the name given for this umbrella or group of disorders caused by changes in the phenylalanine hydroxylase gene. And classical PKU is just one of those disorders within that spectrum. So now I'll talk about a case to try and show what a relatively common childhood genetic disorder in my world, one in 4,000, is common for genetic disorders. And compared to some that are one in 100,000 or just a handful known internationally. So this is a fictitious case example, but it is based on my years in various multidisciplinary clinics. And so I'm talking about a five-year-old female who has come in for evaluation of hypernasal speech in the multidisciplinary velofarangial insufficiency clinic. And children that come into this clinic have a very specific speech disorder where a lot of air comes out of their nose when they're trying to produce consonants. And if you've ever heard a child with cleft palate, you'll know what hypernasal speech sounds like. And we always have a clinic nurse in this clinic. And the clinic nurse gets the brief history, and in this particular patient she finds that there was a history of ventricular septal defect that closed on its own. This child has been in the fifth percentile for height and weight historically and currently. Has a history of chronic otitis media, four sets of PE tubes. And then the nurse finishes by saying that the child looks different and doesn't seem to understand personal boundaries. And oftentimes they'll get and they need genetics. So some findings for this case after the clinical nurse specialist evaluation is some dysmorphology. And dysmorphology are simply minor anomalies that don't require usually any type of surgical or medical intervention, but together sometimes it's established a pattern consistent with a syndrome. And so in this trial, you see mildly upward slanting palpigal fezzures, rectangular nose, downward turn, upper lip, which is something that we see in children with hypotonia. Somewhat prominent simplified ears, long slender fingers. But an exam of the palate, there's no palatal notch or bifid mucula suggestive of a submucous cleft palate that might be explaining the hypernasal speech. And I give you a link here on the slide and it's also in the article to a very valuable website that has a lot. It's the 2009 American Journal of Medical Genetics Special Issue, elements of morphology and standard terminology. And all those articles are available for free access. This child also walked at 15 months, single words at two years, full sentences at approximately four years, but difficult to understand. And this child, she also has difficulty following sequential instructions. During a vealopharyngeal insufficiency clinic, a nasopharyngoscopy is done and the findings in this child are a short palate, poor lateral wall movement and medial displaced internal carotid arteries. The short palate, the poor lateral wall movements are suggestive of some hypotonia. And these together make it difficult for the, if you say a K sound, you'll notice that your soft palate goes against the back of your throat or the pharynx. And if it's short or there's poor lateral wall movement, you can't close off that space and air escapes through the nose. The medial displaced internal carotid arteries obviously are an important finding if surgeons are thinking about doing a pharyngeal flap, which is making essentially a muscular bridge between the soft palate and the pharynx. It is also a sign that really increases suspicion for the disorder that I'll talk about. So this is an abbreviated family history and the blue circle is the five-year-old child with hypernasal speech and the VSD. And you can see that mother is healthy, dad is also healthy. There is a maternal grandmother with ovarian cancer. And in clinic, I would investigate this further, but for the purposes of this talk, I'm focusing on BCFS, which is what I'm going to be talking about. So we also, during the history, the father has some hypernasal speech remnants of hypernasal speech in certain things that he says. And with further questioning, the nurse learns that this father also had a cleft palate repaired and he was an average student, but required a lot of tutoring and currently operates a dairy farm that's been in his family for generations. So based on all this information, the clinical specialist orders a fluorescent in situ hybridization test or FISH for a very specific region on a specific chromosome, chromosome 22Q, which is the long arm of the chromosome, and the specific area of 11.2, which can be deleted. And so this FISH picture shows two chromosomes that are highlighted in green. And in this test, a probe is placed and it attaches to a very specific region of chromosome 22 that identifies it as chromosome 22. Another probe attached to a different color fluorescent dye is put in the mix and is specific to the region of interest for chromosome 22. And if that region is there, it sticks to it and if it's not, it doesn't. And so you see that only one chromosome has both colors and the other one does not. And this is a consistent finding and diagnostic of Bela Cardiofacial syndrome. This is a semi-chroscopic chromosome deletion syndrome or more accurate to call it a contiguous gene deletion. There's approximately 40 genes in the region that is typically deleted. It's a three megabase deletion typically. The majority are de novo, but once a person has this deletion, they can transmit it in an autosomal dominant manner. So that brings us back to the family history and I already blew it when I said I was going to talk about BCFS the last time I showed this. But anyway, so because of the cleft palate in the father and his struggles in school, what I would do with this family after discussing the diagnosis of Bela Cardiofacial syndrome would be to present the opportunity to test both parents as this sometimes can be inherited and you can see that they are pregnant and may want to know that information for that purposes. And so with doing another fish analysis of the parents, we find that the father is indeed affected. And so now the focus of the care becomes that pregnancy. And this is when the clinical nurse specialist or nurse involved in this family would call the nurse midwife and talk about the ramifications for this potential pregnancy. And if the clinical nurse specialist and nurse midwife did not feel comfortable doing the genetic counseling for prenatal care, that can be referred to another health care professional that feels comfortable on that. It just really varies when you would do that counseling. You just have to feel competent. So Bela Cardiofacial syndrome is extremely variable in its expression, but it is 100% penetrant. So if you have that some microscopic deletion, you will have some of manifestations of the condition. 70% of people have congenital heart disease or pallet abnormalities, which includes palatal functional abnormalities and structural abnormalities, or characteristic facial features or learning difficulties or immune deficiency or any combination of those characteristics, which are the major characteristics. 25% of adults have psychiatric disorders, typically schizophrenic, but that can start manifesting in adolescence. And then there's a very long list of additional findings that are possible. And on the slide, I have the two links, one to the genetic reference link and the other two gene reviews to learn more about this condition. This condition would make it difficult for prenatal counseling is that variable expressivity, and it can vary dramatically even within families and in identical twins. So again, reason to consult with trustworthy up-to-date resources so you can anticipate the type of health conditions that need to be monitored or the multidisciplinary care you may need to coordinate for patients with this disorder. So I've already alluded to the fact that Bela Cardiofacial syndrome can be identified prenatally if the parent has a condition. Nurse midwives and nurses in OBGYN settings may encounter pregnant women with this condition. Certainly, nurses involved in primary care have a critical role for assuring that related health conditions are regularly monitored and that multidisciplinary specialty care is arranged as needed. Nurses in school settings may encounter children with this disorder. And by using available resources, you can help teachers understand the type of learning problems these children might have or be advocates for assuring that they have the necessary developmental educational testing so they can receive the services in school that they need to reach their maximum potential. Nurses in surgical settings also may encounter children and adults with this disorder because of the craniofacial cardiac and other organ system involvement that could require surgical repair. And also, nurses in research settings may also be involved with trying to learn more about why is there so much variability? What are the aspects of that or how do families cope with this condition? One of the last things I want to talk about is the potential expanding scope of childhood genetic disorders. At the March 2013 annual American College of Medical Genetics meeting, which I did attend in Phoenix, the recommendations were released regarding the reporting of incidental findings in clinical exome and genome sequencing. Just a quick introduction. We think of primary and incidental findings. The indication for the test, why you're doing it. The genetic variant or variants that you might find associated with that genetic disorder or rare disorder would be the primary findings. But because you're looking at the entire exome, which are all the protein coding portions of known and suspected genes in the genome, you also can identify variants in other genes that are known to be associated or causative of other genetic disorders. And so those would be incidental findings. For clinical exome, it's often necessary to compare the child's exome to the parent's exome. So in the process of doing that, you could potentially find incidental findings in one or both parents as well. And what these recommendations are recommending is a list of genes that laboratories should examine and report, regardless of the indication and regardless of the age of the patient. So this includes some of the cancer predisposition genes that up to now in the pediatric world, we have said that the child, when the child is old enough, that the child should have the right to be able to make a decision about whether or not he or she wants testing for some of those predisposition disorders. And also the family history is often relevant to whether or not those tests might be informative. But in this situation, you're going in regardless of family history and looking at these different genes. And so predisposition breast ovarian and colon cancer genes are on the list. And so we have to start wondering if this testing becomes more common, are such predispositions for adult disorders now within the umbrella of childhood genetic disorders? And what's unclear is what we do with that information and how to interpret it, especially if the findings are within a negative family history. So what's really important to me in exome testing and whole genome testing, especially in regards to these recommendations is that this testing be done by healthcare professionals, especially trained in genetics, who can really provide the information necessary for parents to make decisions about whether or not to pursue this testing, knowing that they could potentially learn a lot of other information about their child. And interestingly, these recommendations are specific to the pro-band, the person who comes in. And like I said, these are oftentimes necessary to compare parent DNA. And it is unclear, and I think left to interpretation for the labs on whether or not they need to go back to the parent's genome and specifically look at those genes. What I'm hearing in conversations is there is no intent to do that. So again, more discussion about that. So I list some valuable resources. If you are looking for healthcare professionals, nurses and other healthcare professionals, you have been trained in genetics who can talk about the best types of genetic disorders that can potentially be picked up in exome sequencing or whole genome sequencing with the last one being the clinic directory of genetics clinics, which has both national and international clinics in there, since we are talking potentially to an international audience. I think that's also very useful. And with that, I'll stop. So we'll open it up for questions. Thank you, Cindy, very much. I'll give a few minutes to see if there are any questions. But while we're waiting, just a reminder that the very last webinar for this special issue series will be Tuesday, May 7th from 3.30 to 4.30 p.m. And it will be on the blueprint for genomic nursing science. This is an article that was summarizing suggestions for targeted research to build the evidence base of the value of genomic information. Reserve your webinar seat by going to this last link posted here. And I'll just say, is there any questions for the last minute for Cindy Prouse or for Dr. Johnson? I did see one that we weren't able to answer when Dr. Johnson finished her presentation, so I'll see if you'd like to address this, Nora. Given the recent DSM revisions to come out soon, how will this affect the numbers given current stats? And give me a moment to open up your microphone. Nora, do you want to address that, or Catherine? I think that's a Catherine question if she's still here. Catherine? If she's not though, I... She is. Catherine, any insights? Okay, Nora, go for it. Well, I have... I recently was on a panel, and that question did come up with the DS5 coming out or thought to be coming out shortly. There is some concern that it's going to affect the numbers because there will be one broad category of autism spectrum disorder. There is proponents on both sides saying it's not going to change, and some say it is, so I think it's going to be a wait and see. Thank you. I had two comments from the audience. One says thank you, and the other one says not a question, but thank you all for your time and expertise. There was a lot of good information presented today, and I concur, and with that we will end today. Have a wonderful weekend. Thank you, speakers. Thank you.