 Kathy, would you like to introduce our speakers? Yep. So we're really delighted to begin with the integration of genomics and cancer paper, and the two authors who were predominantly responsible for that paper are joining us today. And the first is Dr. Erica Santos, and she's actually joining us from São Paulo, Brazil, and is currently working at the Hospital AC Carmago in their oncology and hereditary colorectal cancer program there. And in addition to that facility, she's also the supervisor for their graduate program, and she teaches oncology nursing. Erica is very active in the International Society of Nurses and Genetics and is the editor of the newsletter, and she's been the editor for several years now. And then Dr. Debra McDonald is also joining us. She'll speak second in this particular presentation, and since January, Debra's been working with me here at the National Cancer Institute in the Center for Cancer Research in the Genetics Branch. Prior to that, she's had an illustrious career in cancer genetics, first at Massachusetts General Hospital, and then for many years now at the City of Health Comprehensive Cancer Center, in their clinical cancer genetics program that she helped develop there with the team. She's been a longstanding member of ISONG and also was a former president of the International Society of Nurses and Genetics. So I'm going to turn it over to the both of them. Hello to all. My name is Erica Santos. Debra McDonald and I will talk in the next 20 minutes about integration of genomics in cancer care. On behalf of all the authors in this paper, we'd like to thank NIH for this opportunity to talk with you about this issue. Next please. Next slide. So the aim is to introduce how genetics and genomics are integrated into cancer care from prevention to treatment. Next. So the presentation will cover five topics, etiology of cancer, cancer risk assessment, tumor profiling, pharmacogenomics, and target cancer therapy. Next. So we decided to use a cancer study approach. So Mr. J is a 41-years-old European ancestry. His biopsy showed right side column cancer and two polyps. He had no prior cancer history and his medical history was unremarkable. Next. This is Mr. J Pedigree. So we can see here that he had column cancer at age of 41 and two polyps. His father had column cancer at age of 41, 50. His father had, his aunt had uterine cancer at age of 43. And his grandmother had column cancer at age of 52. So we will discuss the implication of his personal cancer history and his familial cancer history later on. But first of all, I would like to talk with you about the etiology of cancer. And cancer is as a genetic disease. Next. So cancer is a genetic disease is multifactorial and infection and chemical products and radiation alters DNA structure. So genetic and genomic factors underlie the etiology of all cancers. Next. So it's important that we know the etiology of cancer and all risk factors that are related to the cancer development because this is important for cancer risk assessment. So there are different risk factors that are related to the cancer development. Nurses must recognize those risk factors and the radiation chemical, biological and one of the important risk factors are genetic susceptibility. Next. So if we, according to cancer history, family history, tumors can be classified as sporadic, familial and hereditary. This has very important implications for the development of strategies for monitoring individuals and also at risk family members. Next. Sporadic tumors account for 75% of all cancers and usually occurs at an age of one set that is expected for this kind of cancer that we are talking about. For example, column cancer at age of 65. They are related to somatic mutations in a specific tissue. For example, breast or column cancer, for example. Next. On the other hand, if sometimes we can see the same time of cancer occurring at the expect age but in more than one close relative on the same side of the family. For example, two siblings with column cancer after the age of 60 or two sisters with breast cancer with age of 65. And sometimes this is referred as familial cancer. And this accounts for 10 to 15% of all cancers. And this is likely the combination of environmental and dynamic influences that are shared by close relatives or low penetrant genes for SNPs. Next. And 5 to 10% of all cancers are hereditary and they are due to a single gene mutation in the germline that predispose an individual to developing certain cancers. The hallmark is an early age at onset that normally the expected for a particular cancer, for example, column cancer at age of 30 or breast cancer at age of 30. And this is, as I said, a germline mutation that is usually related to this kind of cancer. Next. So most germline mutations are transmitted to the offspring by the mother or the father during conception. And somatic mutations, on the other hand, are not transmittable. And they occur into somatic tissues. Next. So how important is to recognize the difference among acquired and heritable genetic mutation? This is very important because it's the key to appropriate referral and further evaluation. And how can we achieve that? Next. One of the tools is cancer risk assessment. Cancer risk assessment is used to define cancer risk for the clients and family members. And this is used through the collection with personal health and family history. Through cancer risk assessment, we can identify individuals who might benefit from genetic and genomic testing. And also we can provide cancer screening strategies for those individuals. And cancer risk assessment is a very important tool to access psychosocial and cultural implications for cancer risk assessment. And one of the most important things is to provide education, counseling, and to facilitate informed decision making. But when we consider the cancer risk assessment, of course, it's not possible to refer all patients to cancer risk assessment. So we need to identify those individuals who should benefit with this strategy. So we have the red flags. So red flags are features on personal or family history of cancer that draw attention to suspect familial or hereditary cancer. So these are the red flags. They are only an indication for investigation. So we have here earlier age of cancer, almost at the expected, same time of cancer or more close relatives, two or more primary cancer in the same person, and the constellation of cancer's characteristic of hereditary syndrome, for example, breast and ovarian cancer, or column and uterine cancer, and some male breast cancer, ovarian cancer, thyroid cancer, and any age, particular, actually, medriary, thyroid cancer, any age, and imitation that in a family. So if we, next, if now we come back to our case, I'll petrify. Next, we can see now if you come back to our case study of the pedigree of Mr. J, we can check some red flags here. So we have age at diagnosis earlier than expected, more than column cancer, three cases of column cancer, which is not expected here. So we have three cases of column cancer. And we have also a constellation of a syndrome, which is ovarian cancer and column cancer, which is characteristic of a syndrome. So based on these characteristics, Mr. J was referred for evaluation and molecular investigation and discuss it with the patient. So now, Deborah will continue with the presentation. Okay, so thank you, Erica. Now, turning to tumor profiling, this is the evaluation of genomic factors, not just individual genes, but the study of one's entire genetic makeup, proteomics, the study of the structure and function of proteins, and epigenetics, or factors that can change the expression of a gene, or the physical, physiologic, or biochemical characteristics of an individual that are not due to a change in the DNA. So here if we take our example of tumor profiling by a process known as immunohistochemistry, or IHC, in Mr. J's case, this test is performed in the pathology lab on tumor tissue to screen for lymph syndrome by examining the protein expression of the four primary mismetry peer genes that are associated with the syndrome. And as you can see, there is very little expression of MLH1 here, protein product, as compared to the expression of the other three genes, suggesting that the MLH1 gene could be mutated. This helps to guide genetic testing by targeting testing to this specific gene, rather than testing for all four genes, and thus it's a more effective and a less costly strategy. So microsatellite instability testing, or MSI, is another laboratory test that when microsatellite instability is found, it suggests that the individual has lymph syndrome. However, about 10 to 15 percent of microsatellite instability is present in various sporadic cancers. So this is a clue, as is IHC, that there could be an underlying genetic susceptibility to colon cancer, specifically here, lymph syndrome. MSI testing requires tumor tissue, as well as non-cancerous tissue, as seen here. We've got the normal tissue and the tumor tissue, and the normal tissue could be that from a surgical specimen or a blood sample. So the tumor is classified as unstable when there are short, repetitive sequences of the DNA base in at least 30 percent of five or more markers analyzed. Here it's shown as repeats of CICACA, or cytosine and adenosine, two of the four chemical bases that make up DNA. MSI testing is also used in early-stage colorectal cancer to guide choice of chemotherapy since microsatellite unstable tumors are resistant to 5FU. This is an example of an algorithm for evaluating a colorectal cancer case. The algorithms such as that updated yearly in the U.S. by the National Comprehensive Cancer Network, the NCCN, are also available to guide genetic and genomic testing. And nowadays it's becoming much more commonplace, at least in the United States, to initiate tumor testing for lymph syndrome with IHC and or MSI at the time of initial diagnosis of a colon cancer. And in a case where there is less suspicion of lymph syndrome, for instance, some institutions might be performing BRAF testing when MLH1 is deficient on IHC. And the BRAF testing can be used to rule out lymph syndrome quickly and less costly than going to genetic testing by sequencing. The common V600E mutation in BRAF is present is evidence of sporadic versus hereditary colorectal cancer. This here shows the DNA sequencing output for Mr. J. As we discussed, his tumor revealed absence of the MLH1 protein, so the next step then is the targeted sequencing of the MLH1 gene. This testing identified a DNA change at position 1975. You can see that the normal sequence, CGA, and arginine was changed to TGA, so a thymine in place of a cytosine resulting in what should have been the amino acid arginine being changed to a stop codon, which terminates translation of the gene. And this particular mutation is a well-known pathogenic mutation in the United States, the United Kingdom, and Finland. Here this shows microarray, which is a means of looking at the DNA expression of multiple genes simultaneously using a chip or other platform. Shown here we use fluorescent dyes to identify gene expression. A commonly used microarray in early stage breast and colon cancers to help in deciding whether or not to undergo chemotherapy is the Oncotype DX test, which gives a score of the likelihood of cancer recurrence. So a low score would indicate a low chance of recurrence and thus that the individual would likely receive little benefit from chemotherapy, whereas a high score would indicate a higher risk of recurrence and greater chemo benefit. Turning to SNPs or single nucleotide polymorphisms, or that is relatively common changes found in a population, here we want to point out that four new SNPs associated with colorectal cancer were identified via microwave analysis, which when taken together with 10 previously identified SNPs may account for about 6% of familial colorectal cancer. Other SNPs have been identified that are associated with prognosis and morbidity. For example, SNPs have been found that are associated with lymphedema and breast cancer, and this knowledge can help nurses to educate women about means to reduce the likelihood or severity of lymphedema. Pharmacogenetics examines how genes influence drug actions, including metabolism response and toxicity or side effects. For example, as much as 20% of drug metabolism has been attributed to the P450-CYP2D6 enzyme, including response to tamoxifen and response to commonly used antidepressants, trade names Prozac and Paxil, which are also sometimes used to decrease hot flashes, so certain variants in CYP2D6 are associated with diminished response to these drugs, and thus the benefit would be nil or suboptimal. Many SNPs have been identified through GWAS or genome-wide association studies, as was discussed by Dr. Yvette Conley in the February 19th webinar. The therapy is another example of personalized medicine based on molecular features of a patient's tumor, so drugs such as Trastuzumab, trade name Herceptin, the first targeted medicine which was approved by the United States Food and Drug Administration in 1998, are used in human epidermal receptor 2 or 2 positive breast cancers to block cancer growth by binding to the receptor site on the breast cancer cells, since the advent of Herceptin bone marrow or stem cell transfer for breast cancers pretty much become obsolete. Bevisizumab or vestin is another monoclonal antibody it's used to inhibit the growth of new blood vessels in several cancers. This slide, which is in our article, shows how different drugs are used based on one's genes and how they influence drug response. So nurses could use this to explain to patients who may wonder why they are not getting the same treatment as someone they know who has the same cancer. Back to Mr. Jay here, tumor testing for microsatellite instability helped guide the choice of chemotherapy and immunohistochemistry helped to determine the specific gene that was involved in his developing colon cancer and this provided very important information for the patient in terms of his current care as well as guiding future cancer surveillance for him since he would need more frequent colonoscopy as well as other tests for the Lynch syndrome associated cancers than with someone without this syndrome. And this also provided important information for determining cancer risk in guiding, screening and early detection strategies for his family as summed up in the next slide including for his sister, his paternal aunt and her adult children and for his own daughter when she reaches adulthood and the age at which she would be at risk and need to have strategies initiated if she carries the same mutation. So in conclusion then, we've given you a glimpse into how genomics is changing cancer care today and as such informed nurses can educate and support patients in how genetics and genomics impacts the continuum of cancer care as well as risk management and the treatment they receive, a table two in our article lists clinical resources to familiarize and keep nurses up to date regarding genetics and genomics and clearly genetics and genomics is changing the way cancer care is practiced and nurses play a key role in helping patients and families understand these new developments and how they impact cancer in many other areas of healthcare. And thank you for listening to our presentation summarizing the article titled integration of genetics and cancer care in the first quarter of 2013 issue of the Journal of Nursing Scholarship dedicated to advances in genomics impacting cancer care and nursing practice. We have a few minutes I believe before Dr. Siebert's presentation on caring for individuals with genetic skin diseases to answer any questions. So I've opened the microphones for Dr. McDonald and Dr. Santos to be able to answer any questions that come up. Did you have a question please type them in? How important do you think that cancer genomics is for the care of cancer patients at this point in time? Either of you want to answer that? Sure. Well I think as we've shown certainly in breast cancer and in colon cancer we didn't give any other examples, but in lung cancer, melanoma, other cancers we're beginning to use personalized care in genomics in guiding the care as we've shown and how patients will respond to certain therapies so that we could change the therapy if the genetic makeup shows that they don't respond to that therapy or in other ways such as that. Erica, did you want to add anything? No I think as we advance we are going to use this even more in our daily practice so every time that we have a patient with cancer we are going to have this more and more and this is our daily, we use this genetic testing in our daily basis at least and in my practice I use this and target therapies is reality of course that I live in Brazil we still have some issues about covering issues as covering and because target therapies are very expensive and sometimes we have this kind of problem and also genetic testing is a problem and sometimes because of insurance so we are having some debates here about that but genetics and genomics is a reality but we are still discussing the coverage issues because it's very important thing to debate also so this is the debate is an ethical debate for us here also so this is a problem. Thank you Erica. The next question is how can we get more education and training regarding SNP and the clinical utility and it says is testing available throughout the country and what are the cost insurance coverage that's available and I think Erica addressed this for Brazil Deborah do you want to say something about it for the United States? Sure, sure well there are certain tests now that are covered by most of the insurers and I think that's as Erica said it's evolving and now we are looking at panels of testing for instance in families where you may suspect there is a hereditary predisposition but not due to the most common genes that we typically test for such as BRCA1 or BRCA2 there are now multi gene panels that look at several genes involved in the development of breast cancer. Insurance coverage for those tests is just beginning to come into play with I think that individual case would probably need to be argued for at this point as to why that might be necessary and perhaps a more cost effective approach than going through analyzing one gene after the next after the next. So we're on the forefront of all of this and in terms of learning more about it I think just keeping up with the literature going to format such as the G3C case presentations that we are working on and have several available already up on the website www.g-c-g-c.org and just keeping up with the literature because this is really evolving area and speaking to your whoever is the person in your area who may be more involved in this practice at the current time advanced practice nursing working in genetics or genetic counselor for instance. Well thank you both very much for a very informative talk and just to reiterate these talks are videotaped and audio taped so they will be recorded and archived on the genome.gov website and at the end of Dr. Cybert's presentation the listing of the website specifically on genome.gov will be provided. So I'm going to open up the microphone for Dr. Calzone to introduce Diane Cybert and as I change the presenter over to Diane she'll be introduced. Thank you very much Erica and Deborah. So I'm delighted to introduce Dr. Diane Cybert. Dr. Cybert is actually a practicing women's health nurse practitioner and she's certified in that capacity as well or current practices at the Walter Reed National Military Medical Center formally known as the National Naval Medical Center. She is a prolific writer and is a professor and director of the Family Nurse Practitioner Program at the Uniform Service Dish University of the Health Sciences here in Bethesda, Maryland. And so she is going to talk to you about the genetics of skin disease. Well good afternoon everyone I'm delighted to be part of this part of this group it's been fun to listen to the talks over the last few weeks and I'm glad to be part of this little this edition for the Journal of Nursing Scholarship. I am as Kathy said a women's health and adult nurse practitioner so the geno dermatoses the genetics of skin disease wasn't something that I was all that familiar with until a couple years ago when I partnered with Tom Darling my co-author on this paper and he and I published an article in the Annals of Internal Medicine with an interesting population of his over at NIH women adult women with tuberous sclerosis who did not seem to have the classic TSC triad of features of facial angio fibromas seizure disorder and mental retardation and those pictures on this particular slide show various features of this particular skin and inherited skin disease. And so I became interested in this topic and I realized I hadn't really read a whole lot about the genome dermatoses in the nursing literature so I thought that I would like to tackle this topic. So I'll take you with me on a journey as I kind of tried to figure out how to bring this topic to a larger audience. So physical psychological and ethical issues in caring for individuals with genetic skin disease is what I decided to call this paper. So just a bit of background the skin is of course the first line of defense between our internal and external environments and if you have healthy skin it guards against pathogen invasion protects against water loss it helps you regulate your temperature you feel sensations it's part of our haptic sensation in terms of balance and and it helps us synthesize vitamins there's been some really interesting work done related to maternal vitamin D exposure and type for example type 1 diabetes development in an offspring so it's very interesting things related to skin. So the genome dermatoses which in fact was a word I didn't really know anything I didn't know that word existed until about a year ago these are mutations that alter the way normal skin works. Interestingly and probably one of the things that Dr. Darling my co-author said when I first approached him about helping me or co-authoring this paper with me he said you know genotermatosis are interesting in when you think of all genetic disease and that this particular set of mutations don't normally shorten lifespan not there are some of them that do but most of them do not affect lifespan but they have significant impacts on social quality of life and social stigma because of the the skin is so visible to others and managing these dual disorders can be very complex you first have to treat what's happening on the skin you have to educate the patients and their families about this disease but you also have to address the stigma and again this is there's many places where nurses play roles in this if you think about all of these pieces and parts you need to treat and screen for the non-skin manifestations as I said you know when I was talking about tuberous sclerosis complex it's the facial angio fibromas which are the skin pieces but the seizure disorder and mental cognitive impacts are significant for these diseases but recognize that there's lung tumors and also renal tumors as well so the population that Tom and I were working with NIH that we wrote the paper on were adult women who had had very they had the disease but it was not not very expressive in them for whatever reason and they were they had transitioned into adulthood without a diagnosis and many of them had very severe pulmonary disease and were at high risk for lethal rupture of renal tumors so the the recognition of the skin manifestations they lead to lead you to a more potentially more important diagnosis of some internal structural problem that you can help prevent a bad outcome. We also need to make appropriate referrals and that can be complicated in these disorders because again there are several variety of organ systems that may be involved so they may require a team approach or several different referrals to different people. When managing these diseases the roadblocks are pretty pretty common and until recently deciding what the actual diagnosis was was rather difficult and well as we go into the talk a little bit further you'll see I'll get highlights and examples of that. There were very few effective treatments for some of these disorders there wasn't much research particularly in a rather rare some of these rare recessive disorders and as a result and because they're rare there are a few other affected people in your community that you could talk to and with the advent of the internet that's changing pretty dramatically in helping this population of patients too. So diagnosis of these some of these rare conditions is now possible that we have gene sequencing and we know what genes to look for the internet is as I kind of mentioned people are able to look outside their communities and local communities for people that might also have these relatively rare disorders and the internet is helping them find support groups and here are several that I that I ran into as I was putting together this paper talk against genodermatosis very powerful really robust sites, psoriasis, albinism incontinence, chepigmatae and an eczema support group so just an example lots of things happening out there on the internet now. So a little bit about the genetics I was stunned really to realize that there are over 500 genetic mutations that look like they cause somewhere in the neighborhood of 560 or 70 distinct skin disorders 400 of which can be traced to a specific gene but it's interesting because there's significant overlap between the disorders in terms of how they manifest on the skin so categorizing has been rather a nightmare and if you go back into history and look at textbooks of skin diseases you'll find authors you know here's a dry skin disorder to be left with these other dry skin disorders and so lots of confusion in the community about what categorize you know what category these disorders belong in but as we have become better understand the physiology and path of physiology of these skin diseases and the genetics of these diseases they're settling on the genetic the dermatology community has begun settling on classification systems and there are about 12 of these categories based on the type of skin lesion and then they are further subdivided based on their inheritance pattern. Some of these disorders may surprise you osteogenesis imperfecta I think most of us recognize that as a fracture bony fracture but there are also skin manifestations with that. Cowden's syndrome is considered a cancer syndrome but there are skin features specifically with that hypertrecholoceridemias okay that's cholesterol but skin shows up there and hemochromatosis, iron overload again there are skin features for all of these diseases and so sometimes just highlighting or having clinicians recognize the met the external manifestations get you faster to a diagnosis for some of these. Basically every inheritance pattern is represented in the genodermatosis with their autosomal dominant ones, recessive ones there's x-linked both dominant and recessive there's mosaic there are complex conditions lots of those where there's several genes plus an environmental trigger and then or an environmental a chronic environmental insults and then there's significant heterogeneity as well modifier genes are playing a role here for some of these and it's certainly environmental factors exposure to sunlight dry dry climates or human climates etc. So I the chapter is divided into you know I was working with inheritance patterns and here's the complex disorders I started there because it was the most common things atopic dermatitis and psoriasis. So about 15 percent of kids living in industrialized countries have atopic dermatitis that's a pretty high number and you realize that I put that word industrialized countries in there that's an environmental exposure that seems to be triggering some of this skin disease. Symptoms most people usually have symptoms that manifest in childhood and maybe make them absolutely miserable hospitalized etc. But many of them, many of these individuals get better as they as they age so the skin seems to become a little bit different with age. The mutations appear to be largely centered in this filigren gene there are four other genes that they're working with as well the mutation appears to cause an abnormal enzyme which prematurely disables these corneodecimones and that causes an impaired barrier skin. So things like irritants soap detergents etc. damage this fragile skin it's not built very well the allergens can get in and then you have this inflammatory cascade. So atopic dermatitis really is a model for the gene environment interaction and highlights the differences in expressivity because not all severely affected people have these flg mutations and not all people with flg mutations develop enzyme. So and then this whole idea that the older you get the less disease you have is interested complex process too. The next one I thought I'd talk about this psoriasis about up to 10% of people worldwide and you notice that there's no industrial piece in here so it seems that there's less of a role with industrialized communities or or chemicals perhaps playing a role here this is an autoimmune T cell disorder there's an environmental trigger and a genetic susceptibility so both of these two pieces have to be present. The symptoms very widely between people and it's different than the atopic dermatitis and that in psoriasis there's a very rapid skin maturation so the skin cells don't have this very nice paste growth they accelerate the growth rapidly the cells pile up on top of each other that the immune the immune system is not happy with that big callus type formation and so the immune system comes in to clean that up. So when you have very severe psoriasis and many of you may have seen patients with really it's on the sort of the external surface areas atopic dermatitis tends to be in folds and bends and psoriasis tends to be on external the outsides of elbows and knees that kind of stuff and the severe disease they've done some studies to show that quality of life scores for these patients similar to that of patients with other chronic diseases like hypertension and depression and CHF and type 2 diabetes so this can be a very debilitating disease. There's candidate genes but recognize that these genes are not necessarily skin as skin genes these are immune genes like that you'll find in the HLA complex of genes particularly HLA this particular one HLA CW those six oh two and then interleukin genes seem to be involved these guys are also involved in immune modulation so this is an immune mutation disorder interesting so here are some of the monogenic or single gene disorders that I thought were prevalent enough and interesting enough that that you might see them or be a kind of the interest or their markers for model disorders I guess for other skin diseases so the autosomal dominant one I thought I'd talk about is putziagres then a recessive will talk about albinism and then we'll talk about one x-linked disorder, contention pigment so putziagres or PJs is an autosomal dominant cancer syndrome that picture up there shows you some of the skin findings inside someone's mouth the it's the stick an LKB1 tumor suppressor gene if that gene is broken their life this individual's lifetime risk for developing cancers is very very high 93% in childhood these individuals often have skin lesions these dark blue or brown macules on fingers faces perennial areas if you see these in any of your patients in childhood you need to begin cancer screening or should at least consider this putziagres diagnosis it also comes at because it is a cancer syndrome this is a tumor suppressor gene that's broken you'll see some other manifestations hamartometis gastrointestinal polyps stomach small intestine large bowel nasal passages albeit although these are rarely cancerous they do get large and they do bleed so anemia is a possibility as well as bowel obstruction and intestine seption and usually younger children and then epithelio cancers colorectal gastric pancreatic breast and ovarian so this is a pretty serious mutation and that if the skin can be the first thing that someone recognizes and starts early screening and intervention you may have really gone a long way to improve someone's overall survival and quality of life the genetics are as I mentioned it was in this this stick 11 and LKB1 genes but the still not really clear how this genetics all works with putziagres because there are a number of de novo mutations and it appears to be also heterogenic where multiple genes are involved so not everyone has the same genetic they may look phenotypically the same but they don't have the same genetic picture so when you find somebody has a clinical feature as you counsel as you would for other osteomal dominant disorders and tell the family that the inheritance risk is about 50 percent and that if the mutation is known prenatal testing is available for putziagres albinism it's an autosomal recessive disorder and it involves melanin defects either the synthesis and or the transport of melanin in the skin in the incidence around the world is about one in 17,000 individuals but there's pockets around the globe where the incidence is much higher than that in sub-saharan Africa one in 4,000 Zimbabweans and almost one in 1400 Tanzanians so these communities have a lot of consanguinity a lot of intermarriages or even close marriages across neighboring communities and maybe not very much awareness of how this is actually inherited the most prevalent form is this ocular cutaneous albinism or OCA and there's four sub types and it depends on how what the mutations are like and if they're completely broken and make no melanin at all or whether they produce still a little bit of melanin really really kind of drives how this patient is going to appear externally and how many manifestations they're going to have because melanin is interesting it's critical not only for the skin color but it's also important for eye development obviously you can see the picture on the top right a lot of solar damage so skin cancer is very common in this population and the eye it's not only just the fact that there's no pigment in the eye but also eye muscles so they have poor eye movement poor visual acuity and these children also then have difficulty reading and chat and school challenges they not only look different now they actually have some some intellectual not not cognitively challenged but acquiring information is difficult they have again high prevalence of skin cancer and that that in this in this culture in the united states it may not be so unusual to see little kids at the beach or in the long sleep things now they're starting to do a lot of that but in in sub-saharan africa it would be pretty unusual and probably these people would be a bit shunt if they start wearing long sleeves and hats and things they need to protect their skin so social stigma for these for these children in particular can be very very profound they have very pale skin pink eyes they struggle in school they often stay inside they wear unusual clothes in the clothing and this is an extreme example of a social stigma but in some South African albino communities there are body hunters that are actually looking for albino people they kill them or they dismember them and make their body parts into good luck charms so very scary these communities that there are children that actually flee to this quote unquote safety of larger anonymous urban communities trying to to stay alive basically which increases their isolation and their marginalization so this is a big a big problem and so again it's that the the skin mutation if you can protect their skin and help them with their learning needs it doesn't really affect longevity but if the social stigma is so severe that they have to find themselves in a lonely community isolated it can be a very debilitating disease incontinentia pigmenta is a very rare disorder it's excellent dominant what's interesting about this is I really learned more about excellent most of the excellent disorders that I had really thought about before were really recessive disorders this one is dominant so if you have one mutation you're affected and so that means that girls are affected if you are a male and you only have one x and that one happens to be affected you usually don't get out of embryogenesis here or your if you make it to term pregnancy you often die very early in your life so the people affected by incontinentia pigmenta are women there's only about 700 women around the world it's because it's lethal and virtually all men you're not going to see it in boys the diagnosis is interesting because again it's it's a clinical diagnosis confirmed by skin biopsy or now by gene testing and the expression varies really widely they have this very interesting development of skin lesions from birth into adulthood they have this very severe blistering and that's this picture that I put up here just really represent some of the pictures if you go to a google images and do a search on this you'll see some severe skin manifestations but blistering till about four months of age then this wart like rash that appears for several months then they have hyperpigmentation for the rest of their lives and they have these very interesting brown and slate gray lines wavy lines again you'll see some of those if you go do a google search on it and then they also have very interesting other features like the alopecia strange teeth formation of teeth dystrophic nails cataracts so again more eye features retinal detachment severe vision loss again cognitive delay and intellectual disability and then some some various potentially really severe skeletal abnormalities hemivirtebrae scoliosis spina bifida syndacty and a congenital absence of the hands all of which caused by an excellent mutation so what's the role of nursing hopefully as as I went through this kind of again quickly you could think of ways in which you might interact with some of these patients we are basically everywhere in healthcare we're engaged with people in virtually every life event from birth to death to every place in between we're present in all healthcare settings we work with all populations and the public expects us to understand how genetic conditions are inherited again those communities in Africa that need more education about albinism they need they expect us to understand how common conditions are inherited including things like skin diseases like atopic dermatitis they want us to help them navigate some of the social and ethical issues recognizing that children with albinism have visual challenges as well as and helping them access those resources just understanding the relationship between the the eyes and social outcomes is important they also expect us to help them navigate some of these physical and emotional and social consequences of some of the disorders that they they have they want us to help them get access to some reputable resources there's lots of stuff on the internet and again as I was searching around looking for things to bring to you you run into interesting and very unhelpful or misleading pieces of information they want this stuff rapidly so that your your being facile with the computer really helps your patients and then offering suggestions about coping how to cope with some of the some of the funny looks or the fact that no one will shake your hand or laugh at you at the way your that your hair or eyes are colored etc so our job in terms of pairing nurses my job here at the university is to be aware of what it is that that nurses need to know and I think hopefully all of you are familiar with the two guidelines now that have been published related to what all nurses need to know the essentials of genetic enjoyment nursing competencies with the outcome indicators from 2008 and then the new essential and genetic general competencies for nurses to prepare at the graduate level that was published last year so in conclusion really nurses need to be familiar with the germic geno dermatoses more commonly seen in your communities need to be prepared to develop individualized care plans for patients and families with genetic concerns and be able to discuss the ethical issues that surround genetic testing which includes incidental findings there's been some new work ACMG released a new paper recently about how to an approach at least incidental findings so skin diseases affect millions around the world it's accompanied by significant morbidity which includes quality of life issues social stigma isolation it's we're still learning about the genome dermatoses many people don't understand them very well the ethical legal and social implications are similar to those patients that have other genetic diseases including all the issues around genetic testing and nurses are important because we can link the science of genetics with the human experience of health and illness and we can make an important positive difference in the lives of our patients of all of our patients but in this context patients with hereditary scan disease so um I think I will stop there and see if there are any questions or comments hopefully I can answer something like I said I'm not a particular expert so Diane there was a question um from an attendee who says I had a patient with a sclerosis fibroma of the nose the dermatologist recommended p10 testing is this lesion part of the p10 spectrum that is a good question and I don't have a good answer for that I would have to I'd have to do a literature search to find that answer myself I don't know if Deborah or Erica or you're either you or Kathy have an answer for that so I've opened up the microphones does anybody else want to address the p10 discussion about the fibrosis of the nose what was it in the nose I didn't quite get it let me read it it says fibroma a sclerosed fibroma of the nose and the dermatologist recommended p10 testing is this lesion part of the p10 spectrum well there are um sporadic fibromas that can be seen in carbon syndrome so um it it could be a cutaneous marker of the disease uh I've not come across it myself so I'd have to do a little more I'd have to look look it up a bit and see if it if it actually meets criteria for testing but but it is a marker of uh that has been found in Calvin's disease before so Dr. Calzone you want to tell them a little bit about the PDQ database where some of this information might be located so PDQ at cancer.gov actually maintains evidence-based reviews of hereditary cancer syndromes and other associated variables if you go to cancer.gov you can look at an individual topic and in um Houdens for example it falls under the genetics of breast and ovarian cancer because it's a syndrome that is associated with breast cancer as well as other cancers um and when you click on breast cancer at cancer.gov you just scroll down to the genetic section and there'll be a whole section on the current evidence associated with Caldons and the clinical criteria associated with the um you know indications for testing for uh mutations in P10. Thank you um any other questions that people want to submit go ahead and do so and um Diane could you move to the next slide which also shows the next webinar coming up if you have that available so while we wait for the last few questions um just a reminder that the next webinar is April 26th and it will be on autism as well as an update of childhood genetic disorders so if you have colleagues that are interested in pediatric conditions um please tell them about how to register for this webinar for April 26th so I don't see any other questions so I'm going to open up the microphones to our presenters just to have one last word before we close out the day. Deborah any other parting comments? Well actually I did have a question um Diane that was an excellent presentation thank you so much and um I certainly learned a lot. I have a question about Pute Shaker testing I think you mentioned that there was prenatal testing available and how would this be uh useful or is there some intervention that would be initiated that would um uh justify prenatal testing or is this something where people might even choose to terminate? Well that's a really good question I think that that comes up with a lot of the more the more we know about um genetics the more the attempting it is to do things uh preconceptually or conceptually so if you know what the family mutation is of course you can screen for it you could do it pregestationally with a PGD pregestational diagnostic testing or you could test for it prenatally that's a discussion that that again these patients should in my view these conversations should occur prior to conception certainly um what are you going to do with this information um but the fact the fact is that it would that it does exist and so um hopefully you're not first diagnosing something like a cancer syndrome in um early in pregnancy and have to then make a decision about whether you're going to do prenatal testing ideally you do that before you ever got pregnant and it's going to it's going to raise it's going to raise a lot of issues over the next decade or so the cell-free DNA even increases potentially increases the sensitivity decreasing the risk for normal fetuses too Erica any last comment well thank you for joining us from Brazil and I know that is very difficult to make sure all these connections work so thank you and Kathy any last comments no none here we hope that you'll join us and for the next set of webinars that's coming up at the end of the month so thank you Diane and Debra and Erica any other comment Diane no I don't think so I enjoyed it thank you I think it was a good pairing of these two talks together I appreciated the I really had learned a lot from the cancer one too so thank you thank you very much this is Debra so I'd just like to say that you know I think that we're we're in a very rapidly developing ELA that is changing healthcare quite dramatically and will continue to do so so that webinars and publications such as in the Journal of Nursing Scholarship um are really necessary for nurses to be kept current about what's what's going on in these awareness and and to be able to not only use this information with their own patients and families but also in even with other healthcare providers including physicians and others who may not be aware of the latest developments well thank you all and have a wonderful afternoon thanks