Genetic testing and early intervention can have benefits ranging from preserving vision – as in the case of retinoblastoma – to preserving lives. But do they bring anxiety or peace of mind? Offering evidence for the value of diagnosing hereditary cancer syndromes, pediatric hematologist-oncologist Jennifer Michlitsch, MD, discusses how to identify patients at risk, take informative family histories, and ensure care reflects the needs and values of individual families.
I'm john McClain from one of the pediatric hematologist oncologist. Um I am mostly based in the East Bay but also do a lot of a joint collaborations with the West Bay folks as well. So I'm going to be talking today about cancer predisposition syndromes. Um uh for the past couple years I've been a part of the pediatric hereditary cancer clinic which is a joint East and West, a comprehensive service that we offer um to Children and really whole families who may be affected by cancer predisposition syndromes. I wanted to introduce that clinic um and our program to you today and sort of talk a little bit about cancer predisposition syndromes um and how to look for them and uh what surveillance we may recommend. Okay. Mhm mm. And now it is not letting me advance. Okay, there we go. So just a quick agenda today, I'm just an overview of hereditary cancer predisposition syndromes. I'm going to talk a little bit about the key elements and taking a cancer family history. Um some of the consequences, both medical and emotional and social of being diagnosed with the cancer predisposition syndrome. Um and then I'm gonna highlight just a few of the more common syndromes that we see specifically in Children and that could affect Children. Talk a little bit about the clinical features the genetics involved and some of the surveillance recommendations. And then finally I'll go over how to refer a patient or family to our clinic. So just to start off with a key study. Um So you're seeing a new patient in your office who recently moved to the bay area. This is a 16 year old female and her medical history is significant for a diagnosis of localized osteosarcoma of the distal femur. When she was 13 years of age, she was treated with chemotherapy and a surgical resection, including a limb salvage procedure and is currently in the clinical remission and doing quite well. Overall, family requests a referral to the oncology program at Children's Hospital for ongoing surveillance scans and monitoring for late effects of therapy. She and her mother happened to be quite tearful that day and they report that the patient's father was just recently diagnosed with a brain tumor. And so this is your first time meeting the patient and the family. So you take a thorough family history and you learn that this is significant for an aunt with breast cancer and a grandfather who died of stomach cancer. And the family asks you whether the patient herself, maybe at a higher risk for future cancers and what if anything can be done. So I think everyone is probably thinking now that there should be a pretty high suspicion in this case for hereditary cancer syndromes. And this is really defined as an inherited disorder in which there is a higher than normal risk of certain types of cancer. Um It's known by some other names, including a family cancer syndrome or inherited cancer syndrome. Um and these are caused by mutations in certain genes that are passed on from parents to Children, mutations can be either dominant or recessive. Um And they can cause early onset or late onset disease. And I'll go over a cover a couple of examples. Um There are certain kind of classic patterns of cancer that can be seen including several close family members with the same type of cancer. Uh Family members developing cancer at an early age um And two or more types of cancer within the same person. And it has been well shown now that genetic testing and early intervention can in fact improve the chances of detecting um and treating cancer in its early stages and can actually affect the likelihood of overall survival. So just a little bit about taking a cancer family history and I'm sure this is something that you're already doing. I know that many offices do a paper intake form initially which is great. Um But just to review this um briefly this is something that really should be taken at the patients first visit and then periodically updated and really what you want to ask about is not only the patient but all first degree relatives. So siblings parents and then also Children if applicable. Um And then also secondary relatives. So grandparents, aunts and uncles, grandchildren, nieces and nephews and hop siblings. You want to ask about specifically both the maternal and paternal sides um when known. Um It's also important to ask about whether there is any Ashkenazi ancestry because there are certain cancer predisposition genes that are seen more commonly in this patient population, including mutations in the BRCA gene um for each family member that has had cancer, it's important to establish how old they were at the cancer diagnosis and oftentimes family members won't know for sure, but you can asked whether it was under age 40 over age 40 etcetera. Um and then the type of primary cancer when known, We know that cancer genetics are becoming increasingly integrated into medical oncology and that up to 10% of all cancers are known to develop an individuals who do carry an inherited genetic mutation that confers susceptibility to specific cancers. And so the American society of clinical and oncology or Asco actually has developed really helpful guidelines which have been revised a number of times as you can see and they also have come quite helpful education materials both for oncologists and families. Right. It's important and this is something I think that we're learning more and more about to really consider the whole spectrum of consequences when a family is faced with a potential cancer predisposition syndrome. And um there are of course a whole variety of implications of a positive test result for mutation carriers um that beyond extend beyond just the immediate cancer risk. Um so often times people will will worry that they may pass on this mutation to future Children. Um One concern that is a real concern is that when jeans are tested, um we are sometimes we get a positive result. Sometimes we get a negative result but there are also situations in which we find a variant of unknown significance, which is abbreviated the US on genetic screening results. And that can be anxiety provoking as well because sometimes these are novel mutations or aberrations and there may or may not be much data about whether this specific mutation encourage a higher risk of future cancers. It's important to think about sort of what are the medical options for surveillance and cancer prevention for those individuals who do have a positive test. And then of course the risks of psychological distress and family disruption. And I definitely have a number of patients and patients, families who have declined testing for for such genetic mutations. Um and typically it's because they cite not wanting to know and that they worry that it will just cause fear and anxiety which they're really not prepared to handle. And so one of the important things that we always talk about before we send this type of screening is really kind of walking through some of the psychological ramifications of positive and negative test results in making sure that the family has the resources to be supported by not only genetic counseling but therapist is needed as well. Um many families will bring up a concern about employment um and or insurance discrimination and that's that's a real fear. There are laws in place to mandate against discrimination based on the finding of a genetic cancer syndrome. But of course there's no way to guarantee that these laws will always remain in place. And then of course, um it's important to consider the costs of the testing and the cost of preventative procedures, which often include blood tests or imaging studies. And depending on the insurance status of the patient, this may be some out of pocket expenses to the family. This is a busy table and certainly not meant to be memorized, but it just is to show that there's actually guidelines. Um as far as the elements of informed consent for cancer genetic testing. And so we do require consent from family members, parents and or patients when applicable before sending this type of testing because there are so many implications. And specifically with germline testing. And uh we when I have patients with high risk cancers, we will often offer somatic mutation analysis of the tumor that is paired with the germline testing. But we do get families the option to be given the results of germline testing or not be given. And some families do opt out of the germline results. So this was an interesting paper that came out fairly recently that actually looked at adolescents who have been diagnosed with hereditary predisposition syndromes. and uh it consisted of semi structured interviews with adolescents aged 14 to 17 Years old. And these patients represented six different hereditary tumour predisposition syndromes. And the aim of this was to really find out how our adolescents handling um such diagnoses because this is a formative age when there's a lot of stress going on just in general. Um and really three major themes emerged from these interviews. One being the benefit of uh knowing and the knowledge that that outweigh the harms. Another was that the really that the context surrounding genetic testing must be recognized. And then a third um was that really on the whole, these adolescents felt that their self concept was influenced but not not defined by tumor risk, which is also important. Um and they were able to come up with some strategies to help guide pre test and post test genetic counseling in order to facilitate um incorporation of genetic information into an adolescent self concept. So I wanted to um go over now another case study. This is an actual patient of mine, He is now 24 years of age when he was an infant or toddler in Mexico at the time, he was diagnosed with retinoblastoma of the left eye and I put that he was two years of age at diagnosis that's based on the family's recollection and some scant records. He was treated with a new creation of the eye um and unfortunately experienced a local and a distant metastatic recurrence within the bone marrow, which is a rare sight of metastasis for retinoblastoma, but it does occur, he then received chemotherapy. His family then moved to this country and when he was 12 years old, he presented um to Children's hospital Oakland with chief complaint of leg pain. Um He was ultimately diagnosed with a high grade osteosarcoma of the distal femur as well as pulmonary metastases. Um This was treated with chemotherapy and then surgical resection. He did require an amputation to the extent of his tumor, fortunately he had an excellent response to therapy and he remains in remission at this time. Six years after that diagnosis, he presented for routine follow up and was noted to have a painless mass at his left wrist. Um and then this was imaged and biopsied and he was diagnosed with a lie oh my! Oh sarcoma, fortunately this tumor was localized. Had not spread to lungs or elsewhere. And this was treated with a wide surgical resection to achieve negative margins. He then one year later presented again with a painless chest mass. This was kind of uh in the anterior chest wall and this was respected and was fortunately consistent with an angio like poma. Um and he now I continue to see him. He has had a soft tissue mass at the base of his left neck. It has been stable in size for the past couple of years. We have gotten a couple different ultrasounds and it looks to be consistent with most likely a like coma. He has not wanted to have this biopsy or respected. Okay, so um as you may have already been thinking, this is a case of hereditary retinoblastoma. Um I should say just to go back when I'm at the station for his osteosarcoma diagnosis. We did suspect that he may well have an underlying cancer syndrome based on the history of retinoblastoma and then the development of osteosarcoma. And so we did do germline testing and Did confirm that he carries a mutation in the RV one gene. Mhm. Um hereditary retinoblastoma is kind of the classic hereditary cancer syndrome. And one of the first described actually retinoblastoma is Doly rare even among pediatric oncology cases, there's only about 200 cases per year in this country um can present as a unilateral or bilateral tumor. Uh bilateral tumors typically present a little bit younger. The median age of presentation is at eight months and these cases are most often hereditary in nature. The R. B. When gene was actually cloned in the mid 1980s and was found to be the first identified cancer. Susceptibility gene, its function in the normal state is as a tumor suppressor. And so when this gene is mutated patients are at increased risk of developing tumors or cancers. And this is sort of uh felt to follow the classic what's called the Hudson model of cancer predisposition, which consists of the two hit model of neurogenesis. And so if there's a mutation in one gene, um there's still a remaining jean it's normal But if that remaining gene takes a hit um it becomes non functional. That's when you can see uncontrolled cell growth leading to a tumor. Um It's important to diagnose these cases early as early as possible because the therapeutic options actually really depend on the extent of disease. Typically, if these cases are diagnosed early, it is the most often possible to preserve both eyes, which is important long term. Um in addition to the retinoblastoma, we also see a number of common uh second primary tumors and new patients with journal in RB mutations, including very often osteosarcoma, malignant melanomas can be seen several types of brain tumors, breast cancers, especially at an early age and leukemias. The median age of a second primary tumor is in the teenage years. So 15 to 17 years. So this patient was right around, right around that At the time of his presentation for a second cancer. The cumulative mortality from 2nd me applause. Ums At 40 year follow up is actually significantly higher in patients who have received radiation therapy, about 30% in patients that did receive radiation versus about 6% of patients that did not receive radiation. So, in addition to screening for early detection, uh knowing about an underlying genetic mutation in the RV when jean would would have an impact on therapy. In many cases with the avoidance of radiation as much as possible. This is just a guidelines for a surveillance protocol for a patient with a hereditary RB one gene mutation. And so, um at the initial stages, it consists of very frequent surveillance for intraocular retinoblastoma. And so you can see here that there's exams um initially every couple of weeks, um and then spaces out to every couple of months. And that's an example under anesthesia for the first several years of life. And then at age five converts to non state exams as possible. In every six months, recommendations are also to survey for what we call trilateral trilateral retinoblastoma, which includes not only both eyes involved, but also a cNS tumor within the brain, usually within the pineal gland. Um and that consists of a brain MRI at the time of diagnosis. Um And then some centers also recommended brain MRI every six months until the age of five years. And then regarding surveillance for 2nd primary tumors. Um Most important is really education about the risk of second primary tumors and then very close attention to any new signs or symptoms. Um It's important to do a thorough skin exam during well, child visits. Um and then to continue these annually by either the primary care physician or a dermatologist as needed to look for melanoma Starting at age 18. Um and we recommend thorough skin exams even before that age. Um, there are some who actually consider performing a whole body MRI uh annually after the age of eight, but this is actually one of the syndromes in which there really is no established consensus. And so our practices generally to talk to families, educate parents about the possibility of whole body MRI and sort of weigh the pros and cons and let the family be a part of that decision making process. A couple other more common hereditary cancer syndromes and pediatrics that I wanted to touch on include lee from amy syndrome, P. 10 Hammer Toma, tumor syndrome, dicer one syndrome, and then hereditary leo, my own mitosis and renal cell cancer syndrome. So, um, you may have guessed from my last slide that these are actually represents dr lee and dr from many Who were the two physicians that discovered um, the what we now know is we've from any syndrome. Really interesting story. I just wanted to give a little bit of historical background on this. So, this syndrome was actually first described way back in 1969 by doctors, Frederick Lee and Dr. Joseph from any junior and really was based on a clinical observation that they made that they noticed a really unique spectrum of cancers in four families in which the index case was a child with rhabdomyolysis or coma. And um looking at the cancers that developed within family members, these were quite diverse neoclassicism consisting of many cases of breast cancer, as well as soft tissue sarcomas. And so what they did is they actually set up a prospective study to look at these four families and study them for the incidence of cancer diagnosis prospectively. And this was done over A several year period between 1960 19, 1981. What they found was that 10 of 31 living family members did in fact develop 16 new cancers and that was Significcle higher than what what would have been expected just on a population basis standpoint of .5 new cancers in this, um, in this family group. And these included five cases of breast cancer for soft tissue sarcoma is two gliomas, Wilms tumor, lung cancer, a cancer of the larynx and then some prostate cancers. And this was an important diagram from their paper published in Jama in 1982. And this shows really. So these arrows here are the pro band. So these are, remember the Children who were diagnosed with wrapped in like a Sarcoma. And then you can see that following up to the parents and grandparents and in some cases even great grandparents that you can see the development of different types of cancers and the types of cancers are down here in these little uh boxes. And so obviously a much higher incidence of cancer in these family members. And um, that form the basis of really growing to understand what we now know as lead from any syndrome. And so this this syndrome really encompasses a wide variety of us as I mentioned, including brain tumors, specifically coronary carcinomas of the court brief Lexus medalla blast oma, specifically on a subtype called sonic hedgehog. Um in in gliomas, adrenal cortical carcinomas, soft tissues are chromosome bones are comas, mental logic malignancies, breast cancers, which is typically early onset, so young age. Um, and then other cancer types as well. Mhm. Lee from any syndrome is associated with a very aggressive genotype. It's a high risk of developing cancers and they tend to develop in younger individuals early onset. Um in another study that was done at 415 mutation cares. And the TP 53 gene, which is the gene involved only from any syndrome, 78% of these carriers developed at least one malignancy. Um, and you can see the breakdown by age here. So 4% of these developed cancer by age 1, 22% by the age of five years and then 41% by the age of 18 years. So definitely on impacts pediatric patients. Um, in Children adolescents, specifically with the, from any syndrome, osteosarcoma is the most common cancer diagnosed, Um, and then adrenal cortical adrenal cortical carcinoma, followed by brain tumors and other soft tissue Sarcomas. Another series through the National Cancer Institute looked at the cumulative accumulative cancer incidents and found that 50% of females only from any syndrome developed a cancer by age 31 And 50% of males by age 46 and nearly 100% of these patients by age 70 years. Um, in the early 19 nineties is when it was discovered that it was actually the TP 53 tumor suppressor gene that was involved in this syndrome. Um And germline mutations in this gene were discovered to be the cause of lee from any syndrome. Um This is a transcription factors triggered as a protective cellular mechanism against stressors. There are many, many t. v. 53 German alterations reported over 250 and the list is growing every day. There's also been a number of genetic modifiers that have been discovered to influence the genotype um including Polymorphism in a gene called MDM two telomere length and others. And so it is really difficult and sometimes impossible to be able to tell a family member what their disease course will look like even if they have the same mutation as another family member. Yeah. Um there is a list of criteria called the Shampoo criteria that describes clinical situations in which mutation testing of TP 53 gene and genetic counseling should be strongly considered and offered. Now listed those here. So the first is a familial presentation. This is when you have a pro band who has a tumor considered a leave from any Syndrome, spectrum tumor before the age of 46 and then at least one first or second degree relative with a leaf from any tumor. The second situation is when you have a program with multiple malignant cities of which at least two belong to the spectrum of leave from any cancers diagnosed before the age of 46 years. any patient who has a rare tumor diagnosed and that includes patients with adrenal, cortical carcinoma, Roy plexus carcinoma or and brian in a plastic subtype wrapped in my a sarcoma. That's a specific subtype of rob thomas sarcoma, which is a soft tissue sarcoma um and really independent of family history And then any patient or family member who develops breast cancer before the age of 31 years. This I think is some really encouraging data. Um, and so the question comes up often. Well, if we know about this mutation, does screening for cancers really change the course of these patients lives? Can we actually impact there the chances of cure and survival? And so this was a study gun based out of Toronto That perspectively followed Children and adult patients who had a TV 53 mutation and they followed these individuals over the course of 11 years. Um, they recommended certain surveillance studies and they actually were able to document that the compliance with the key components of the surveillance protocol Was very good was actually over 90% in those patients who decided that they wanted to undergo surveillance. And um What they found was that patients who were on surveillance had a total of 40 tumors detected In 1959 patients with a median follow up period of 32 months And 25 of those 40 tumors were actually low grade or pre malignant at the time of detection. This was in contrast to patients not on surveillance in whom 61 tumors were detected in 43 or 49 patients. And this I think is the key taker point here is that when you look at the five year overall survival meeting, um what percentage of these patients were alive five years later? Um 88.8% of patients in the surveillance group were still alive versus 59.6% of patients in the non surveillance group. And so this strongly supports the fact that doing surveillance studies in patients known to be at higher risk of developing cancers can actually be beneficial as far as catching these earlier and being more able to treat them effectively. We now are are recommended protocol. Is is in large part based on this Toronto protocol and we actually call it the Toronto surveillance protocol. Um and this is just a summary of what we recommend for surveillance. So from ages birth to 18 years of age, These patients should undergo complete physical examination every 3-4 months, including paying attention to blood pressure, um their height and weight measurements um with particular attention to rapid acceleration and weight or height. Um looking for cushing avoid appearance any signs of civilization including pubic hair Axler moisture, adult body odor. Um hair loss, clutter omega lee or you know, growth and also a full neurological assessment. And we also recommend that these these Children and families seek prompt assessment with the primary care physician for any medical concerns. Um specifically to screen for adrenal cortical carcinoma. We recommend an ultrasound of the Abdomen Pelvis every 3-4 months. Um and sometimes these are done in conjunction with blood tests every 3-4 months, including total testosterone. Um and some other hormone levels that you can see here to survey for a brain tumor development. We recommend an annual brain MRI initially with contrast. Um and then it can be done without contrast if the prayer skins have been normal. Um and then an annual whole body MRI to look for soft tissue and bone sarcomas. Um, and I just wanted to include reference to some of the great support groups out there. So there are there are essentially support groups for every cancer syndrome you can think of. And here this is a big one for lead from any, this is called the lead from any syndrome association. Um, I included their website here and they have really valuable information as far as just what is the syndrome. What resources are available. Patients support links. Um and then uh, news and information. And they also organized a number of events. So it's nice to be able to connect families um, patients to others who have similar syndrome. Next, I wanted to talk about P 10 hammer tumor tumor syndrome or phds. this actually encompasses several different autism, a dominant disorders that have um some overlapping features in some distinctive features. The most common are Cowden syndrome, Annie and Riley Ruvalcaba syndrome. Um and then some people include a syndrome called P-10-related produce like syndromes within this family. Um They share a number of shared clinical features, including microcephaly, probably poses of the gi tract like pumas, vascular malformations and then intellectual disability and autism spectrum disorders. And these syndromes carry significant lifetime risks from malignancy, including breast endometrial colorectal renal cell melanoma, thyroid cancers in Children, thyroid cancer represents the predominant risk. And that's what we tend to focus our screening on the most. The prevalence of these syndromes is not entirely well defined, but the prevalence of cabin syndrome, for example, is estimated to be at least one and 200,000 individuals. So as I mentioned, thyroid cancer is predominant type of cancer we see in the pediatric population. Um It's most often a type of thyroid cancer called epithelial differentiated subtype. And this has been reported up to one third of patients who are diagnosed with this syndrome, the earliest reported case. Um I was seven years of age and and recently there was actually a case for part of it patient of six years of age diagnosed with thyroid cancer. Um And it is estimated that up to 5% of patients with P. 10 hammer Tomatis tumor syndrome under the age of 20 will develop this type of thyroid cancer. So we actually recommend thyroid ultrasound starting at age seven. Um If the initial ultrasound is negative, it can be spaced to every two years and if the initial ultrasound is suspicious um it should be really done annually as well as an annual comprehensive physical exam. It's also important to remember that there is there is also a high rate of benign thyroid nodule seen on thyroid ultrasounds. And so with this frequent screening you increase the risk of finding false positive findings. And so we always um really try carefully to inform families of this risk even before the ultrasound screening begins. Because because there are risks of doing screening and that includes finding things that may not be concerning but can be anxiety provoking. And so we um in the hereditary cancer clinic we work very closely with some of our E. M. T. Colleagues who actually specialize in patients with underlying cancer syndromes and really understand the nuances of of reading these ultrasounds and then deciding when to intervene. So similarly for many, there are some really good support groups out there here is just one P 10 hammer tumor tumor tumor syndrome foundation. Um And I included their length as well. Another syndrome missy is called Dicer one syndrome. This is also autism and dominant. Um And it's due to a mutation of the dicer one gene the most common pediatric uh tumor that we see associate with dicer one is called you're a pulmonary blast oMA or PPB. Um and this is seen in infancy and early childhood. Most often, in fact, 40% of P P. B. S are actually associated with the dice reputation. So even in the absence of a family history, um Germline analysis for dicer one mutations would be indicated in a patient with PPB. There are three types of PPB. Um, types 12 and three um. Type one tends to be primarily cystic in appearance, whereas types two and three have more solid components and types two and three actually can metastasize and can be quite aggressive. This tumor is plural based and so typically seem kind of on the periphery of the lung fields and can actually um lead to pneumothorax. And sometimes these patients can actually present with the pneumothorax is their initial presentation. These patients are also at risk for tumor called Sir totally light XL tumor, which occurs in the ovaries, tends to occur in older patients. So teens and twenties. Um and some of these tumors do release hormones including testosterone and so patients may present with signs including facial hair or deepening of the voice. Another tumor that's seen in this patient population is a kidney tumor called a Wilms tumor and also a benign kidney condition called a cystic from uh These patients can also develop multi modular Reuters, which typically present with thyroid enlargement. These are actually benign lesions intend to very slow growing. So do require just observation and then finally patients with today's from one are increased risk develop pino blast oma. Um when there is involvement of the pituitary gland, they can develop signs of cushing syndrome and also ocular findings. So here are the surveillance recommendations for dicer one as far as the lungs. It's recommended to actually start in the prenatal period with consideration of a third trimester ultrasound to detect large lung cysts that might require urgent information after delivery in the first couple years of life, chest x rays are recommended um every 4 to 6 months. With consideration of a ct scan of the chest as well. And then um as these patients age we recommend annual chest x rays. Um And if patients are diagnosed over the age of eight years, it is recommended to consider a baseline chest X ray or cT scan. Um For patients diagnosed a younger age. If they have not developed PPB by age a um they do not need routine surveillance for that anymore. It's recommended to get a baseline thyroid ultrasound by the age of eight and then to repeat it every three years or with symptoms or with concerning physical exam findings. Um And after for patients who receive chemotherapy and or radiotherapy, it's also recommended to check a thyroid ultrasound uh and then repeat annually. Um gynecologic. Uh The evaluation is indicated including Pelvic and Abdomen ultrasound um to begin at age 8-10 and continue up until age 40. And to look at the kidneys is recommended to an abdominal ultrasound every six months and then once a year from ages 8-12. And these patients that have annual physical exams, a dilated eye exam from ages 3-10, and then also education about some of the symptoms that can be anticipated. And these these tables are actually pulled from an actual patient note of a child that we follow in our cancer clinic. Um and we provide this in written form to the families as well as help set up the screening exams on the scans. Here is a family support group for a day. So when syndrome and then I wanted to talk briefly about another syndrome called hereditary leo mayo mitosis and renal cell cancer syndromes. So this is another autism, a dominant syndrome. The vast majority of these cancer syndromes are autism, a dominant. Um This one is caused by variance in a gene called the commemorate hydro taste Gene, or F. H. These patients typically present with skin lesions called leo melanomas. Um And I included a sort of a classic photo here. They really have a wide variety and how they can look though. So if you look up um this syndrome, you'll see multiple different appearances to these lesions, but in general, their firm, not popular or nah jewels and they can be flesh colored or actually reddish or brown in appearance. Um They tend to tend to be on the extremities and the trunk and less often on the head and neck. Often these lesions are painful. Pain is sometimes you get a history that pain can be elicited by touch cold or heat and these tend to increase in prevalence with age. We also these patients are also at risk for uterine lesions. Um And these actually developed in up to 80% of female carriers and tend to occur at a younger age than uterine lesions in other patients who do not carry this mutation. These can present with symptoms including menorahs, asia abdominal pain or excessive menstrual bleeding. Um And these patients also have an increased risk of developing renal cell carcinoma which unfortunately is often metastatic at the time of diagnosis. Uh Here is a recommended surveillance protocol for this group of patients. And so you can see that um MRI is looking specifically at the kidneys starting at age eight and continuing annually. Good skin checks by the primary care pediatrician and dermatology as needed. Um and then gynecological exams and ultrasounds As uh starting at age 20. And here is a a support group for patients with H. L. R. C. C. So just a little bit about our pediatric hereditary cancer clinic or ph C. C. Um This is a comprehensive clinic that includes genetic counselor Nicola cadenas on the upper right, Jessica Tenny who's a medical geneticist and then there are three of us oncologist dr mignon low on the left and myself there on the bottom and then a room round of swimming. We also have a nurse practitioner Elena without who did not have a photo to provide. And we offer this clinic twice a month. Sometimes more often is needed. Um During the past 1.5 years now with the covid pandemic, we've actually been able to see the majority of patients by video business which has been nice. Many of these patients come from quite far away. Um uh And we're able to as possible coordinate for scans, ultrasounds blood tests locally as much as possible. Um So it's it's been really nice continuity for these families. Um In select cases we have been bringing patients in even during the pandemic. Um and the goal is to get back to more in person visits in the future. So we offer through this clinic really comprehensive genetic counseling services for families. Um And it includes care for the whole family. So you know we'll have the patient who's the pro ban but we also help coordinate um and arrange for testing for siblings and parents. Um as needed. Many of these tests can be done actually by buccal swabs that can be mailed to the family's home which is nice. So they don't even have to get blood drawn or come in to the clinic. And so we're able to really explain to the family how to perform the buccal swab on their Children or on themselves and they get it sent back to the right lab. Um It's important if you do want to make a referral to our hereditary cancer clinic that you don't put in the referral to just pediatric genetics. That actually goes into a different Q. Um And so I did put our clinic phone number and fax number here as well as my email address. You can always feel free to reach out to me. Um For those of you who are using apex, this is how the order looks. It's actually ambulatory referral to cancer risk genetics. This will funnel it into a queue that includes adult and pediatric patients. And then um the person receiving the riff from triage as appropriate. Here is a list of our entire hematology oncology and bone marrow transplant team at Benioff Children's hospitals and how to refer your patient to UCSF mm hmm. And then my references