How Do I Create A Family When I Have An RB1 Mutation?
Monday September 16, 2019
Individuals who carry an RB1 mutation have a 50% chance of passing the retinoblastoma cancer syndrome on to each child. Melissa Mills, bilateral retinoblastoma survivor and genetic counsellor, explores the psychological and physical impacts of this experience, and the different routes to creating a family when a prospective parent has an RB1 mutation..
Contributors: Melissa Mills, Jessica Givens, Leanne Merren and Angie Campbell.
How do I create a family when I have an RB1 mutation? That is a very common question, and difficult to answer, because there is no one right way. In fact, there are many ways to have a family. Although many cultures have serious pressure regarding “having a family”, families are defined by the people in them, and what is best for them.
In this article, I will share stories from different survivors who found their own way to having a family. I will also do my best to review the prenatal testing options. Please keep in mind that everyone is different, everyone has different lived experiences, and what’s right for one family could be completely wrong for another. We hope all the information and experiences below will help you on your own journey.
Deciding How To Make Your Family
Several different survivors share their stories.
I was an only child. My parents made this decision after I had retinoblastoma, for a couple of reasons. First, there was a lot of pressure for them not to burden themselves, or others, or their child with this disease. Also, my mother took me to treatments alone, while my father stayed home to work. It was a lot of stress on a young couple.
As I grew, my mother mentioned it to me. She had a passion for children and was saddened by her choice. I learned from her not to let others tell me that my children, or myself, were not valuable because of this disease. I knew early that I hated being an only child, and that I wanted multiple children.
When I was 19, I met Patrick. I had dated before and I think my poor vision didn’t let me see my imperfections from the cancer. Or maybe I’d been told enough that I was cute or smart or skinny. I didn’t have any sort of poor self-confidence. I was very comfortable talking about my eye and my disease, although I wasn’t (am still not) comfortable taking my eye out. After Patrick and I had dated for several months, we talked about our goals; educationally, professionally and relationally. It was easy for me to share that I wanted children – more than one, and probably more than two. He knew the risks just as I did.
Once we were married, we had children. The first didn’t have rb. Some made comments that we had gotten lucky and should stop. We had a second child, and although we knew the risks, it was sort of painful to hear that he had retinoblastoma. It meant a lot of reading and a lot of learning about current treatments and others with this disease. It was almost like it was new to us. Well, it was a new perspective for us. Parker lost an eye. I only have one eye. I was so conflicted. I knew that he would be fine. But I also knew that some would ask questions, so I knew he would have to be prepared to answer.
During the stress of enucleation, our third child was conceived. When he was diagnosed, there were a lot of comments about “I thought you were done with two”, and “did you intend to get pregnant?”. Patrick and I decided not to get angry, but to either ignore the comments or also to quip back with comments like “well I don’t have a girl still”.
The hardest questions were from those who knew the disease and knew there was a way to genetically implant only embryos who did not have the disease. To an outsider, this seemed perfect! Avoid the disease all together. To us, it seemed to be throwing away children who had value.
My father, myself, my second born, and now my third born – we are all valuable people who bring worth to this world. We could never imagine throwing away these “unhealthy” embryos. It just wasn’t something we could have made the choice to do. In my mind specifically, it would have meant that my family is less because our genetics cause disease. And to me that was ridiculous, so many people have genetic predispositions to cancer or heart disease or diabetes, and if we begin throwing away all of these people, what exactly are we doing?
Today, all three of my children (ages 17, 11 and 9) are in gifted programs at school and are hard workers. The two with retinoblastoma don’t let their vision or late effects from chemotherapy define them. We have given them the words to describe their disease and how it has affected their bodies.
I would not want for anyone to be sick or hurting. But for retinoblastoma in my life; I am grateful for this story to tell.
As I grew up, all I wanted to do was be a mum. I had no idea that the cancer I had as a baby would mean this simple life plan would turn into an 18-year-long traumatic and emotional journey.
My firstborn boy, Kieran, inherited my mutated gene and had to endure 20 months of active treatment to save his eyes. This had a devastating impact on both Kieran and myself. I knew I didn’t want him to be an only child, but I also knew I was strong enough to go through that again.
When Kieran was two years old, a conversation with Dr. Elisabeth Rosser, retinoblastoma genetic counsellor, gave me hope that I could have another child, and not pass on my mutated gene. She referred us to University College London Hospital (UCLH) and we began the process of Pre-implantation Genetic Diagnosis (PGD). It sounded so easy and an answer to my prayers. I had no idea it would take four years of trauma before I would meet my second son.
We were the first people in the UK to go through the PGD process for cancer, and therefore had to go through the battles for funding, the Human Fertilisation and Embryology Authority (HFEA) approval process, the huge media exposure, and the wait for the UCLH team to develop the techniques needed to carry out the treatment. It was excruciatingly difficult, but we were very lucky the treatment worked first time. I had a healthy baby boy, Cameron, who did not inherit my faulty gene.
My path to motherhood had been so challenging and heartbreaking, in so many ways and over so many years. I felt extremely blessed to have my two boys who were both healthy and happy. But also sad that I would not have the large family I desperately wanted. I decided to become a foster carer – I may not be able to have any more children of my own, but I could be mum to many vulnerable little ones who needed my love.
Little did I know this decision would lead to me meet my youngest two sons. Dane came to me at two days old and was loved unconditionally from that moment on. He officially became my son at the age of two when we were unable to find adoptive parents for him, but I believe he was always destined to be my boy. We have since also welcomed Dane’s younger brother, Finlay, into our family.
So I was a mum to four beautiful boys, and time was healing a lot of the old wounds. My eldest was 17 and I was a very different person to the 23-year-old who nursed her son through cancer. My husband and I decided to try for one last child.
We did this with the full understanding that the baby may inherit my gene, but I had reached a place in life where I was OK with that. We had an amniocentesis test when I was 16 weeks
Pregnant, and only a few days later we received the most amazing call. Our baby did not inherit my gene mutation, and we were having a little girl. The relief and joy were truly overwhelming. Millie arrived and completed our family in March 2018.
Looking back, it feels as though my whole adult life has been spent trying to achieve this family, but I cannot think of a better use of my time or energy. I may not have taken the conventional route to get here, but I have the children I dreamed of and I love every second of the chaos and noise.
Retinoblastoma wasn’t something I ever thought I could pass on to my children. My left eye was enucleated at 11 months old, and cryotherapy saved the vision in my right eye after several small tumors were found in that eye as well. My parents and my doctors had the mindset that cancer was not something to take lightly, and I took that to heart. I also knew and felt the devastation my diagnosis and treatment was for my parents. I struggled for many years with anxiety and depression.
Adding a child who needed to be shepherded through the process of surviving retinoblastoma was not something I felt I wanted, or had the emotional bandwidth to handle. I married someone who also didn’t want to have a child with cancer. So I spent a lot of time researching my options, and we chose what was best for our family.
Ultimately, I chose to do IVF and PGD. It wasn’t an easy process. In truth, it was so difficult that I sometimes second guessed myself, which was very unexpected. But I was resolute, and in my mind, I would have stuck myself with thousands of needles to protect my child from cancer.
My father always said that he wished with all his heart that he could have traded places with me as I went through all the medical procedures associated with retinoblastoma. I feel like that’s what I did, I traded places with my children. I went through too many procedures and injected too many needles into my own body to count, so they would never have to. This was a gift to my children, and ultimately to myself, because I know I did everything I possibly could to beat retinoblastoma.
Navigating the Medical Side of Having a Child With or Without Retinoblastoma
We covered some of the psychosocial aspects of having a family as a retinoblastoma survivor. Now we’ll cover the more technical/medical aspects of these decisions.
Below, we will look at:
- Prenatal Diagnosis
- Pre-implantation Genetic Diagnosis
Option 1: Prenatal Diagnosis
There are several ways to find out before birth if a fetus or baby is affected with retinoblastoma.
- Prenatal ultrasound or MRI
- Prenatal Genetic Diagnosis for the fetus
Prenatal Ultrasound or MRI
If the mutation status of the pregnancy is unknown, or if prenatal genetic testing (see below) has confirmed the baby carries an RB1 mutation, prenatal ultrasound and/or MRI may be used in the third trimester to identify tumors early. The pregnancy may be induced (the use of medicine to cause early labor) to allow for early treatment of tumors. Even if no tumors are visible on ultrasound, delivery of the fetus at 36 weeks of pregnancy may be recommended, as 30% of babies with an inherited RB1 mutation will still have a tiny vision-threatening tumor [Soliman et al 2018].
Leanne Merren describes how this option worked for her family
“I had genetic testing when I was 18, so I knew I might pass it on, and I knew to have babies checked immediately after birth to start treatment as soon as possible if tumors were found. During my first pregnancy, I met with the doctor who had treated me, and he told me to contact him as soon as the baby was born. My son was diagnosed in the Neonatal nursery when he was 24 hours old. He started treatment a few days later. My second and third children also had rb, and they were diagnosed very early as well.
All three children kept both eyes. They all have some decreased vision in one eye, but they all play soccer and 2 of them are driving so far. I have been able to help them through their own experiences because I can empathize so well, and I teach them how to watch for any concerning symptoms since I do the same for myself. So far we have all been healthy and have had no other cancer.”
Prenatal Genetic Diagnosis for the Fetus
A study by Soliman et al. in 2016 found that “When a parent had retinoblastoma, prenatal molecular diagnosis with early-term delivery increased the likelihood of infants born with no detectable tumors, better vision outcomes, and less invasive therapy. Prenatal molecular diagnosis facilitates anticipatory planning for both the child and family.”
Before prenatal diagnosis can be performed the parent(s) with retinoblastoma must have already undergone genetic testing to find their RB1 mutation. It takes time to get an appointment, to do the testing, and to get the test results, so ideally this testing should be done before becoming pregnant.
Prenatal diagnosis at this point in time includes a test of the placenta called chorionic villus sampling (CVS ) or testing of cells in the amniotic fluid called amniocentesis. CVS is typically done from 11-13 weeks, and amniocentesis is typically done from 16-20 weeks of pregnancy. The results can take from 2-5 weeks, depending on the type of sample, sample growth, and laboratory used to test for the RB1 mutation.
Prenatal testing requires access to a major medical center. In the United States, you may or may not also need a special insurance authorization, especially if you are under age 35 (these two tests usually are used to look at the chromosomes of the fetus, and are covered once a mother will be age 35 at delivery). You must let your medical team/Obstetrics doctor (OB) know about your wish to test a pregnancy as early as possible, so you can have genetic counseling and have your team coordinate procedures and testing with an appropriate laboratory. Additionally, you must provide your healthcare team with a copy of a lab report with the known RB1 mutation listed on it.
Once you receive the results, either the pregnancy will be affected with retinoblastoma or not. If one parent is a carrier, there is a 50/50 chance in any pregnancy of passing on the mutated (non-working) RB1 gene. (⅔ chance if both parents carry an RB1 mutation).
It’s important to meet with health professionals after receiving a diagnosis. Make a plan ahead of time for receiving this information. Even if you know there is a 50/50 chance – a flip of a coin, it can feel like a crushing blow to hear your fetus inherited an RB1 mutation. I recommend having a therapist that you trust lined up ahead of time, because these are complex emotional issues that may cause surprising emotional trauma for a retinoblastoma survivor. Not all therapists are created equal; if you don’t find a good one on the first try, keep looking.
Feelings can change or be different than you expected during this process. This is not uncommon, and can be especially hard if one partner feels one way about a pregnancy affected with RB1 mutation, and the other partner feels differently. It is extremely important to communicate a lot with each other on how you’re feeling, and what the decisions will mean for you and your family. These conversations are best started before a pregnancy, to avoid conflicting feelings if at all possible.
If the pregnancy inherited the RB1 mutation, coordination is needed with a team of specialists to plan prenatal ultrasound and/or MRI screening, and postnatal eye exams. Expert screening is vital to guide care for the baby, and ensure the best possible outcomes.
Even if no tumors are visible on ultrasound/MRI, or prenatal screening is not done, delivery of the baby at 36 weeks gestation may be recommended to detect and treat tiny vision-threatening tumors as early as possible. The U.S. has developed guidelines for screening of babies at risk of developing retinoblastoma due to known family history.
Termination After Prenatal Genetic Diagnosis
Pregnancy termination is an option for any reason in many countries and states in the U.S. up to the age of viability, although access to these procedures is an ever changing landscape. In general, termination before 13 weeks can sometimes be an outpatient procedure. Termination between 14-20 weeks is available in an OR. Termination after 20 weeks can be more complicated with fewer providers opting to perform the procedure as you approach the age of viability (~20-24 weeks) where a fetus could survive outside the womb, albeit with major medical intervention.
Termination after 24 weeks is available in cases of medical problems at a few select locations. These late terminations are not considered lightly, are not covered by U.S. insurance, and can be very expensive. Keep in mind that with the CVS and amnio procedures, it can take weeks to find out if a pregnancy is affected.
In general, the later the termination, the more difficult it is both physically and emotionally for the patient/couple. This is a personal decision for the retinoblastoma survivor and their partner as they consider what is best for their particular family. This can be even more difficult when the survivor and their partner do not agree on the best course of action. Again, therapy can be a useful tool to help couples navigate these difficult decisions.
Option 2: Preimplantation Genetic Diagnosis
Preimplantation Genetic Diagnosis (PGD) is now also called Preimplantation Genetic Testing for a Mendelian condition (PGT-M). I will use PGD. Whatever name your provider uses, PGD is a way of testing embryos for RB1 mutation before they are transferred to the mom to make a pregnancy.
This option can be very helpful for those who do not want to have a child with retinoblastoma, and do not want to do prenatal genetic diagnosis and termination. But it does require In Vitro Fertilization (IVF) procedures, explained below. A unique test must be developed for each prospective family, from a laboratory that specializes in PGD. It can take up to several months to have the PGD test ready to use for an IVF cycle.
IVF stands for In Vitro Fertilization, basically fertilizing the egg with sperm outside of the body. IVF requires the mom to have eggs harvested, and this is a tough process, especially if she is afraid of needles.
Egg retrieval requires months of pre-planning, cycle tracking, and injections of costly medications. In the U.S. certain larger companies are now offering fertility coverage with their health insurance benefits, but many are not. Sometimes, insurance companies will just cover the medications and PGD testing, but not the IVF costs. The costs and coverage vary widely, ranging from $10,000 to over $30,000 per cycle. Some people travel to other countries where the procedures and testing are cheaper.
Medications used for IVF vary by protocol. The fertility doctor will do lots of tests to decide what they recommend to stimulate the ovaries and grow lots of eggs to retrieve (i.e., remove via a small surgery). Each month, typically one out of 100 eggs is fully matured and ovulates, but with IVF, the ovary stimulation medications helps multiple eggs (anywhere from a few to over 20) to mature for retrieval.
Ultrasounds and Scheduling the core IVF process. Treatment requires many ultrasounds (transvaginal ultrasounds that can be uncomfortable and even painful for some women) and other appointments at very specific times. It can be hard to maintain privacy when asking for so much random, but specific, time off work. Timing of the medications, and especially the final “trigger shot” is extremely important. The trigger shot primes the eggs to be ready for retrieval at the exact time of your surgery.
Men must provide sperm, and this is typically a much less involved process, albeit stressful to provide a sample in a very tight time frame.
Fertilization: After the eggs and sperm are ready, the lab with create embryos in one of two ways:
- Intracytoplasmic sperm injection ( ICSI) involves injecting a single live sperm directly into the center of a human egg. In the past, this procedure was required to do PGD, but this may have changed. Please check with your healthcare providers to see what your center requires.
- If ICSI is not used, the eggs retrieved from the ovaries are placed in the same container as the sperm, and fertilization occurs in the laboratory container.
Embryos are then carefully incubated in the embryology laboratory. If a fertilized egg is developing properly, it will consist of 6-8 cells by 3 days after the egg retrieval. If an embryo continues to develop appropriately, it will form a ball of cells called a blastocyst by 5-6 days after egg retrieval.
Blastocyst testing: At present, the embryo is usually grown to a blastocyst (approximately 5-6 days old) for biopsy. Typically, a laser is used to create a hole in the outer shell of the embryo, and a few cells are removed for use in the PGD test. The embryo is not damaged. However, studies have shown that making a hole in the outer shell of the embryo, and transferring an embryo at day 5-6 after testing, can lead to monozygotic (identical) twinning (Kanter, et al. 2015).
PGD technology: testing to determine if the embryo inherited an RB1 mutation is done by PCR and/or linkage analysis. Please ask your provider what they recommend, and for the latest updates in this field of analysis.
- Polymerase chain reaction (PCR): There is only a small amount of DNA to test from the embryo biopsy, so multiple copies of the gene of interest are made by a process called amplification. This amplification process allows the identification of very small amounts of DNA to make the diagnosis.
- Linkage analysis identifies other genes near the RB1 gene that would likely be inherited together. Blood samples from affected and unaffected family members are required for this testing. Linked genes are determined for each person in the family, and it is determined which linked markers are inherited along with the healthy gene copy, and which linked markers are inherited along with the mutated (non-working) copy. This can be really helpful when there is such a small amount of DNA to work with for PGD testing. When you copy DNA over and over (PCR), some genes don’t get copied as they should; this is called allele dropout. Testing for lots of linked genes, rather than just the RB1 gene, helps ensure accurate diagnosis of the embryo.
Embryo selection: After the PGD is completed, embryos found to be unaffected can be transferred back to the woman’s uterus. Embryo transfer will always be by way of Frozen Embryo Transfer. Fresh transfer is not possible with PGD due to the timescale of genetic testing. Additional embryos can be kept in a cryopreservation freezer for later use.
Drawbacks and Issues to Consider
IVF-PGD is a long and drawn out process that can involve a lot of heartbreak. A person may be otherwise normally fertile and have a difficult time producing enough eggs for the IVF process. Everything needs to go right at all steps in the process.
One needs a lot of healthy eggs retrieved, then one needs as many eggs as possible to fertilize, then the embryos must be chromosomally normal (not all are, especially for women in their 40s). Then it’s a 50/50 chance of getting the RB1 mutation or not.
If you have ever flipped a coin multiple times, you’ll know the RB1 mutation can be passed to the embryos over and over again sadly. This happened to me many, many times.
One time I started with 20 embryos, only 10 fertilized, 6 kept growing, 3 had abnormal chromosomes, and the 3 left all inherited my RB1 mutation. It was devastating. In all, I had to do 6 IVF cycles before I had success. Now I have healthy identical twins.
Some people have the opposite problem and IVF works too well. Some get over-stimulated by the medications, which can lead to other painful health issues. When one has too many embryos, other issues can arise. What does one do with 10 extra embryos? Use them, donate them to others, or pay to keep them in the freezer?
Option 3: Donation
One additional option is to use donated eggs or sperm to have a child. This is much more commonly used than most people think.
Donated sperm is typically carefully screened for genetic conditions and shouldn’t carry an RB1 mutation. This is a fairly inexpensive option when compared to IVF-PGD.
Donated eggs are much more expensive but are also an option if IVF isn’t working out for a person.
Donated embryos are also available. Please visit the U.S. National Embryo Donation Center, or contact your local fertility clinics for more information.
The UK Donor Conception Network provides information and support to individuals, couples and their families before, during and after fertility treatment.
Frequently Asked Questions
1. Can you have children if you are blind?
YES! Leanne Merren has kindly shared the following:
“I have been totally blind due to bilateral retinoblastoma, both eyes enucleated, since I was 2 1/2 years old. I always dreamed of being a mom since I was very young, so I was overjoyed to have all four of my children. I had a lot of support from my mom in the beginning, but I still did everything that needed to be done for my baby, from changing diapers, to feeding, to bathing… The biggest help to me was transportation to doctor’s appointments, and help with filling out paperwork.
I think having a good support system is very helpful, as becoming a parent is a learning experience for anyone, and being blind comes with a few extra challenges. But nothing that can’t be conquered. There are so many systems in place to help, such as medical transportation, and even live agents who can help with paperwork through Aira now.
There will undoubtedly be challenges when dealing with medical professionals and their assumptions that blind parents cannot manage to properly care for their children. But I always approached all of them with confidence, and gave them no room for real doubt. Those who really challenged me were informed that I have a support system, and we would be just fine. This can be a major concern though, as there are many situations where Child Protective Services has been called simply because parents were blind. Many states in the U.S. have been passing legislation against such practices.”
2. How do I know if I have an RB1 mutation or not?
See a genetic counsellor – they can do a risk assessment for you. WE C Hope has a good summary of Retinoblastoma genetics, and a more detailed explanation, including an introduction to genetic counselling, and what genetic testing results mean for the individual and family.
WE C Hope’s co-founder and Medical Director, Prof. Brenda Gallie, co-authored this Gene Reviews article on Retinoblastoma.
If you think you’d like to test a pregnancy or do PGD/PGT-M, see a genetic counselor before you even start trying to get pregnant.
3. How do I find a genetic counselor?
A major cancer center will likely have a cancer genetic counselor on staff, as will large prenatal, maternal and fetal medicine groups. Feel free to call and ask to speak with a genetic counselor.
Not all front desk staff will know what you are asking about, but a genetic counselor will. In the U.S., the National Society of Genetic Counselors provides a search engine to find a genetic counsellor. In the UK, both retinoblastoma treatment teams (London and Birmingham) include genetic counselling, and we recommend contacting the Childhood Eye Cancer Trust for current advice to make contact with the service, if needed.
Support and Hope
Creating and building a family with an RB1 mutation in the mix can be a long, complex, difficult and painful process over many years. Support, understanding and community is vital along the way. Information and support organizations now exist in many countries – find out what exists in your locale, and make the most of the resources and services.
You can often benefit from information and online communities created by organizations in other countries. But bear in mind that the information they provide will usually be specific to laws and care available in that country. Always ask your own doctors for clarification about what is available to you locally, and your personal experience.
Here are a couple resources you may find valuable
About the Author / Editor
Melissa B. Mills is a part-time prenatal genetic counselor at Stanford Children’s – Lucile Packard Children’s Hospital. She has three degrees from Stanford University (a B.S. and an M.S. from the Earth Systems Department, and one from the Medical School in Genetic Counseling). She lives nearby with her husband, 5 year old identical twins, and rescue dog, Derby.
Melissa is passionate about helping people understand genetic information, and about helping protect the Earth. In her free time, she is President of the Mid-Peninsula Parents of Multiples, and Board Secretary for the environmental non-profit Oil Change International. She is also a bilateral retinoblastoma survivor and was treated in the 1970’s at Massachusetts Eye and Ear Institute in Boston, MA.