Expert Care for 22q Deletion Syndrome with Drs. Laura Swibel Rosenthal & Kelly Regan-Fendt

Until recent advances in genetics testing, 22q Deletion Syndrome also known as DiGeorge Syndrome or velocardiofacial syndrome, was often difficult to diagnose. Now, more children are receiving this diagnosis earlier in life and Lurie Children's 22q Deletion Center has assembled a team of experts to care for this special group of children who may face serious symptoms ranging from congenital heart defects to immune system problems and cleft palate. In this episode, Dr. Laura Rosenthal and Dr. Kelly Regan-Fendt explain the strengths of their multidisciplinary team and holistic care plans that can be tailored for each patient’s unique needs. You can help support the clinic here.

“I think the team care is really unique at Lurie Children’s, the core team visit includes genetics, immunology, otolaryngology, speech pathology, audiology, and social work, and we’re adding in  endocrinology. We get together monthly to discuss patients, programming, the future, what could we do better.”

Laura H. Swibel Rosenthal, MD
Attending Physician, Otorhinolaryngology-Head & Neck Surgery; Medical Director, Speech and Language Services; Director, Multidisciplinary 22q Program 
Assistant Professor of Otolaryngology in the Division of Pediatric Otolaryngology, Northwestern University Feinberg School of Medicine 

“We provide resources so patients feel safe and supported. We tell our families there's no small or silly questions when it comes to 22Q and we really want to hear from them.” 
 
Kelly E. Regan-Fendt, MD, PhD
Attending Physician, Genetics, Genomics and Metabolism 
Assistant Professor, Pediatrics in the Division of Genetics, Genomics, and Metabolism, Northwestern University Feinberg School of Medicine 

Show Notes 

• 22q deletion syndrome is the second most common chromosomal disorder, following Down Syndrome, it refers to an area of DNA that is missing on the 22nd chromosome. 
• The phenotype varies widely from one individual to the next, so that one individual can be severely affected and another cannot have any medical problems or any signs of the deletion. 
• Rosenthal leads the multidisciplinary team at Lurie Children’s, dedicated to treating 22q deletion syndrome. 
• Regan-Fendt says genetic testing and early interventions can help families navigate 22q deletion syndrome. Lurie Children’s provides comprehensive genetic counseling to assist families with information and help coordinate next steps after diagnosis. 
• The center includes same-day access to pediatric specialists in genetics, immunology, otolaryngology, speech pathology, audiology, social work,  endocrinology and cardiology.  
•  Treatments for  congenital heart disease,  unique vocal cord pathologies, and cleft palate are among the procedures and surgeries performed by the team in early stages of life.   
• Nearly 60% of individuals with 22q Deletion are at risk for increased infections and immunodeficiency with the time of highest risk generally being in the first year of life.  
• Lurie Children’s participates in education and community support for families with projects like  ”22Q at the Zoo” day to raise awareness of the syndrome. 
• As children age through adolescence, the team helps families identify adult care and resources for a smooth transition into adult healthcare.

Transcript

[00:00:00] Erin Spain, MS: This is Precision Perspectives on Children's Surgery from Ann & Robert H. Lurie Children's Hospital of Chicago. I'm your host, Erin Spain. On this podcast, we introduce you to surgeons at one of the country's most renowned children's hospitals to find out how they are transforming pediatric medicine.Today, we are talking about a genetic disorder called 22q Deletion. After Down syndrome, it is the second most common chromosomal disorder. And prior to modern genetic testing, that is now available it was previously much harder to diagnose. It's known by other names such as DiGeorge Syndrome and refers to an area of the DNA that is missing on the 22nd chromosome. 22Q can present in many different ways with serious symptoms ranging from congenital heart defects to immune system problems and cleft palate. While there is no cure, many therapies and medical and surgical interventions are available to help address symptoms and help children with the disorder get the care they need. Lurie Children's is home to a multidisciplinary care team whose sole focus is 22q Deletion Syndrome. Today, we welcome two members of the 22Q team to give us more insight into this condition and how its multidisciplinary team of providers work together to serve young patients and families. Dr. Laura Rosenthal is a pediatric ENT specialist and surgeon here at Lurie Children's. She leads the 22q Deletion team and Dr. Kelly Regan-Fendt is a clinical geneticist at Lurie Children's who specializes in 22Q. Welcome both of you to the show. 

[00:01:38] Dr. Laura Rosenthal: Thank you for having us. 

[00:01:40] Dr. Kelly Regan-Fendt: Good to be with you. 

[00:01:41] Erin Spain, MS: Well, Dr. Rosenthal, let's start with you. I mentioned that 22q Deletion Syndrome is almost as common as Down syndrome. Explain this condition to me and why so many people have never heard of it. 

[00:01:52] Dr. Laura Rosenthal: Yeah. So it is the second most common genetic syndrome not nearly as common as Trisomy 21 or Down syndrome. It's about one in 2, 000 to 4, 000, Down syndrome is about one in 600 to 700, but it does make it the second most common genetic syndrome. And the phenotype just varies so widely. So one individual can be severely affected and another cannot have any medical problems or any signs of the deletion. Sometimes there may be a few small things that are kind of going on that eventually It is explained by 22q Deletion Syndrome and often patients may go through what we refer to in our literature as sort of a diagnostic odyssey to figure out like, well, why are all these things happening? And eventually we can find 22q Deletion Syndrome. So it can be de novo, which means it's new, or it can be inherited, and it is autosomal dominant, so if a parent has it, they may pass it on to their children. But we do have Kelly here to explain the genetics of it. 

[00:02:55] Erin Spain, MS: That's right, Kelly. You, as I mentioned, are a clinical geneticist here at Lurie Children's and genetic testing , early genetic testing and diagnosing 22q Deletion Syndrome is important. So talk to me about that, kind of take me through this process of how families get a diagnosis if this is suspected. 

[00:03:13] Dr. Kelly Regan-Fendt: Yeah, absolutely. That's a great question. It's actually a really personal one for a lot of our families. So establishing a diagnosis earlier certainly allows us to prepare for, and in some cases, prevent some of the health issues that we can see in 22Q. In terms of making the diagnosis with genetic testing, I will say our genetic testing capabilities have really advanced rapidly over the past several years and decades, and we are able to perform both genetic screening tests and diagnostic tests during a pregnancy. So it's possible to establish a diagnosis during a pregnancy. However, this is a really personal decision and many of our families prefer a genetics evaluation after a baby is born. So there are a few different genetic tests that we can do that can detect this 22q Deletion. The most common one we use today is something called a microarray. And this really can detect, are there pieces of our DNA that we're missing or do we have extra copies of? And it kind of gives us the address or the exact coordinates on chromosome 22 where this piece of DNA is missing. 

[00:04:15] Erin Spain, MS: You mentioned this can be done during a pregnancy. Is this something that's typically screened for during pregnancy or would it be something that a mother would have to request. 

[00:04:23] Dr. Kelly Regan-Fendt: Yeah really depends on what else is going on in their pregnancy. If there is a heart difference, for instance, that's identified during a pregnancy we can offer both screening tests from a blood test or what's called an amniocentesis, kind of sampling the amniotic fluid and doing a diagnostic genetic test to look for 22Q. 

[00:04:42] Erin Spain, MS: I imagine the role of a genetic counselor is very important in this diagnosis. Tell me about the role of the genetic counselor for families affected by the 22q Deletion Syndrome, and what sort of questions they're able to answer. 

[00:04:53] Dr. Kelly Regan-Fendt: Yeah, so we're really fortunate to have a genetic counselor who has expertise in 22Q and is really passionate about this condition. Her name is Valerie Allegretti and she works really closely with our families and the rest of our team. One important role that she plays is counseling a family after they are first, given the diagnosis, and our families may be hearing about their diagnosis for the first time in different ways. Some might be through like a prenatal genetics evaluation. Others may be from a NICU provider or their pediatrician. So actually, before being seen in our multidisciplinary clinic, Valerie will often have a telemedicine appointment ahead of the visit with the family to really take the time that's needed to get a sense of the family's understanding of 22Q kind of review how this happens from a genetic standpoint and really prepare them on what to expect and how we can help them when they come see us in clinic. If a family's interested in learning more about whether this was an inherited. Or learning more about the chance of having another baby with 22Q. She can review that information with them and coordinate any additional genetic testing that's needed or requested. 

[00:05:58] Erin Spain, MS: What are those top questions that parents have after they receive the diagnosis and they're brought into the program, to the clinic? 

[00:06:05] Dr. Kelly Regan-Fendt: So some common themes that we hear from our families include, you know, what will my child's development look like? What other health complications can I expect? And, you know, what can I do to really help their physical, mental, emotional health? And I think really to begin To address these questions, one important aspect of 22Q is that it really is such a spectrum of differences that we can see in terms of health problems, developmental outcomes. And at the same time, we know that we're more than just our genes and that things like developmental therapies play a really big role in helping children reach their developmental potential.  We also emphasize that as we're doing more genetic testing, we are identifying more individuals who appear to be, you know, more mild in terms of their symptoms. And sometimes we even identify a 22q Deletion in a parent of a child who was recently diagnosed who is, you know, previously healthy, otherwise had no idea that they also had this genetic condition. And so when we see families in our clinic, we really take a holistic approach and review their health from head to toe.

[00:07:03] Erin Spain, MS: So Dr. Rosenthal, the Lurie Children's 22q Deletion Program was the first of its kind in Illinois to be set up so that patients and families can see multiple providers from across multiple specialties all in one day. Why is this so important? 

[00:07:18] Dr. Laura Rosenthal: It was one of the first of its kind in Illinois, our first patient was born in 1965, although technically the clinic started in the early 2000s. We've served over 400 patients in the last 10 years and many patients are seen outside of team visits. But there is the opportunity to have team visits for patients and families that would like that kind of multidisciplinary care and convenience of coming just one morning, seeing all the providers in one day, and knowing that we are all communicating with each other that day to kind of come up with the best treatment plan for the individual patient. It can be a little bit of a long morning for some patients, and we do lots of fun things with them to keep the families and the patients engaged. For patients who have local cardiologists or local endocrinologists, we are happy to work with their providers, but we also do provide a multidisciplinary team day and in our clinic, patients may arrive around seven 30 or eight o'clock in the morning and that morning can see audiology, ENT, genetics, immunology, social work, and speech pathology. We also work really closely with cardiology, and they're not in the clinic, but they have a really complementary multidisciplinary clinic that has providers that also include all of those providers that you would want to see that aren't in our clinic, so it's really very nice. And in their clinic, they may have developmental peds or neuropsych or physical therapy or occupational therapy. And so for patients who are seeking multidisciplinary care, there's a lot of opportunity at Lurie Children's for that. But I will say for those that do have providers that are seen outside of the clinic, communication is still really nice and easy and smooth and so we really can tailor the care to the individual patient. They can also have labs drawn or x rays or whatever other supplemental things they need to do that day.One of the, important aspects of participating in that 22Q team care is that we do offer a really proactive health care experience for infants, children, adolescents of any age who are diagnosed with 22q Deletion Syndrome and the overall goal is to achieve the best quality of life for that particular patient and family, and it needs to be in a manner that's consistent with their values and fits into their life. So we really do take that to heart and believe that this comprehensive kind of care requires a multidisciplinary approach. 

[00:09:53] Dr. Kelly Regan-Fendt: We're also excited that endocrinology is going to be joining our team . So that's another group that we're excited to have see our patients as part of the multidisciplinary group. 

[00:10:02] Erin Spain, MS: How does being here in Chicago allow you to support such a large team of experts ? 

[00:10:08] Dr. Laura Rosenthal: We are in the great city of Chicago. It's the third largest city in the country. And because of that, we do see a lot of patients. I think it is harder to have a multidisciplinary team with all these different specialists and all these sub specialists in pediatric care in areas that are less densely populated. By nature of where we are and being in the middle of the country, it's great for patients who live here locally, but there are patients who travel from all over the state, as well as neighboring states, and even from other areas of the country and from around the world to be able to get the care that we can provide here. 

[00:10:46] Erin Spain, MS: Dr. Rosenthal, for the patients who are born with a more serious condition, maybe a cleft palate or have a heart condition, surgery may be recommended, sometimes even early in life. Tell me about some of these procedures and how the team works together with the family to decide when to do these surgeries. 

[00:11:02] Dr. Laura Rosenthal: So for many patients who know there's a diagnosis at birth, It's often because of congenital heart disease that may have been picked up in utero or early in life, and often some of those cardiac procedures happen at a really early stage, but it depends on the condition of the patient. Otolaryngology is often involved in this stage, and we can coordinate care and perform a laryngoscopy or bronchoscopy at the same time as any kind of cardiac. There are some really unique vocal cord pathologies that are sometimes found in 22q Deletion Syndrome patients. So often we're involved from an early age. Sometimes for things that are very common, like a patient didn't pass a newborn hearing screen because there was fluid in the middle ear and they may need ear tubes. For patients who do have a cleft palate. Sometimes it can be repaired at around 12 months old. If there's a true cleft palate, but for many patients with 22q Deletion, a cleft palate is not always obvious at first. Not all patients have a cleft palate. Some patients have what's called a submucous cleft palate where the muscle is not intact, but the lining is. And so it's not always picked up right away or it may not cause any problems if it's really mild. Sometimes the palate's completely intact and there is still a problem. And the problem that we sometimes pick up is called velopharyngeal insufficiency, which means that the palate isn't hitting the back wall of the throat completely when you speak and there can be nasal escape of air or too much air can come through the nose with speech. And so sometimes we have to perform a surgery to improve the speech. And so the timing of that surgery varies per patient, but in our clinic, speech pathology and otolaryngology are present together and we perform the evaluation together to determine if someone needs surgery or what the optimal timing of that surgery would be. And sometimes that's closer to four to seven years old, or it could be even later if the patient wasn't diagnosed with a problem until later. 

[00:13:06] Erin Spain, MS: Dr. Regan-Fendt, could you explain how 22q Deletion Syndrome may affect the immune system.What treatments are available to manage immune deficiencies in affected children? 

[00:13:16] Dr. Kelly Regan-Fendt: Yeah. So we know that about 60 percent of individuals with 22q Deletion are at risk for increased infections and immunodeficiency and the time of highest risk is generally in the first year of life. And that's because children with 22q Deletion have very small or sometimes absent thymus glands, which help produce one of our main infection fighting cells called the T cells. So T cells help us fight against viral infections so sometimes if a child with 22Q gets a virus, it can just take longer for them to recover from that infection. T cells also help tell the rest of our immune system what to do and help us remember what infections we had in the past. So again, children can have multiple back to back infections where the body can't remember what infections they had in the past. So our immunologist Dr. Elizabeth Lipner does really careful evaluations of our patients to understand their infection history, their risks for infections, and monitors these specialized immune system labs and makes plans with our families to recommend certain vaccines at certain times. One kind of important consideration is live vaccines. So these are recommended at certain ages in the general population that we might actually delay some children with 22Q if they have evidence of immunodeficiency. But overall for most individuals, we do see improvement in their T cells over time and some individuals do need more interventions with different treatments like IVIG and in some rare cases actually getting a thymus transplant. But I think this is actually just another great example of that multidisciplinary approach to care and how that can be really helpful, caring for a child with medical complexity. You know, there could be many reasons for a child with 22Q to be at risk for infections, whether that's a low number of T cells or poor nutrition or some other anatomical risk factor like a palate issue or reflux that puts them at risk for aspiration and lung infections. So, I really feel very fortunate to be part of a team that's putting our heads together to try to address all these different aspects of health to keep our patients as healthy as possible. 

[00:15:16] Erin Spain, MS: So you mentioned as children grow, they may have a better outcome. Maybe able to produce more T cells, but are there other challenges that may present as a child grows with this syndrome? 

[00:15:27] Dr. Kelly Regan-Fendt: So one of the most common challenges in the early years is feeding and difficulty gaining weight. So we track weight really closely on specific 22q growth charts. And we set families up with any other evaluations or interventions that are needed to help support a child's nutrition. We work really closely with a speech pathologist in the 22q clinic to evaluate for other signs of feeding issues and, help coordinate appropriate follow ups and evaluations like swallow studies. And as patients grow older and sometimes grow out of these initial feeding issues, they might actually be at increased risk for things like obesity and obesity related health issues. So kind of regardless of what end of the spectrum a patient might be on, we really work with them and the families to support healthy weight over their lifetime. Another common question we do hear from families, in terms of what things to look out for, is their child's mental health. And we know that individuals with 22Q are at increased risk for some neuropsychiatric conditions. So we really emphasize early screening, awareness, and detection of these conditions, as we can treat many mental health conditions with therapy and medications. And for most families, we recommend an evaluation by a developmental pediatrician at some point. And part of that evaluation is actually to identify areas of strength, you know, whether that be areas of strength in learning or coping mechanisms, and really trying to find strategies to use those areas of strength to really support the areas where they might need more help.

[00:16:51] Erin Spain, MS: So families often express how comforting it is to know that the 22Q team understands these challenges they're facing. How does the program ensure that families feel supported and heard throughout the child's care journey? 

[00:17:04] Dr. Kelly Regan-Fendt: Yeah, so we always want to support our families and hear their unique stories and perspectives. So even before they come to a visit with us, we have a child life specialist named Jessica who will contact the families ahead of the visit to really prepare them for what to expect for this kind of long day, discuss any really child specific concerns the family might have and come up with ways to make the child feel more comfortable when they come and see us. And we're also really fortunate to have a social worker who's devoted to our 22Q families, Jalen Clemens. He really has expertise in navigating different aspects of living with 22Q, you know, whether that be at school, work, family dynamics. He also helps us to assess for mental health concerns and connects patients to resources so they feel safe and supported and, you know, in between appointments we're always available to talk over the phone or send messages through the MyChart portal and, you know, we tell our families there's no small or silly questions when it comes to 22Q and we really want to hear from them. 

[00:18:00] Erin Spain, MS: Just describe some of these incredible families to me. The progress that you see through your program that maybe wouldn't have been possible if these families wouldn't have found you all. 

[00:18:10] Dr. Kelly Regan-Fendt: I love hearing stories about, you know, what kids were doing on summer vacation or what plans they have for different sports or activities. I remember I had one teenage patient who was really excited about trying out for their school musical and just having a lot of fun with that. We love to ask about their interests again to see, you know, are there areas that they're passionate about, areas of strength that they have that we can help promote with their families and at school. 

[00:18:36] Dr. Laura Rosenthal: Yeah. I think one of the interesting things about the otolaryngology perspective is that when patients come to me, they don't always have a diagnosis of 22Q. It's something that an astute ENT might be able to pick up that possibly someone hasn't picked up before. So there are a lot of patients who may have had a little trouble swallowing or a little reflux over the years or a little trouble sleeping. Occasional ear infections, some speech delay, when they come to see me I'm able to kind of put this all together and think there is something that probably can explain all of this. It doesn't matter what the genetics are, we're going to treat the patient, how we're going to treat the patient. But sometimes having an explanation is super helpful for families and really helpful for moving forward and for knowing what to expect in the future. Sometimes if there is an anomaly, a family might wonder, well, is this a sign of something else and rarely, but like sometimes it is and so for me, some of the like most unique patients are the ones who had these subtle problems that I've seen every day in my normal ENT clinic, but for this unique population, if their speech was maybe even just mildly hypernasal. Maybe they had a little escape of air through their nose, but they're really hesitant in school to speak up because they know that they don't sound quite how they're supposed to. And it's not because their articulation is off. It's not because they're doing something wrong. It's physically, they can't make the sound that they need to be able to make. And sometimes we can operate on that and just make that space at the back of the palate a little bit narrower. And then to see these patients come back with confidence in speaking really can change their quality of life. And we do measure quality of life. We have very specific quality of life scores that we give to these patients that are just related to their speech. It's really nice to see these patients really thrive after coming into the clinic and participating and we put them through a lot and sometimes, you know, between lots of clinic visits and surgery. The surgery can be a little bit hard. It's inpatient surgery, it's a couple hours, there is a week or two of recovery afterwards, but it's worth it. It's worth it to see that improvement in the quality of life for those patients and the joy that can bring to them and their families.

[00:21:05] Erin Spain, MS: Your role with these families doesn't end inside the hospital walls. You're also participating in some community involvement and making these families feel connected and supported. Can you tell me more about that? 

[00:21:16] Dr. Laura Rosenthal: Yeah. So one of the things that we are really excited to bring back this year is the 22Q at the Zoo Day. It's actually a worldwide event. This will be our second annual event, but we are dedicated and committed to making sure that Illinois is always on the map for where in the world can you go to participate in this 22Q at the Zoo day. Providers, families from around the world are doing this. But we work with patients and families in the community to bring everyone together and have an educational and social and fun event to really raise awareness for 22Q. And then we've done a lot of things to try to improve the experience of the clinic day and a lot of these things are really fun for the patient. So Kelly mentioned our child life specialist, Jessica, who prepares families in advance and is also present during that day to help them through the clinic. We've also provided patients with a 22Q passport where they have a little picture of themselves on the front and it has a care plan and areas for notes and how to contact their providers, but has lots of pages where they get stamps and stickers and everything's dated when they go by to see each provider that day to really keep them engaged and make it fun, but it also actually becomes like a really nice clinical document of their labs and when they were seen, what their plan was, and what the plans are moving forward. 

[00:22:48] Erin Spain, MS: So this transition from pediatric care, this incredible program you all have built, into adult care isn't always easy. How do you help patients graduate from the program and find high quality care as adults? 

[00:23:01] Dr. Kelly Regan-Fendt: Yeah. So this is a really important topic and something we're still continuing to work on. And we collaborate with our social worker, Jalen as well, and other folks in genetics who have experienced doing this for other rare diseases. So, you know, one key to success is starting to have this conversation earlier. So kind of in the late teen years, we'll start to ask about, you know, what care providers our patients are regularly following with and to help identify those adult specialists and provide those referrals. Fortunately there are, you know, published healthcare guidelines for adults with 22Q. So we review those with our families and help go over them with the other adult care providers as we transition them. 

[00:23:40] Erin Spain, MS: What message would you like to give to families? Maybe one who just had a diagnosis in their family and they're just getting started on this journey. Why should they consider coming to Lurie Children's and the multidisciplinary 22q Deletion Syndrome program here? 

[00:23:54] Dr. Kelly Regan-Fendt: Coming to Lurie Children's and being seen as part of our multidisciplinary clinic, we really want families to feel like we're a part of their family and we're part of their extended support network. And we're with them through every step of their diagnosis and as their child grows. And we're here to help support their medical needs, but we're here to also help celebrate all of the joys in their life. And, you know, to remind them that this is, again, just one piece of who they are. 22Q doesn't define anyone but just kind of extends into this larger family where we can all help and support one another.and we do certainly see individuals growing up, going to college, you know, living independent lives, semi independent lives, with support of their families. We see them have different talents, different areas of strength, different interests that they pursue and, you know, we help them in those pursuits. 

[00:24:47] Dr. Laura Rosenthal: I think the team care is really unique at Lurie Children's. Again, the core team visit includes genetics, immunology, otolaryngology, speech pathology, audiology, and social work. And we monthly get together to discuss patients, programming, the future, what could we do better? We have added endocrinology, as Kelly said, we have active participation in cardiology in our team meetings and in our programming outside of the clinic day, we have experts in cardiothoracic surgery and radiology, general surgery, urology, plastic surgery, developmental peds, neuropsych, and anesthesiology, and other therapists and they're all dedicated to the care of children. I do think we have amazing providers and all of these areas of expertise. Not every single patient with 22q Deletion Syndrome is going to need to see all of those providers, but all of those providers see patients with 22q Deletion Syndrome. And they're all specialized in pediatrics. It is an academic institution, and while we all are really on top of the latest care and participate in research, we are also educating the next generation. All of the medical students and residents that rotate with us are also learning from these patients and are going to take what they learn to provide the best care for patients when they leave Lurie Children's. 

[00:26:17] Erin Spain, MS: So any parting thoughts today for listeners, parents, families who come upon this podcast, anything that you would like to leave us with today? 

[00:26:25] Dr. Laura Rosenthal: Lurie Children's is a great place to be. It's why I'm there. I think it's really welcoming for both providers and families. And we are so honored to be able to care for your child. 

[00:26:35] Dr. Kelly Regan-Fendt: I feel really fortunate again to be part of this team where we all work together in caring for our patients and we all collaborate so closely. So, you know, when your child's being seen as part of our team, you really are getting that thoughtful team approach. 

[00:26:49] Erin Spain, MS: Thank you so much for being on the show and talking about the program. We really appreciate all of your insight today. 

[00:26:55] Dr. Laura Rosenthal: Thank you. It was a pleasure. 

[00:26:57] Dr. Kelly Regan-Fendt: Thank you so much.

[00:26:58] Erin Spain, MS: For more information, including how to make a referral or an appointment, visit luriechildrens.org.