JOSH FEDER: Welcome to The Carlat Psychiatry Podcast. This is another special episode from The Child Psychiatry Team. I'm Dr. Josh Feder, MD, the editor-in-chief of The Carlat Child Psychiatry Report and co-author of the Child Medication Factbook for Psychiatric Practice, second edition, 2023.

MARA GOVERMAN: And I'm Mara Goverman, LCSW.  A licensed clinical social worker in Southern California with a private practice, and an avid reader of The Carlat Psychiatry Report.

JOSH FEDER: Over the years, in any child psychiatry career, somebody is going to run into a few of these things. I think in my career, I have run into more because I am old.

MARA GOVERMAN: Intriguing.

JOSH FEDER: But Mara and I together have worked with people with trisomy 21, and the issues that come up around treatment are really pretty interesting – and we have some other material and podcasts about that. But here we are going to be talking about when do you suspect something that necessarily is not obvious, as trisomy 21? So, what about these things you would otherwise not know? Because the kids who come to us are often ones who have seen a lot of other doctors, and people might not have thought to check for something that is not as clear.

MARA GOVERMAN: And not on their radar.

JOSH FEDER: Not on their radar. So, maybe they are having trouble, maybe they are on a bunch of different medicines, they have tried a bunch of different therapies, but nobody has ever gone back and asked, Is there some other developmental or genetic condition that is driving this that makes it harder to treat without usual approaches?

MARA GOVERMAN: And how do you begin to talk to the patient's parents and also develop a list of providers to get that information to help with diagnosis and treatment planning?

JOSH FEDER: In this podcast, we are going to be talking with Dr. Marilyn Jones. I interviewed her for a Q&A in The Carlat Child Psychiatry Report, and when we do that, we often cut down 10,000 words into 2,000, and you don't necessarily get the nuance and ambiance of the conversation. So, our hope is that in listening to this edited version of the interview – because we are cutting out a lot of "hems and hahs and you knows" – you too will get a feeling of what it's like to talk with Dr. Jones and learn a lot about how we as mental health providers can be a little bit more astute in thinking about these kinds of dysmorphological and genetic challenges. Dr. Jones, please introduce yourself and tell us about your background 

MARILYN JONES: So, I’m the Clinical Service Chief at Rady Children’s Hospital and Clinical Service Chief for Genetics. I’m at UCSD, a distinguished professor of pediatrics. I’ve been at UCSD and Rady since I finished my fellowship – before, I’m sure at least one of you was born! And so, I’ve seen this place grow and develop, and it’s been a cool ride. 

JOSH FEDER: That’s great! So, in your world, how often do people pick up on, recognize, and refer patients for dysmorphology assessment compared to what’s out there in the population? I guess I’m talking about pediatricians, psychiatrists, and other clinicians. 

MARILYN JONES: So, I get a lot of referrals from general pediatricians. I think it varies by the practice, and the nature of the patient that they’re seeing, and the confidence of the pediatricians. I will just say, I get very, very few primary referrals from psychiatry. Although, I have been asked occasionally to see someone on one of the inpatient units who is really having an acute episode. That actually is not the best time to do the kind of evaluation that I like to do because I like to get a lot of history, and I like to do it in a more relaxed setting than when a child’s having an acute episode. 

JOSH FEDER: Do you have any sense of what portion of the population has an identifiable problem, for which you would be the person who might be able to figure out what it is if people knew to send people to you?

MARILYN JONES: Well, the number that I use is that 3 to 4 percent of the general population has got some kind of a birth defect or congenital anomaly. I don’t know if you added behavior on top of that because those numbers weren’t generated, thinking in terms of behavioral challenges. But that’s a lot of kids. I mean, 4% of the general population is a lot of kids. 

JOSH FEDER: I guess the other question is how much of that is meaningful.

MARILYN JONES: I think most of that is meaningful. I think that 3% to 4% is a meaningful number. I mean, there’s another number that actually might be relevant to this. And this is a study actually that my husband has done – who works on fetal alcohol syndrome and alcohol-related neurodevelopmental problems. They have done a screening in the first grade in the San Diego public schools, and I think up to 5%* of the kids have had significant exposure to alcohol prenatally, which is a huge neurodevelopmental risk. 

JOSH FEDER: What are some of the more common conditions that clinicians might identify if they have more training?

MARILYN JONES: I think the single most common genetic disorder, which is about 1 in 5,000, is the 22q deletion syndrome, which I learned as DiGeorge syndrome, the official name of 22q deletion. It’s also called velocardiofacial syndrome. It’s got a lot of different names, but that’s one that psychiatrists particularly need to be aware of because about 20% of affected individuals are going to have some major psychiatric problem as they hit adolescence and young adulthood. (Botto LD et al, Pediatrics 2003;112(1):101–107; Provenzani U et al, Int Rev Psychiatry 2022;34(7–8):676–688)

JOSH FEDER: Are there some specific psychiatric problems...

MARILYN JONES: Schizophrenia is common. Depression and anxiety are pretty common.

JOSH FEDER: For instance, the rate of that population with schizophrenia would be far higher. 

MARILYN JONES: Oh, yes. It is a disorder that many families will know that, that’s what the diagnosis is because a chunk of those kids present with congenital heart malformations. And so, they will have had the diagnosis made because of the congenital anomalies that go along with this. But not every child who has this has a structural problem that would lead somebody to try to investigate the cause of that structural problem.

JOSH FEDER: In psychiatry, we might be seeing these people de novo if they hadn’t been previously identified; we’re assessing them for depression or perhaps psychosis, and we need to be thinking, Gee, is there some other kind of congenital condition that might be part of this? 

MARILYN JONES: Right. 

JOSH FEDER: Well, let me just take that a little bit further. So, what are we looking for in velocardiofacial syndrome?

MARILYN JONES: Some of the kids are a little bit on the small side, relative to their family. Many of them have had a variety of learning challenges. A lot of them have had speech therapy because of hypernasal speech. They talk like they have a cleft palate, even though they don’t have a structural problem in terms of the palate. Those would be tip-offs. Maybe there is an underlying condition that’s driving the neurobehavioral challenge the individual has.   They have a very recognizable face, but it’s a pretty subtle face,  it’s a trained person to see it, but you will sometimes recognize that the child doesn’t look exactly like their parents. 

JOSH FEDER: So, in terms of assessment for the general reader, having some guidelines that you might add to your usual assessment toolkit. Sounds like one of them would be Does the child look like their parents?

MARILYN JONES: Mmhm. 

JOSH FEDER: Are there other general guidelines that come to mind, in terms of having general people be more aware of the possibility of something going on? 

MARILYN JONES: Well, certainly a history of a congenital heart malformation. Certainly, a history of a cleft palate would be something to at least make you think about this diagnosis.  

JOSH FEDER: And what about more generally for the range of different diagnoses that people might identify? Like Fragile X or other things like that. Are there some general guidelines? If you were just going to teach a bunch of Med students how to be sharp, would you want them to be specifically kind of knowing about the specific conditions, maybe a few of them? And/or would there be some general guidelines for, just when you’re taking a history and doing an assessment, how to be sharper about this overall topic of dysmorphology?

MARILYN JONES: So, Fragile X, many of the affected males are going to have significant cognitive challenges, as well, and hopefully, would have been identified by that. The females who have this can have a much more subtle phenotype in terms of their learning challenges. But anxiety is a big piece of Fragile X. It is a recommendation of the American Academy of Pediatrics in terms of the workup of a child who has developmental challenges and/or autism to have Fragile X testing and a microarray, which is going to get the Fragile X diagnosis, is also going to get the 22q diagnoses. But it still amazes me how many kids have not had that workup.  

JOSH FEDER: Good point. And sometimes, we still have trouble getting it paid for, which is interesting, too. 

MARILYN JONES: Yep.

JOSH FEDER: Are there a couple of other kind of conditions that are towards the top of your list of things that people might want to be sure they know more about? 

MARILYN JONES: Well, alcohol-related neurodevelopmental problems would be on the top of my list. Because those kids have tremendous behavioral challenges with impulse control and sort of frontal lobe kinds of stuff, that makes them a huge challenge in terms of school, a huge challenge at home. And so, if I had to pick the top two things, that would be alcohol-related neurodevelopmental problems and 22q.

JOSH FEDER: Where would Fragile X fall? Further down?

MARILYN JONES: I think Fragile X would fall further down. I think one of the reasons that people spend so much time on Fragile X is that when you identify an individual who has Fragile X, that individual is usually attached to a family where there are multiple other individuals in the family who have it – or may be at risk. It really becomes a family-informing thing and a reproductive issue, particularly if a couple is interested in having more kids. So, we like to identify that diagnosis, so people are counseled relative to that reproductive risk. 

JOSH FEDER: Those are the top two – 22q and alcohol exposure. Are there any other conditions you would like us to be mentioning to people besides these? 

MARILYN JONES: I think you get into much rarer conditions. I think as a group, the next group of conditions that you might see are sex chromosome aneuploidy conditions. Again, there are many individuals who have these who never show up with medical problems at all. But, there are a group, a subpopulation, that have learning challenges and then behavioral issues that oftentimes I think are related to unsupported learning challenges that may end up with psychiatry. 

JOSH FEDER: To be clear, these are people who have XY plus another extra XY or... 

MARILYN JONES: Yeah. XY plus another Y; XY plus another X. A girl that has three X’s – those conditions.  

JOSH FEDER: I’ve had a couple of those kids come through my clinic over the years. 

MARILYN JONES: Yeah. And that’s common. Interestingly, we’re picking them up more now than we used to pick up because of the whole way we do prenatal genetic screening has changed. And people are now using free fetal DNA in the mother’s circulation because the placenta releases fetal DNA into the circulation and so, we are picking up Klinefelter syndrome. We are picking up Triple X prenatally when there’s no phenotype at all. And it’s going to be interesting to see whether or not that’s a population that just sails right through and they’re fine. Because we never would have picked them up, because we never did this kind of screening before, or whether or not it’s a population that you might end up seeing. 

JOSH FEDER: How does early identification, for instance, 22q, make a difference in the trajectory of the child’s development? And maybe it's not your area of expertise, but I’m just wondering what things people might do if they pick it up differently to try to help that child along. 

MARILYN JONES: There are a whole list of recommendations for a kid with 22q when they’re first seen because some of the kids have immunodeficiency, some of the kids have cardiac defects. So, you have to run, top to bottom, to be sure all the structure is okay. And then I would expect all of those kids to have some kind of a learning challenge. So, I get all of those kids into the infant education programs as soon as they’re identified so that when they go to school we’ve got a really good idea about what kinds of support they’re going to need, and to recognize that there is a high risk for problems with social interaction and those sorts of things, so that if you see a kid who’s got this diagnosis who’s struggling with peer interactions, for example, in elementary school, to see whether or not the school has a program or a little group that they do to help those kids with social interactions. So, you’re trying to support – so that you don’t let that fester unaddressed. 

JOSH FEDER: Got it. So, getting back to the screening and assessment, are you seeing that the majority of pregnant women are getting fetal DNA testing? 

MARILYN JONES: It’s the standard in California to offer it to all pregnant ladies. What used to be offered was serum screening, primarily for Down syndrome. That’s what I had years ago. Serum screening was a one-time thing in the second trimester for the last, I’d say 20 years. It’s been two blood draws – one in the first trimester and one in the second trimester but it’s all analyte-based screening. The state has switched about a year ago and it’s all free-fetal DNA. But, the state screens for Down syndrome, trisomy 18, and trisomy 13. You can add on sex chromosomal aneuploidy for a fee, and there are companies that will do 22q deletion and some other microdeletion syndromes prenatally, as well. It’s a screening test. It’s not a diagnostic test, but it’s a screening test that could then lead you to do a diagnostic test. Which, would either be a CVS or an amniocentesis to actually look at the genetic composition in fetal DNA. 

JOSH FEDER: That’s really helpful. That was going to be my next question, whether the rates of amnio rise or fall.

MARILYN JONES: They’ve gone way down because there are fewer false positives with this type of screening than there were with the analytes. So, the rate of diagnostic testing has gone way down. It’s interesting that we’ve actually looked at the rate of uptake of prenatal screening, and it’s about 70% to 75% of pregnant women will accept whatever the State is offering in terms of prenatal screening. And sometimes it's interesting that women– it’s supposed to be a discussion you have. But for some practices, this just goes with your prenatal labs. Here’s your lab slip. Go off and get it. And they don’t have any idea that they’ve just had genetic screening for Down syndrome.

JOSH FEDER: It's an interesting question. I work with a lot of people who talk about whether one should even ethically choose to have this, and you would think there would be a little bit of a discussion about it.

MARILYN JONES: I think that’s the 25% that do not uptake. They’re opting: No, I don’t want this information. I’m not going to act on it. I don’t need it. That’s absolutely a fair approach. 

JOSH FEDER: Are there differences based on social determinants, like people from lower socio-economic places or different racial or cultural groups that have less penetration of screening, but also of identification of these kind of conditions? 

MARILYN JONES: I don’t have those numbers right off the top of my head. I would bet there are differences that you could identify.

JOSH FEDER: Okay, are there other thoughts you have about – whether it's just a clinician in a clinic, whether it's a pediatrician, psychiatrist, or whatever other ways of thinking to sort of shift how we think about diagnosis, or whatever, to keep it top of mind so that people might be more likely to wonder or suspect. I think the big pearl so far that I have heard is that, Does the child – if it’s the child of two biological parents – look like their parents, are there others?

MARILYN JONES: If a kid has been struggling all along with learning challenges, developmental challenges, and now, there are behavioral things that are coming along, and it’s never been addressed in terms of, Why is this kid having so much trouble? When there’s no history of birth injury or meningitis or something that you can look back on and say, Okay, this is somehow related to the challenges that this child is having. I think those are the kids that need a little bit closer look. 

JOSH FEDER: That next look, is a CMA? 

MARILYN JONES: That’s where I start with a microarray. Microarray and Fragile X, very reasonable to do those things ahead of time; recognizing that one of the things with all genetic testing that you can get – it’s not always clean. It’s not just you get a positive result, you get a negative result. But you can get a variant of uncertain significance which can sometimes send people down a rabbit hole, and you need to warn people ahead of time that there are three results you can get: positive, negative, and a variant of uncertain significance that we will try to track down. 

JOSH FEDER: That's great, that’s what SPARK is for, right? 

MARILYN JONES: That’s part of what SPARK is for, yeah. 

JOSH FEDER: Do you want to describe briefly what SPARK is all about?  

MARILYN JONES: SPARK is where families can sort of sign up– if their kid has autism– they can provide a DNA sample, and it’s a system that uses huge numbers; and by using huge numbers, they’re hoping that the huge numbers will overwhelm the dirtiness of the data that’s there. 

JOSH FEDER: I did that with a drug study once. Where we tried to do that, and it was modestly effective in figuring out if whether antidepressants are helpful, it was fun. How do you talk with kids who are talking with you, and how do you talk with parents about these conditions when you’re meeting them? Or how do you recommend we talk with them about these things when we pick up on them or when we’re just suspecting? 

MARILYN JONES: For me, a lot of time I’m seeing the child when they’re young enough that I’m mostly talking to the parents. Although I do talk to a lot of adolescents who have got challenges about what’s there, and really, we just – the perspective that I take is that all of us have genetic differences. They just particularly have one that we know something about, that we happen to know about, and depending upon why they’re seeing me, it helps understand why they’re struggling with whatever it is that they’re struggling with, and it gives us a direction to go in terms of helping them. 

JOSH FEDER: Do you see issues with implicit bias that come in? I’ve been involved with some research, for instance, that showed that kids who–They looked at meconium, CP, T21, and something else I forget, and found that t21 and I think CP resulted in doctors talking to families in ways that would kind of gear them towards not having expectations or hopes of future function in a way that might limit the opportunity to even, try to give them opportunity so that they might achieve. Do you see anything about that with implicit bias surrounding this field in diagnosis? 

MARILYN JONES: I think that there’s tremendous bias. If you go back 40 years ago, people were told to put their kids with Down syndrome in institutions for the intellectually disabled. And I remember in medical school taking a field trip out to one of those places and being really overwhelmed with cottage after cottage of individuals with Down syndrome who were not doing much because there was no expectation. There was really little – they were sort of warehoused, and it was just incredibly sad. I don’t see that anymore. But I do see that there tends to be a sense that when you’ve learned about a condition that’s associated with severe intellectual disability and things that does oftentimes factor into, well, there’s nothing we can do here because you can’t fix the underlying chromosome problem. But it’s tremendously unfair to take away a family’s hope and limit a child’s future. Because the kids haven’t read the book about how it’s supposed to go, most of them make liars out of the doctors who talk to their families early on. And what it does, then, is that it makes the family so they never trust anything they hear from the medical profession again. 

JOSH FEDER: Do you have any thoughts about how to combat that kind of bias? Like, in our conversations with colleges and things like that, any buzz phrases?

MARILYN JONES: I don't know, that I have any buzz phrases relative to that. I clearly have changed the counseling that I do in the 45 years that I’ve been doing this. In the beginning, I tried to be honest with families about how things would go, and it didn’t feel right after a period of time to sort of, do that. 

JOSH FEDER: Are there any particular resources that we could share with clinicians, whether to help them bone up on this stuff, or guidelines or online sources, places that people can learn more or use for reference? 

MARILYN JONES: For specific disorders, people tend not to go to books anymore. Although, there is a book (conflict of interest) I was one of the authors on it – Recognizable Patterns of Human Malformation, that has like a one-page on like 300-400 different disorders with references and pictures so that it was designed to be used at the bedside for people to have a quick once-over, What’s this diagnosis and what do I need to know about it? For more in-depth discussion, many genetic orders have gene reviews online. And these are reviews that are written by experts in the field in a standard format, so that if you’re looking for What are the management things that I need to do for 22q deletion? You can go to the gene review and then scroll down to the management section, and see what’s there about that. They’re very well-referenced, and because they’re written in a structured format, I think they’re really easy to use. Many genetic diagnoses have parent support groups that are associated, and certainly, the active ones have superb content on them. And its superb content, that I think is hopefully presented because most of the families that are involved in that are pretty positive about their kids and what their kids are doing, and the kinds of challenges that they’ve had and the kinds of things that help. 

JOSH FEDER: Any last thoughts? 

MARILYN JONES: You were talking about stigma, and I think stigma is a huge problem. And I think it’s a huge problem relative to alcohol. I think women who drink during pregnancy are stigmatized, and their kids are horribly stigmatized, as well. So, it makes the disclosure of the information to get that history very difficult, particularly because I think what you were told is right. The minority of kids have physical findings that you’re going to be able to identify. A lot of them have these neurobehavioral challenges, the only way you’re going to get at that is with a history of exposure unless the psychologist who is testing them is savvy enough to recognize that the pattern of neurobehavioral problems that you see would point towards an alcohol-related injury. That was the stigma, and then the other point is that you were commenting early on facial recognition program, right? So, there is such a thing out there already, and it’s a program that’s called Face2Gene. It was developed, I believe, by an Israeli company where you can take a picture of an individual and upload it on their website, and they’ll give you a differential diagnosis of things. I use it; I will confess more recreationally, just to sort of see once I’ve got my idea about what I think is going on. I’ll say, Okay, what does Face2Gene have to say about it? But there are a lot of my colleagues that really find it tremendously helpful. 

JOSH FEDER: So, it’s not like ChatGPT where it makes stuff up? 

MARILYN JONES: No! It doesn’t make stuff up. It's not artificial intelligence that makes stuff up. It’s facial recognition software. 

JOSH FEDER: I really enjoyed listening to this interview again. And especially how it talks about what we can do and how we can talk to families about these conditions. So, I really appreciate the opportunity to take a look back and do this today. We hope you enjoyed today’s Podcast. You can read more about Dysmorphology and Common Developmental Disorders in Children and Adolescents in our January/February/March Newsletter. Hopefully, people will check it out. 

MARA GOVERMAN: Everything from Carlat Publishing is independently researched and produced. There’s no funding from the pharmaceutical industry.   

JOSH FEDER: Yes, the newsletters and books we produce depend entirely on reader support. There are no ads, and our authors don’t receive industry funding. That helps us to bring you unbiased information you can trust.

MARA GOVERMAN: As always, thanks for listening, and have a great day!