Fresh from a mission to India, UC Davis MIND Institute researcher and 2017 Emil M. Mrak International Award recipient Randi Hagerman, M.D., discusses her work sharing best practices for neurodevelopmental disorders worldwide — and how cultural and social norms come into play.
After visits to more than 20 nations to research, treat and educate about neurodevelopmental disorders – and more in the works – it’s not hard to imagine why the UC Davis Cal Aggie Alumni Association honored Randi Hagerman, M.D., with its Emil M. Mrak International Award in February for the extent of her dedication to the field.
After graduating valedictorian from the UC Davis College of Letters and Science in 1971, Hagerman (née Jenssen) went on to a career as a developmental and behavioral pediatrician. She’s since become an internationally recognized neurodevelopmental clinician and researcher, especially for her work on fragile X, the most common known genetic or inherited cause of autism and other intellectual disabilities.
Hagerman helped found the National Fragile X Foundation in 1984 – an organization that now spans 22 countries – and later became an endowed professor and chair in fragile X research at the UC Davis MIND Institute. In 2001 she first identified FXTAS, another member of the family of Fragile X-associated disorders, with her husband and fellow MIND Institute researcher Paul Hagerman, M.D., Ph.D.
Today Randi Hagerman is the MIND Institute’s medical director and also leads its International Training Program in Neurodevelopmental Disorders (ITPND), a program she spearheaded to educate health care professionals worldwide in the study, evaluation, treatment and management of neurodevelopmental conditions such as fragile X syndrome, autism, Down syndrome and ADHD.
An estimated 300 million individuals globally have a neurodevelopmental disorder, but only a small percentage of health care professionals are familiar with these conditions, and still fewer expert in their treatment and management. It’s a tremendous opportunity to make a difference – that also comes with tremendous challenges. In addition to language barriers, Hagerman and colleagues also navigate cultural differences regarding prenatal counseling and genetic testing, government-imposed birth limits, arranged marriages, and even prescription medication.
Hagerman recently recounted a nine-day trip to India to provide a snapshot of the work. Two ITPND program’s international scholars joined her in the conversation: Wilmar Saldarriaga G., M.D., M.S.C., a Colombian obstetrician specializing in embryology and genetics, and Xianlai “Dean” Duan, M.D., a Chinese neurologist. Both have studied and published on fragile X in their home nations, and through the MIND program work to develop knowledge and skills in neurodevelopmental intervention that they can employ and share in the future. Excerpts:
Q. Dr. Hagerman, you just returned (last night!) from a trip to India with the MIND Institute’s international training program. What were you up to there?
A. We did quite a lot. We were in Delhi first, speaking to members of the Indian Pediatric Association and sharing information with influential pediatricians about how to diagnose autism, who to test for fragile X syndrome, and new treatments for both disorders. We’re going to help them put together guidelines for fragile X testing in conjunction with India’s Fragile X Society, which invited us. In Bangalore we set up collaborations with key fragile X researchers from the National Institute for the Study of Biological Sciences and spoke at a hospital. We spoke at hospitals in Calcutta and saw some patients with fragile X syndrome, and also spoke at hospitals in Mumbai where we also saw patients with the local doctors there to give advice regarding treatment.
Q. That’s a lot of ground to cover in a week.
A. We were able to visit all of the big cities and share information about awareness and about establishing new criteria for diagnosis and treatment. We feel the visit and the follow up is going to dramatically increase awareness of fragile X syndrome, autism and fragile X-associated disorders there and help to guide screening and treatment by pediatricians, particularly developmental and behavioral pediatricians. They use some medications there but not very many, so we talked about new targeted treatments for fragile X and autism and feel it will really help to establish them as well.
They’re also very interested in new research, and the Fragile X Society of India has committed to funding at least one scholar per year in our international training program here at the MIND Institute, similar to the roles of Drs. Saldarriaga and Duan.
In all it’s a wonderful collaboration and we really feel the work will help to train more people in India to give optimal therapy for fragile X and autism, behavioral interventions, medication interventions and all kinds of other things.
Q. What’s the state of the union in India in regard to neurodevelopmental disorders? What do we know, and how typical is the state of our knowledge?
A. We don’t know the fragile X syndrome prevalence in India – it may be it’s more prevalent in some areas than others. Our scholars in Colombia, South America, have done more studies there and know that it’s very prevalent there. In certain parts of China it may be fairly prevalent, but in others not so much. But in all of these areas, autism is pretty high.
Building awareness is just so important. We’ve met families who believed that meningitis was causing health disturbances for their family members when it was really fragile X syndrome. Fragile X doesn’t just cause intellectual disability or autism in children – carriers can also have problems such as early ovarian failure, tremors and movement problems from the fragile X-associated tremor ataxia syndrome (FXTAS), hypertension, migraines, hypothyroidism, depression and anxiety. There are many symptoms we want to treat, and we also want to help prevent the related late-onset neurological problems of FXTAS.
Q. How do cultural differences come into play in this overseas work?
A. Taking India as an example, there were a lot of differences to navigate. First the concept of carriers, and identifying siblings or other individuals in the family who are carriers, is very difficult there, and it limits the genetic testing and counseling you can do. I saw a lot of children with fragile X syndrome, and in many cases you can’t tell people outright that mom’s a carrier because everybody’s afraid of the social consequences. The thought is if you say mom’s the carrier at the time of diagnosis, then the mother could be abused for causing the problem. As a visitor these things are awkward and painful to think about, but they’re there and they have to be considered. (Editor’s note: In 2012 a Thompson-Reuters affiliate’s poll of 370 gender specialists worldwide identified India as the worst place to be a woman out of the G20 countries, and Unicef research found more than half of adolescent boys and girls believed it was justifiable for a man to beat his wife.) Arranged marriages can also be disrupted if someone is known to be a carrier. Testing can have such severe cultural connotations that you have to introduce that concept more slowly over time and once you know the family better and the consequences of this knowledge.
Another big difference is there’s no mandated special education in Indian schools. Speech and language therapy happens in clinics because infrastructure in the schools is very limited. A lot of the therapy needs falls on developmental centers or private organizations, and that’s hard because a lot of families don’t have the resources to pay for that therapy.
Q. How do you work with situations like these, and troubleshoot?
A. You have to be guided by the physicians locally about how to handle the cultural differences, although at the same time you’re dealing with differences in the medical culture as well.
For example, Indian physicians often don’t use psychotropic medication. And so you have a child that’s out of control and might respond well to a specific reuptake inhibitor or another targeted treatment, but physicians don’t know how to do that. And there are very few geneticists there. So our focus was on training pediatricians and we gave a lot of talks to them. The message we sent out is that it’s up to the pediatricians to order the blood tests and make the diagnoses, because they can’t refer to a geneticist – it could take a couple of years to see one. We want to empower the pediatricians, and we’re going to work with the Indian Association of Pediatrics to help put together the standards for diagnosis and treatment for individuals with fragile X syndrome and autism.
So there are some cultural things that are easily changed, like the use of targeted pharmaceutical treatments to help reverse abnormalities and improve behavior. And there are other things culturally that we can’t change or that you have to be very careful with, like cascade genetic testing.
Q. So in your toolkit from our culture you have a range of diagnostic and therapeutic options, and when you come into these different cultural settings you have to pick and choose carefully which to apply. You can’t use them all – but you can still help?
A. Absolutely. Another part of the difficulty is some centers don’t know how to do DNA testing for fragile X, for instance, so we’re helping them do it. It’s also expensive for many families, so we’re setting up a collaboration with a scientist at the National Centre for Biological Sciences in Bangalore to learn how. He’s willing to screen a significant number of patients who are at risk for fragile X.
So we were trying to improve the diagnostic expertise of a number of centers and help more people get identified with fragile X, because families struggle so much with out- of-control kids, and don’t have as much support through therapists. The medical or psychopharmacological intervention can be very helpful to these families. It’s not too much different than in China and Colombia. A lot of countries have the same challenges.
Q. Drs. Saldarriaga and Duan, what’s it like translating approaches from one culture to those of your home nations?
A. (Wilmar Saldarriaga): The knowledge is the same. Take the medications – the physicians like me often have resistance initially. But after time, they’re more accepting. Usually the physicians don’t prescribe psychotropic medicines for boys, but after they receive the scientific information they will prescribe. After that the challenge is then with the family – depending on socioeconomic status, the family may accept the medicine but not give it to the child. This is a cultural problem. But with time and education it’s possible to get a good result and good integration. Perseverance is important.
Q. Dr. Duan, how important is this work in China?
A. (Xianlai Duan): China of course has a huge population and many people may have fragile X syndrome. Diagnostics are still a question. Many doctors have never heard of the syndrome or disease, and there’s no medicine or therapy. We need to do more for the people, especially rehabilitation.
Q. What kind of responses do the MIND Institute’s international program scholars receive when they publish in their home nations?
A. (Randi Hagerman): As one example, Dr. Duan’s papers are just beginning to increase awareness among physicians in China. But we’re talking about a heavy educational emphasis for physicians regarding diagnosis and treatment. It takes a while to change the ways physicians do things. It’s not easy. Every day I was in India I spoke with many physicians through lectures and individually, and we saw patients with physicians and suggested treatment approaches and gave opinions on probable diagnoses. And we found that they just weren’t aware of these things.
Q. How do you feel about the impact of the MIND Institute’s international training program so far?
A. (Randi Hagerman): We feel we’re changing the world by improving treatments, diagnostic standards and awareness. We’re honored to be writing new standards of care with the Indian Association of Pediatrics. The Fragile X Society there was so appreciative that we could meet with key pediatricians throughout their country.
You see, families are well educated now. They can read about these treatments on the internet. So they’re demanding that their physicians get up to speed. We met with many physicians, and of course some are much more amenable to new standards than others. A lot depends on the age. But sharing information on issues like diagnostic criteria and health care policy can really help to get many more people diagnosed and treated.