Mike is the Managing Director of SRF. His son Tony was diagnosed in 2018.
When families are first diagnosed with SYNGAP1 and come to me in search of answers, I begin by congratulating them on receiving a diagnosis. They look at me with some justified confusion since they just found out their child has a genetic disease for which there is currently no available treatment. Why am I congratulating them? While thousands are still searching for answers, they are some of the ~800+ patients who’ve been given clarity, making the genetic report they’ve just received a precious compass, pointing them towards communities of similar patients & genetic therapies that SRF are tracking and supporting, while paving the way towards better understanding the challenges their loved one is facing.
When you have a child with a rare disease, you can’t have too many friends
If you are lucky enough to secure an appointment with a geneticist and/or genetic counselor after you are diagnosed with SYNGAP1, here’s how to prepare and make best use of the time. Like with all clinicians, this first meeting is the beginning of a relationship between you and someone who will be taking care of your loved one with SYNGAP1. Think of this as the beginning of an invaluable relationship, not just another appointment with another provider.
Relationships go both ways. A geneticist can help you understand your loved one’s rare disease and can connect you to other clinicians & researchers. You can help them understand the reality of SYNGAP1 and share information with them that you have learned from the patient community. If there is a group that has been helpful to you — like SynGAP Research Fund — tell them, so they know who to send their next patients to.
What is the difference between a geneticist and a genetic counselor?
A medical geneticist refers to a physician (MD or DO) who has completed a residency or fellowship in genetics (and often some other specialty – most commonly pediatrics). Their training supports the recognition and diagnosis of disorders with a possible genetic cause as well as the management of those individuals post-diagnosis.
A “geneticist” can refer to a laboratory geneticist who has completed a PhD and a fellowship in the interpretation of genetic testing. These are the folks signing off on genetic test reports and patients are less likely to come across them. The broad term geneticist can also be used by a scientist who studies genetics.
Genetic counselors have received graduate training (masters degree) that focuses on the interpretation of genetic testing and supports families in understanding and adapting to that information. Genetic counselors are often partnered with a physician (geneticist, neurologist, cardiologist) but may also see patients independently.
SRF has both an exceptional medical geneticist & genetic counselor on our Scientific Advisory Board (SAB): Dr. Heather Mefford MD. PhD did an outstanding webinar for SRF; it’s worth watching before you see your geneticist, and you may even want to tell them about it. Elise Brimble, CGC has helped diagnose a SYNGAP1 VUS patient (case study) and now leads the Clinical Operations team at Ciitizen, which is SRF’s partner for our digital Natural History Study. See her webinar on Ciitizen here.
How do I prepare for this meeting?
- Read the existing articles from SRF linked below.
- Know the address(es) of your variant(s) Most variants have both a c. and p. address, they are two ways to describe the same thing. Think of it as a street address and GPS coordinates for the same house. There is important information in these addresses and it is good to have it explained. Can’t wait? Read this blog post to learn about the meanings: Understanding your genetic report with SYNGAP1
- Know the classification of your variant(s) Each variant has a classification from 1 to 5, from pathogenic to benign. These reflect the scientific community’s current understanding of whether that variant causes disease, using information from medicine, biology and computer modeling.
- Bring a notebook.
How many variants do you have?
If you have multiple variants on your genetic report, start there. You should ask about the classification of each and what the geneticist thinks of this. What are the odds of the classification changing? For any variants listed as benign, it’s important to understand why. Which tests have been performed to date? Are any more tests indicated, for the patient or parents? Be sure to ask how certain they are that the SYNGAP1 mutation is causing the symptoms you are seeing.
Specific questions to ask about your SYNGAP1 mutation
If your variant is currently classified as a VUS:
- A VUS means the scientific community is not yet sure of the effects. This could mean there are more tests you can do now to understand if this mutation is disease-causing. For intronic mutations you should ask for RNA sequencing to understand the impact of the mutation.
- For missense mutations you should explore building an iPSC for the mutation if it doesn’t already exist. As long as you have a VUS, you should follow up annually with the geneticist and testing company to see if the classification of the variant has changed. You should also ask all the questions below for P/LP mutations.
If your mutation is “Pathogenic” (aka Level 1) or “Likely Pathogenic” (aka Level 2), then ask these questions:
- What does every single letter, number & symbol mean in the genetic report of the variant
- How far from therapies are we? Which kind of therapies will this kind of mutation be amenable to?
- How many other patients have this mutation? We find that connecting families with the same variant is usually helpful.
- Who are the best local clinicians for kids with complex genetic epilepsies/neuro developmental disorders?
- What is new in the literature that impacts our situation?
- I would like to come back in two years to find out how the field has changed.
- Have you heard about Ciitizen, there are over 100 patients signed up with de-identified data available for research. If you are interested, please contact SRF!
The field of genetics has been evolving quickly over the last 20 years. Every few years have seen advances in the clinical tests available, and the price of tests has often decreased dramatically. The amount of population information, knowledge about the specific sequence variation in specific people, is gathering at an astounding rate. Researchers use bioinformatics to assess that information, with continuous updates to databases. Add to that the large number of precision medicine treatments in development, and the landscape is constantly changing for our loved ones with SYNGAP1. Seeing a geneticist once gives you information that is available at that time. A few years later, the recommended steps might have evolved. The relationship you have with a geneticist and genetic counselor is important and likely to be ongoing over decades.