At the National Society for Genetic Counselors Annual Conference, I had the chance to sit down with Kelly Minks, MS, CGC. Ms. Minks is a genetic counselor in the Department of Neurology at the University of Rochester Medical Center, with a clinical practice focused on pediatric neurology. She routinely orders exome testing for children with developmental disorders and epilepsy. 

Meg: Why is proactive analysis through Patient for Life important for you and for your patients? 

Kelly: Many of our patients are medically complex. Patients often see many different specialists and receive many different therapies like occupational, physical and speech therapy, both at home and in their school setting. They have a lot on their plate. When we get a negative result on exome and ask them to schedule an appointment with us in two to three years to consider reanalysis, that really puts a burden on that family to have to remember to schedule the appointment years down the road. 

As a provider, it's important to us because we don't have a mechanism at our institution to be able to call families in two or three years and remind them to schedule a follow-up appointment. Proactive reanalysis relieves that burden for us too. Knowing that it is happening in the background prevents people from slipping through the cracks in that process. It’s also, of course, really reassuring to families to know that when we get a negative result on exome, it doesn’t mean that we're done, or that we're done looking. I can at least tell them that while we didn't find an answer today, Ambry will keep looking, they'll automatically update us, and issue an amended report if we find something informative. 

Meg: Can you describe the experience of contacting patients with an answer from proactive reanalysis? What is that phone call like? 

Kelly: I really try to prepare patients for the potential of that call during their pretest counseling visit. I discuss the possible results we can get back from exome, including a negative or uninformative result. I explain to patients that Ambry will continue to look for new gene-disease associations and they'll automatically update us when and if they find something. 

I have had a handful of cases over the years where I did receive a positive exome result back from the proactive analysis. All the families are surprised to hear from me, especially when it’s been several years since we saw them, but they're really all grateful for the information. 

Meg: We’ve heard some genetic counselors express concern about reaching a family that might have moved or changed phone numbers. Has that happened to you? 

Kelly: I have heard that same concern from other people: what if we can't get a hold of a family after several years? While I haven’t had that happen yet, we do have many alternate ways of contacting families. We can contact them through their pediatrician, other health care providers, or their listed emergency contact numbers. We’re in a profession where we're trained to build rapport, even during conversations that are unexpected and difficult, so I don’t think we shouldn’t shy away from them for that reason. 

Meg: Can you share an example of recontact? Do you have a case in mind? 

Kelly: I do. I have a really good case that had a follow up recently. Let me provide a little background about this case, which started in 2017. We saw an 11-year-old girl in our pediatric neurogenetics clinic for progressive spasticity and weakness in her lower extremities. She clinically fit with a progressive spastic paraplegia phenotype. Her family history was negative, and she had a negative workup for acquired and treatable causes, including a brain MRI. We decided to start with a hereditary spastic paraplegia gene panel, which was negative. From there, we decided to move on to whole exome sequencing, and also got a negative result. I discussed the Patient for Life program with the family as part of our results discussion. 

Then, in 2021, we received an amended report from Ambry through the Patient for Life program. The family had not followed up with us, so we would not have sent a request for reanalysis. We got it automatically. It showed two variants in the HPDL gene. One was a pathogenic variant, and one was a variant of uncertain significance, and they were inherited in trans. 

We know that biallelic pathogenic variants in HPDL cause a variable phenotype that ranges from a juvenile-onset pure hereditary spastic paraplegia to a later-onset spastic tetraplegia, and often with developmental delay and other associated neurological features. Clinically, we felt that she fit with the juvenile-onset pure hereditary spastic paraplegia phenotype, so we considered these findings compelling and likely diagnostic. 

I called the family and learned that they had moved out of state, which was why they had not followed up with us. They were, of course, surprised to hear from me after four years, but they had not pursued any additional genetic testing since they had left, and they were very grateful to receive a result. They had gone through years and years of wondering what the diagnosis was and how she would do as she grew. We were also able to provide some prognostic information, including that we would not expect to see her develop additional neurologic features. They 
were just grateful to receive a diagnosis and to also better understand the recurrence risk in the family. 

I just called them again a couple of months ago after I received a letter from Ambry about a natural history study for HPDL that had the potential for a clinical trial. This patient fits criteria and may be a good candidate for the study. And again, this wasn't provider driven. This was an automatic letter from Ambry giving us the information about this natural history study and trial. Again, they were surprised to hear from me, but they were super excited. They reached out to the coordinator and are going to discuss the trial. 

Meg: What advice do you have for genetic counselors as they choose a lab partner? 

Kelly: We know that we have a lot of good options. I think it's important to find the balance between what we need as a genetic counselor and what our patient needs. As a genetic counselor, we need a reliable lab. We need a lab with a lot of experience. We need a lab with a good product. We need a lab with good customer service. And for patients, we want them to have a good billing process and easy ordering process. 

I would encourage genetic counselors choosing a lab to ask questions about the lab’s bioinformatics pipeline, their reporting, whether they include family members samples in their analysis, and I would encourage them to ask about the reanalysis process: how many times is that available? Is it free or is there a charge? Is it provider-driven or is it automatic? How do labs handle amended reports? When deciding between good labs, some of these factors start to really matter. 

Meg: That’s great advice, Kelly. Thank you so much for sharing your experience with me. 

Kelly: Thanks for having me.