Undiagnosed Disease Network
Nearly two years ago we applied to have Lydia seen by the Undiagnosed Disease Network (UDN). It is a nationally funded program that supports seven clinic sites across the US to study mystery medical cases like Lydia’s. You have to have had a lot of inconclusive tests and baffled many specialists for them to accept you into the program. They study unicorns. You also have to be able to organize all your information, and this is the part that nearly defeated our application. We had seen so many different doctors and visited so many hospitals… I have two big file boxes of paper records. But the UDN helped us with this too. They paid for a one-time records collection to be organized conveniently online through a website called Picnic Health. It got us through the last hoop and we were in!
Last February, arrangements were made and the UDN flew my whole family out (Mark, the kids and I) to see a team of medical researchers at their Stanford University site in California. I was reluctant to involve Jack as I prefer to keep him from seeing the intensity of Lydia’s medical life as much as possible, but it ended up being like a cozy clinic rather than a hospital, and the doctors were at their leisure to spend plenty of time talking with us. Nurses brought us snacks and Jack played the iPad during his blood draw, hardly looking up. We were very comfortable. We even had a thoughtful care coordinator who made sure we got the hotel okay and that all our questions were answered. I’d been anxious that the trip might cause flashbacks of our early, terrifying days at the hospital, but instead we had lunch in the sunshine at a café on campus, and admired the lush plant life of California between appointments.
They took blood and urine samples from us all, and a skin sample from Lydia that will leave a small scar. They looked at Lydia’s features, trying to decide if she had “tapered fingers, curved toes or epicanthal eye folds.” They asked for our story again and reviewed all the possible diagnosis she’d been given. In the end, no conclusion were reached during our visit. They will spend the next months combing through her genetic testing results to see if they can find something that’s been missed. I feel relieved to be able to let go of the reigns on this one a bit, let someone else worry about it.
But there was one bit of information from the neurologist that only recently sank in. He said that her loss of white matter, i.e. leukodystrophy, was not what he considered her primary symptom. He said it was Early Infantile Epileptic Encephalopathy (EIEE). At the time, I brushed this off because it didn’t mean anything to me. But recently I stumbled into a realization – EIEE is also called Ohtahara Syndrome. I knew this at some point but had forgotten about it. Lydia has had EIEE on her file since the beginning, and the very first test she had four years ago was the genetic panel to look at variants that cause EIEE. It came back negative, and I had crossed it off at the time. But the UDN doctor pointed out she still has the primary symptoms and they are discovering new genes all the time. He helped us see what Lydia has been dealing with from the beginning, EIEE or Ohtahara Syndrome.
Of course I immediately found and joined the Ohtahara Syndrome Facebook group and started pouring over the posts. What I saw took my breath away. The kids on there are JUST LIKE LYDIA! Intractable seizures, non-verbal, non-mobile, also totally adorable…some of them even have low white matter like Lydia. But I feel confused – why did it take me so long to find this group? The challenge of being undiagnosed is at best frustrating and at worst terribly isolating. I deeply depend on my cerebral palsy community, but their kids often seem to make progress in ways that we can’t relate to or even hope for. The leukodystrophy group never quite matched for Lydia either in that their kids seemed to get different, more definite information from doctors. They might not even have seizures. Lydia just never fit. We’ve always felt very alone when it comes to answers. So it is both relieving and confusing to feel like there has been a sort of answer right under our noses this whole time. I say “sort of” because Ohtahara Syndrome might be considered as more of a broad grouping of symptoms rather than a syndrome unto itself. But I guess for now we will say this is what Lydia is dealing with. This may still change if the UDN discovers more information, and it is an anti-climactic pause in a diagnostic legacy, but for now we will let it quiet the question we’ve been hauling around for four years. Lydia has Ohtahara Syndrome. Bewildering.
- Seen in infancy, usually before 3 months. (Lydia started having seizures at about 3 1/2 months)
- Usually tonic seizures lasting seconds, singly or in clusters. Spasms typically last up to 10 seconds, and can occur hundreds of times per day. (Exactly how Lydia’s seizures are and unlike any other diagnosis we’ve pursued)
- Very resistant to seizure medications. (Lydia, yes)
- Often caused by brain malformation or metabolic disorder, especially where the cerebral hemispheres do not develop fully and or there is an agenesis of the corpus callosum. (Lydia yes, plus the low white matter that other Ohtahara syndrome kids seem to have)
- Cases have been reported in which the early myoclonic encephalopathy worsened after an administration of vigabatrin. (This is the only drug that caused a strange reaction in Lydia)
- Ohtahara syndrome can transition into West syndrome over time, and can further evolve into Lennox-Gastaut syndrome. (Lydia, possibly)
- Some genes that have been associated with OS include ARX, CDKL5, SLC25A22, STXBP1, SPTAN1, KCNQ2, ARHGEF9, PCDH19, PNKP, SCN2A, PLCB1, SCN8A, ST3GAL3, TBC1D24, and BRAT1. (Lydia, no. We have not found any variants of known significance . . . yet)
- EEG has a burst suppression pattern. (Lydia, no. She has Hypsarrythmia on her EEGs. Maybe this is why no one explicitly directed us towards Ohtahara?)
- Other syndromes in this group include West syndrome, Dravet syndrome, Lennox-Gastaut syndrome, Landau-Kleffner syndrome, and electrical status epilepticus during sleep. (Some of these have been suggested for Lydia before)