What's the matter with Kate? My husband and I never had an easy answer. Our only child had her first tonic-clonic seizure (a type of seizure that involves loss of consciousness and violent muscle contractions) in 1989, just before she turned 1. A cluster of seizures a few days later landed her in the hospital. An EEG and MRI were normal, and her seizures were deemed “idiopathic,” meaning the cause was unknown. She was released and sent home with a prescription for phenobarbital.
Around this time I noticed that her wet diapers had a maple sugar scent, which I knew from my reading and research could be a sign of a genetic disorder. When I mentioned this to her pediatrician, he referred us to the local children's hospital, where tests ruled out maple sugar urine disease. Her doctors explored other possibilities based on unusual amounts of some compounds in her blood and urine. The findings identified only a minor impairment in metabolism of the fat palmitate, suggesting a problem with fatty acid and perhaps energy metabolism.
Kate's seizures increased in frequency and type. New technology gave her doctors other options. They did a functional MRI of her brain and a spinal tap to assess amino acid levels in cerebrospinal fluid. Their prevailing theories went from an inborn error of metabolism to her symptoms being the result of several gene variants working together. At one point her doctors said maybe she just had “Kate Dolan disease,” a condition unique to her.
Our daughter had multiple seizure types, as confirmed by her doctors and EEG tests, but she was most affected by ones that initially caused rhythmic flapping of both arms over her head and later involved her legs, which led to frequent falls. She took multiple antiseizure drugs and, to help short-circuit seizures, had a device implanted to stimulate the vagus nerve to the brain.
Despite her challenges—uncontrolled seizures, poor muscle tone, and some intellectual disability—Kate grew up to be friendly, positive, and hardworking, all of which helped her eventually graduate from college. After graduation, she lived independently and worked in childcare, which she loved.
Once genetic testing became more available in 2014—the year Kate turned 26—her doctors ordered two genetic screening panels: one for variants known to be associated with epilepsy and one for mitochondrial disorders. Neither one revealed the cause of Kate's condition. By 2017, genetic screening technologies had become more sophisticated. A blood test revealed a potential clue—a variant of “unknown significance” in a gene called CSNK2b.
Kate died in 2019 of sudden unexpected death in epilepsy (SUDEP). She never learned what was wrong with her. After an autopsy, we were contacted by her genetic counselor in 2020 and notified that Kate had CSNK2b deficiency, also known as Poirier-Bienvenu neurodevelopmental syndrome, named after the researchers who first described the condition in 2017. We also learned that the gene variant arose spontaneously in Kate. Fewer than 100 cases are known globally, but increased genetic testing of younger patients is revealing new ones.
Although Kate did not benefit from this knowledge, others have. I have connected with an amazing group of parents of children with the condition from around the world through a CSNK2b Facebook group. They have been eager to learn about Kate and her challenges and how she overcame them.
Our CSNK2b community plans to establish a foundation to encourage research into treatments and to provide support for patients and families. Although there are not yet definitive treatment options, a diagnosis does make it easier to receive educational support and to qualify for government services and benefits.
What was the matter with Kate? We have an answer now and can turn the question into a declarative statement: Kate had Poirier-Bienvenu neurodevelopmental syndrome. Our knowing that has allowed her legacy to live on.
Rebecca Dolan, a botanist, and her husband, Tom, a mycologist, are retired from Butler University in Indianapolis. The Dolans split their time between Indianapolis and St. George Island in Florida, where they enjoy fishing and exploring the natural world.
