The link between seizures and the Tuberous Sclerosis Complex

Margaret Cox believes it was more than a coincidence when UAB and Children's Hospital opened a clinic to manage tuberous sclerosis complex the same month that her baby boy was diagnosed with the rare genetic disorder.

"It was such a blessing from God," Cox said. "All this fell into place."

The clinic, started last April, serves patients from throughout the Southeast the second Tuesday of each month. With its specialists and patients, the clinic has made Birmingham a hub of work involving tuberous sclerosis complex, more commonly known as TSC.

The complex causes tumor-like growths called tubers. These growths can affect the skin and internal organs, and can be life-threatening when found in the kidneys, heart and lungs. TSC often affects the brain, and can cause seizures, mental retardation or autism. It occurs in about 1-in-6,000 births, and it can be inherited or caused by a spontaneous genetic mutation.

Cox said there was no hint of problems when her son Michael was born. Then, when he was 8 weeks old, his hands started shaking and twitching. Cox videotaped the incidents and took Michael to the pediatrician. He was referred to Children's Hospital, and his shaking was diagnosed as seizures. Further testing revealed tubers in his brain, and a genetic test confirmed it was TSC.
It was a disorder that Cox had never heard of, but her husband and Michael's father, Dr. Jared Cox, knew a little about it.

He had just finished medical school and is now a resident in urology at UAB.

With the new TSC clinic opening, the Cox family had a place to go for specialized care. Dr. Martina Bebin, a neurologist, said the clinic is staffed by herself; Dr. Bruce Korf, chair of the UAB Department of Genetics; and Dr. Amy Theos, director of pediatric dermatology at Children's Hospital.

So far the clinic has had about 70 patients from throughout the Southeast, and many of them had never seen a specialist for their conditions, Bebin said. With proper care, a person with TSC can have a normal life span, but the condition sometimes requires careful management.

For instance, Michael is given three medications daily to control his seizures. His mother said the medications work well, but as Michael grows they have to be continually adjusted. "It's a constant balancing act," she said.

The clinic also sparked creation of a chapter of the Tuberous Sclerosis Alliance. Carole Pitard of Mountain Brook, co-chair of the chapter, said the group provides support, education materials and research funding. It also raises awareness about the condition.

"So many people are not aware of TS," she said.

The alliance has planned a fundraising walk Saturday, April 5, entitled "Step Forward to Cure Tuberous Sclerosis Complex." For more information, go to www.stepforwardtocuretsc.org.
Korf, a national authority on medical genetics, said two genes have been associated with TSC, and mutation of either can lead to the disorder.

The genes hold codes for the production of two proteins, hamartin and tuberin, he said. These proteins are involved with cell growth and differentiation. Given the increasing knowledge of genetics, researchers are working on new treatments that go beyond managing symptoms, he said.

"The overall goal of research ... is to develop treatments for the condition based on underlying genetic mechanisms of the disease," he said. "There already have been some clinical trials, and we expect that the pace of developments of new candidates for treatment will increase as more is learned."