That was the day, when the little girl was just turning 1, that her mother, MaryJane, noticed the baby’s neck jerking oddly. By the third time it happened, even the baby’s laid-back father, Chris, became alarmed.
Four days later, they got the diagnosis: a disease called tuberous sclerosis, at the time — 20 years ago — a poorly understood syndrome with even poorer treatment options.
“Then, there was no way of knowing how people got the disorder,” says MaryJane.
But two weeks later, the Mudds met someone who for decades would change and brighten their lives, not only as a physician but as a friend. Or, as MaryJane puts it, “In walks Hope Northrup.”
Northrup, a clinical geneticist with the University of Texas Health Science Center at Houston, had made a specialty of studying tuberous sclerosis, a disorder that causes benign tumors to grow on vital organs. (Northrup, along with Mary Kay Koenig, a pediatric neurologist, runs a Tuberous Sclerosis Center at UTHealth, one of only 20 in the nation.) In severe cases, it can lead to autism, intellectual disability, epilepsy and a host of other problems. In mild cases, it may present itself at middle age, when tumors appear.
But over the past 20 years, progress has been made in treating patients like Mackenzie with new drugs and identifying children with the disease more quickly. In some cases, it can be diagnosed in utero. There is, however, no cure.
Mackenzie suffered the full array of difficulties, including seizures that were nearly impossible to control.
The Mudds wanted to have another child, but because they didn’t know how tuberous sclerosis was passed to the child, they were reluctant. Then researchers found a gene mutation that seemed to cause the disease, at least in many cases. Northrup urged the couple to have another baby.
“On a wing and a prayer, and with tremendous encouragement, we had one more child,” says MaryJane. Juliette was born in 1996. “I spent the whole first year just staring at her,” says Mary-Jane.
Two gene mutations
Shortly thereafter, a second gene mutation was discovered. Neither of the Mudd parents had either mutation. Enter Karenna, born in 2000.
The family’s experience was fairly typical. About two-thirds of cases of tuberous sclerosis are the result of spontaneous mutation. The other third of patients inherit the mutation from a parent who has a mild case of the disorder.
The genes, known as TSC-1 and TSC-2, reside in every cell in the body from conception, and in non-mutated form control a cell’s growth. The mutated form causes a loss of that control. Tumors can form on the brain, kidneys, eyes, lungs and heart. In addition, facial angiofibroma, or tiny BB-like tumors under the skin of the face — singularly disfiguring — are characteristic.
As common as Marfan
Tuberous sclerosis is little-known outside its small circle of patients and families, but it is not exceedingly rare. Northrup says incidences range from 1 in 6,000 to 1 in 10,000. She estimates 1,000 people in greater Houston have it. It’s about the same instance as Mar-fan syndrome, a disease of the connective tissue.
“And everyone knows about Marfan because of Lincoln,” says Northrup.
Northrup, 56, herself is no stranger to health setbacks. She has beaten breast cancer three times, the first time when she was just 38, the last time five years ago. Her boyfriend had just proposed to her in February, but the cancer returned in March. “So we had a cancer-shotgun wedding” in April of that year, she says.
“Having had medical challenges myself gave me a little more insight. I can go from personal experience knowing how challenging and frustrating it can be,” she says.
Having your child diagnosed with tuberous sclerosis, Northrup knows, can be hard.
“When parents get the diagnosis, they are devastated,” she says. “Then they get better and they become activists.”
That is MaryJane Mudd’s story. She is a dynamo in getting out the word on the disease, and she has served on the board of the national Tuberous Sclerosis Alliance.
“I’ve met people from all over the world who have enriched my life,” MaryJane says. “I’m not the selfish person I was.”
MaryJane, who works at Shell in external communications in Houston, is an ebullient, vivacious woman who has, as Northrup puts it, “40 best friends.” Northrup, though a little more on the quiet side, radiates a calm, clear optimism. They’re a perfect pair.
The doctor believes the future of the treatment of tuberous sclerosis is bright.
“It’s a wonderful story for genetic disease,” she says.
‘More to the story’
The UTHealth lab, where Northrup has worked with researcher Paul Au for more than 20 years, was the first to propose that there was more than one gene mutation causing the disease. Now they believe there may be a third, or at least another mechanism for causing the disorder, because 15 percent of patients have neither of the known mutations.
“There’s a little more to the story,” Northrup says.
Already, tumors that often compressed the region of the brain known as the foramen of Monro can be controlled with a drug. The same drug has been approved to treat kidney tumors. At UTHealth, they have developed a skin cream using the same drug that can be applied to the face, shrinking the tiny, disfiguring tumors. And it will be inexpensive — maybe only $50 for a month’s worth. (They noticed that patients taking the medicine orally had their appearance improve.)
Great strides have been made, too, in identifying babies with tuberous sclerosis. Early identification can stave off the debilitating seizures, and autism can be treated early. Word is getting out, too: May 15 was Global Awareness Day.
And Mackenzie? She’s doing better, too. Her seizures are controlled, she’s been out of diapers for many years and she can walk and feed herself. firstname.lastname@example.org
Hope Northrup is a specialist in research on tuberous sclerosis, a genetic disease that affects between 1 in 6,000 and 1 in 10,000. Northrup runs a lab at UTHealth to study the disease.
Mayra Beltrán / Houston Chronicle
Chris and MaryJane Mudd are the parents of patient Mackenzie.
Photos courtesy MaryJane Mudd
Mackenzie Mudd was diagnosed with tuberous sclerosis as a 1-year-old. The genetic disease causes benign tumors to grow on vital organs. In the past 20 years, much progress has been made in treatment.