Quebec/Newfoundland Families Suffer Rare Defective Gene

When Maryse Robillard was growing up in rural Quebec, she had no idea she carried a defective gene for a horrible disease. She continues to feel fine, as does her husband, whose DNA carries a similar mutation. Then the Robillards had Roxanne, who wasn't as lucky.

Quebec/Newfoundland Families Suffer Rare Defective Gene

When Maryse Robillard was growing up in rural Quebec, she had no idea she carried a defective gene for a horrible disease. She continues to feel fine, as does her husband, whose DNA carries a similar mutation. Then the Robillards had Roxanne, who wasn't as lucky. With a defective gene from each parent, the girl developed one of several nerve-damaging diseases collectively known as hereditary sensory and autonomic neuropathies, or HSANs; as a result, Roxanne does not feel pain in her extremities, especially her lower legs. At first blush, that may sound like a good thing, but it isn't. Far from it. One night, the little girl, who was four at the time, tumbled out of bed. Her parents noticed that her foot was swollen, and thought she had somehow knocked it in the fall, but an X-ray revealed she had broken a bone some indeterminate time ago. In any other child, says Robillard, 34, the break and the ensuing damage caused by ignoring the injury would have caused an inordinate amount of pain. "But she'd been walking, running, and jumping just like the other kids."

Roxanne, who is 10 now, has HSAN type 2, or HSAN2. Exact numbers of people affected by it are hard to come by. It remains rare in Quebec, but not in Lanaudière, a region north of Montreal that includes Terrebonne, Rawdon and Joliette. Dr. Bernard Brais, a neurogeneticist at the University of Montreal, estimates that between one and three per cent of the Lanaudière population carries a copy of the defective gene, which was likely introduced with the first French settlers. Today, 80 per cent of HSAN2 cases studied by Brais and his team - they are tracking two dozen - come from the region. One tiny village has been struck particularly hard - the one where the Robillards live - but Brais declines to name it, not wanting to stigmatize the inhabitants. Patients have a rough enough time of it as it is. They bump themselves without feeling it, the injuries become infected, and infections can spread to the bone, which often leads to amputations. "Many of our older patients," Brais says, "have no feet and no fingers left."

HSAN2 was first described in the scientific literature in 1973. To date, 50 per cent of the patients discussed in journals are of French Canadian descent. (Newfoundlanders also suffer from HSAN2. It is thought that the damaged gene was introduced there by a family from Dorset, in the United Kingdom, in the early 1800s.) Symptoms usually first appear during infancy or early childhood, and generally affect regions below the elbows and knees, in a so-called sock-and-glove pattern. "The degree of insensitivity is quite dramatic," Brais says. "Some of these patients are amputated without anaesthesia - you can cut their bone and they just don't feel anything."

Within the past decade, researchers have sequenced the mutated genes responsible for HSAN2 and four other varieties of HSAN. HSAN3, for instance, is like HSAN2 in that the implicated gene is recessive, meaning two defective copies have to be inherited - one from each parent - to fall ill. (If a carrier has a child with another carrier - as in the Robillards' case - the couple has a one-in-four chance of having a child with the disease.) HSAN3, closely associated with Ashkenazi Jews, is more complex, however, and includes mental retardation and major problems controlling blood pressure.

Anecdotal evidence suggests carriers of a single copy of the mutated gene may be slightly less perceptive of pain, cold in particular. "A lot of the parents of these children are fine," says Brais, "but these are the people who go outside at -30 and shovel with a thin sweater, no gloves and running shoes." This apparent resilience to frigid temperatures may have factored in early French settlers remaining in a region with bitterly cold winters. Other studies may lead to a better understanding of pain and pain management.

In her brief life, Roxanne Robillard has had to endure several fractures. In one case, a cast put on to repair a broken heel bruised her enough to break the skin, cause an infection and eventually an open sore through which her mother could see the child's bone. Today, the girl is confined to a wheelchair, this time recovering from a broken thigh bone. That, coupled with widespread ignorance of the disease, can frustrate Maryse Robillard. "When we tell people she doesn't feel anything, they sometimes say, 'Hey, that's great if it doesn't hurt,' " Robillard says. "And I tell them, 'Yeah, well, she wouldn't have been hospitalized all those times had it hurt in the first place.'" She'd likely be the first to tell you, no pain really is no gain.

See also GENETIC DISEASES.

Maclean's January 30, 2006