BOSTON (Boston Globe) - A disease as rare as it is disfiguring - it distorted the face of the youth in the 1985 movie ``Mask'' starring Cher - has been traced to its genetic roots by researchers at Boston's Forsyth Institute and the Harvard School of Dental Medicine.

About 100 people in the world are known to have craniometaphyseal dystosis, or CMD. It causes bones of the skull and face to thicken progressively, beginning early in childhood, sometimes to twice their normal thickness. Minerals are deposited in the bone so abnormally that the bone becomes as hard as ivory in some patients.

The face grows misshapen: a bulging forehead, eyes widely spread over a broad nasal bridge and a protruding lower jaw. Overgrowth of bone may squeeze crucial nerves for vision and hearing, and can even fatally compress the spinal cord in the neck. In the movie, which Cher has said is the most meaningful of all her films, her teen-aged son Rocky overcomes the birth defect socially but dies in the end.

Researchers led by Ernst Reichenberger and Dr. Bjorn R. Olsen of the Harvard-Forsyth Department of Oral Biology are reporting the gene find on the Web site of the American Journal of Human Genetics.

The discovery is ``incredibly exciting,'' because it holds the promise of eventually developing treatments or even averting the development of CMD, said Dr. John Mulliken, director of craniofacial surgery at Children's Hospital, where some CMD patients have been treated. A foundation established by Mulliken provided some of the funding for the gene research.

Reichenberger said it took about five years to find the gene, which lies on Chromosome 5 and, when mutant, causes the abnormal hardening and thickening of the skull bones. The mutant gene makes an abnormal version of a protein called ANK, that transports minerals from the inside of cells to the outside. The wrong version of ANK can cause minerals to be deposited too densely in bone as it forms, Reichenberger said.

Normally, bone continuously forms and then degrades in a cycle that renews the human skeleton every 7 to 10 years, said Reichenberger. In CMD, new bone is deposited on top of old bone which doesn't get eliminated by cells called osteoclasts that normally degrade it.

Gene sequences from the public Human Genome Project and the private company, Celera Inc., helped the scientists zero in on the gene.

At present, the only treatment for CMD is to remove excess bone and try to keep the thickening from damaging nerves. The operation involves removing the skull bones, paring them down with power tools, and replacing them.

The excess bone growth continues for years, so the surgery may need to be repeated a number of times.

Dr. Jeffrey Fearon of the North Texas Hospital for Children, said he has operated on two children with CMD in the past 15 years. Their skull bones, he said, ``are very, very dense and it makes it hard to correct them.''

Reichenberger cautioned that translating the discovery into improved treatments will take much time. ``It's an illusion to think that there's a big fix out there right now,'' he said. ``We hope our contribution will be to understand better'' the processes by which bones form, how they maintain their shape, and why bones sometimes become too hard - a disease called osteopetrosis - or too weak, as in osteoporosis.

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