Mosaicism not rare or arcane

National report - Studying the genetic roots of mosaic disorders often presenting in pediatric patients could provide important insights into how effected genes function - and, possibly, direction for future treatments, an expert says.

Although researchers have gradually been unlocking the mysteries of mosaicism over the past 20 years, most dermatologists perceive it as a foreign and esoteric concept, says Jonathan A. Dyer, M.D., assistant professor of dermatology and pediatrics at the University of Missouri-Columbia, Columbia, Mo.

"There's a perception among dermatologists that mosaicism is a rare, arcane concept that doesn't have any bearing on the typical dermatologist," he tells Dermatology Times.

Accordingly, he says that being able to explain the principles of mosaicism to patients and their families is very helpful.

Understanding mosaicism

In explaining many common mosaic skin lesions to patients, Dr. Dyer says, "I often use the term birthmark, because, for many of them, that's what these lesions look like - spots that they've had since birth that will stay with them the rest of their lives."

Most mosaic skin lesions are permanent and incurable by current methods, he explains, because experts believe they're caused by genetic changes in the skin.

More specifically, Dr. Dyer says that mosaicism occurs when an organism is composed of two or more genetically different populations of cells originating from a genetically homogenous zygote.

Just as a mosaic floor can contain pieces of many different colors, he explains, "People, too, can have a similar patterning on their skin, where the skin of the entire individual actually has cells that are genetically different within it."

Depending on where the mutation resides or which genes or proteins are effected, these abnormalities can effect the appearance, growth or function of skin (and other organs), Dr. Dyer adds.

Derms an front line

Because one can see skin changes with the naked eye, he says, "Mosaicism is important to us as dermatologists."

In fact, Dr. Dyer notes that in many respects, "Dermatology has led the way in our understanding of mosaicism as a concept," as dermatologists such as Rudolph Happle, M.D., have striven to understand skin manifestations of this condition.

Many examples of mosaicism frequently used for illustrative purposes are indeed rare and somewhat difficult to grasp, Dr. Dyer allows. Examples include hypohidrotic ectodermal dysplasia, an X chromosome-linked condition whose symptoms include facial and dental abnormalities resulting from mutations in ectodysplasin.

Dr. Dyer says that when it comes to many rare disorders that the typical dermatologist is unlikely to see, researchers know which genetic changes cause them.

"We don't necessarily know exactly why that specific gene change leads to the skin findings that it does," he says, "but we know a bit about what's going on at a molecular level."

Paradoxically, Dr. Dyer says, "Epidermal nevi and pigmentary mosaicism are actually very common, but we know less about causes of those conditions," at least in their most common forms.

For example, he says that with pigmentary mosaicism, which is characterized by strips of hyper- or hypopigmented skin that develop along Blaschko's lines, "Some data suggests that if one looks, one can find chromosomal abnormalities in these areas. But we don't know specifically" what causes these abnormalities.