You're not likely to find "restricted dermopathy" in the medical dictionary. It's too unusual a disorder.
"It is extremely rare," concurred cell biologist Jeffrey Miner, at Washington University in St. Louis. "There are only about 40 cases in the literature. It does appear to be genetic but very sporadic. The 40 newborns," he added, "died within the first week of life. The reason is thought to be primarily their inability to breathe properly. That's why it's called restrictive dermopathy [RD], because the skin seems to be so tight that the child cannot expand its chest to bring air into the lungs.
"How long a human RD infant can stay alive after birth varies between hours and a few days," Miner continued, "depending on medical care. With today's pediatric and neonatal facilities, the child is likely to get to live just a little bit longer than in the past.
"No twins have been born," he noted, "but a pair of parents has given birth to more than one set of siblings. The mother and father probably carried a single mutation in the RD gene, but it takes two copies of that mutation to really cause the disease. The fact that it's so rare means that there aren't a lot of people walking around with a single RD gene mutation."
Miner is senior author of a paper in the Proceedings of the National Academy of Sciences (PNAS), released online April 8, 2003. Its title: "Positional cloning of wrinkle-free, a previously uncharacterized mouse mutation, reveals crucial roles for fatty acid transport protein 4 in skin and hair development." However disparate they seem, wrinkling and obesity both derive from the same protein encoded by the restrictive dermopathy gene. That protein is FATP4 - the fatty acid transport protein 4.
"Our finding in this paper," Miner told BioWorld Today, "is the important connection between a protein that is thought to be involved in obesity and a role for it in mouse skin and hair development, as well as skin tightness and wrinkling. Presumably," he added, "both may be influenced by the same gene that encodes FATP. It will apply to human hair and wrinkling, too. Of course we don't know anything about that yet," Miner allowed, "but in most cases genes that have a role in the mouse also have a very similar if not identical role in humans."
Researchers See Obesity Fix In Protein Inhibitor
"What's novel in this paper," Miner continued, "goes back to no one having envisioned a role for this particular protein in the skin or in the hair. We knew when we discovered it that companies were interested in finding an inhibitor for FATP4 to try to prevent obesity. So there's no reason to think that if an inhibitor is found it could also be used in certain areas of the skin, perhaps on the face, to prevent wrinkling and hair growth.
"And in fact if this drug were to be used for obesity there might be side effects that affect the skin and the hair, so it's important to know that as well. I think total hair loss would be quite negative, but skin tightening might not be viewed as harmful. Now that this PNAS paper is published, I shall be in contact with companies that might be interested in the wrinkling aspect.
"That aspect is of some concern to maternal cats, dogs and mice," Miner explained. "Puppies and kittens have very loose skin so their mothers can pick them up by gently biting their necks. Mice, too, pick up their offspring the same way, so the neck is one place that has quite a bit of baggy skin. Normal mice are born with wrinkled skin. That begins a few days before birth. As these mice age after birth, they grow a full body of fur and nobody thinks about their having wrinkled skin or not.
"Nude mice, which lack hair, are quite wrinkly. However, the mutant mice, we found, do not have those wrinkles. Even from the very beginning of the wrinkling stage of development, there's a defect in these mice. So even if these RD mice could breathe normally, we think they would still die because their barrier would not be intact, so they could not retain moisture, and would be subject to environmental damage."
Skin's Job: Keep Water In, Garbage Out
"One of the major purposes of the skin of animals that live on land is to prevent evaporation of water from within the body and to prevent the entry of harmful substances from the outer environment. So the skin is very specialized. Its epidermal part is composed of a layer of four different cell types, and we think that FATP4 plays some role in either the differentiation or morphology of these cells. In its absence, they are not able to properly form the barrier.
"We were very interested to find out how this mutation affected hair growth," Miner recounted. "The fact that mice are born without any hair, and these mutant mice die shortly after birth, prevented us from seeing how hair from these RD mice regrow. So we took skin from one such mouse and grafted it onto a nude mouse, which has no immune system, so the hair or skin graft wouldn't be rejected. We let the grafts develop for between one and eight weeks and then found that there was a severe impairment of hair growth from the wrinkle-free mutants. Our conclusion was that this protein does have an extremely important role in hair growth, though we don't yet know what that role is. That," Miner commented, "will take an additional experiment.
"The university," he observed, "has filed a patent application, claiming the use of inhibitors to FATP4 to prevent or reverse skin wrinkling and hair growth. I and my first PNAS author, Casey Moulson, are the two inventors. Millennium Pharmaceuticals," Miner noted, "already has a patent on this protein but at the time it was patented there was no idea that it could be involved in the skin. It was really finding inhibitors for preventing obesity. My hope," Miner concluded, "is that if they find an inhibitor our patent will cover its use on the skin."