Last week, we learned about several news articles about icthyosis in a tiny, rural mountain village in Mexico, Soledad Atzompa. There are an astounding number of affected people in a very small region. There are also several other articles regarding the situacion and all have similar information. There is more coverage about the town of Nogales,about 20 minutes away. (All links are to Spanish news. There doesn’t seem to be any English coverage. Use Google Translate to translate the pages.)
There isn’t a whole lot of specific information in the articles, which mostly talks about area advocates demanding that the region’s health service send out doctors to care for all these affected people. The articles blame “paperwork snafus” for not getting the requested aid in, say that the doctors left after doing initial screenings, and that they are now offering low-dose Neotigason as a treatment. One particularly astounding article discussed the comments of a local health official, Ricardo Muñoz Cortés, who blamed the parents for not using contraceptives. Senor Muñoz Cortés, surely a candidate for humanitarian of the year, said that people in the town wouldn’t have this problem if they stopped having babies if a family member was affected or they already had an affected child.
The people interviewed say that they don’t really understand why their children are affected or why this is such a problem in recent history. Also, they are not entirely sure if the cause is genetic, an illness, or something in the environment that is causing the problem.
I did a bit more searching and found that Soledad Atzompa is a small, isolated mountain town of around 650 inhabitants. Nogales is the equivalent of the county seat, about 7 miles away, and hosts most of the population of about 30,000 in the entire county. 1/4 have never been to school and another 1/3 never completed school. 18,000 of them are indigenous, and 10,000 are children. Nearly all of them speak a local language, although slightly more than half speak Spanish as well.
(Contemplate that for a minute. Here we have an uneducated, impoverished community which for religious or other reasons doesn’t use birth control, and yet the health officials want to treat the affected people with Neotigason, which is known to cause severe birth defects. Wow.)
The first article we found said that more than 60% of the population of that town is affected by ichthyosis. On first glance, this seems absurdly high, and we wonder if it’s a mistake or miscommunication. If a town of 650 people had 60% of its population affected with ichthyosis, that would be 390 affected people. Other media coverage about Soledad Aztompa talks about “37 people” (as of July) in the town having ichthyosis. This article says that there are over 100 cases in the 2 towns. Those are huge numbers, but they’re nowhere near 60%. More like 16%. Rachel thinks that it’s just the reporter confusing “being affected” by icthyosis with simply “carrying the gene” that causes ichthyosis. I think it’s more likely that 60% of families have an affected family member. At any rate, it’s unclear from what is available.
Pictures from the news articles pretty clearly show the lamellar form of ARCI. These pictures look almost exactly like many of our friends who have ARCI. At events like the FIRST family conference, there might be few dozen or so people with the exact same type of ichthyosis (who travel from all around the United States or even from around the world) to get together and share stories and advice. For those of you who have attended the FIRST family conference, imagine the ARCI breakout session, and then imagine if all of the people in that room came from the exact same small town. That’s what’s happening in Soledad Aztompa.
But we know from our basic genetics and incidence studies that all forms of ARCI are incredibly rare, and that includes the type shown in the pictures of the affected people from Nogales and Soledad Aztompa. So how could a small village have so many affected children?
My first instinct is that the small, isolated community has been subjected to a founder effect. A founder effect is when an isolated population in a fairly small community can trace their ancestry back to a single or just a few individuals. A founder effect isn’t saying that people are committing incest or acting beyond social norms. Rather, it reflects the reality that in small, isolated communities, everyone is often distantly related — like a third, fourth or fifth-degree cousin.
In this scenario, if a common ancestor carried or developed a recessive mutation (such as the mutation which causes ARCI), roughly half of his children would inherit the gene which causes ARCI. None of those children would express the gene, though — in other words, they wouldn’t have any symptoms of ichthyosis — because with a recessive gene you need 2 copies for the trait to appear. Using averages, one fourth of the common ancestor’s grandchildren would also wind up inheriting the recessive gene.
In most cultures, first cousins generally don’t marry, but second cousins (your cousin’s cousins) and beyond (your cousin’s cousins’ cousins!) often wouldn’t even know they are related. In small populations, it is also entirely likely that most of the town is distantly related and therefore has a higher than typical chance of carrying a recessive mutation. The further down the generations you go, the more affected people you see.
In the above (completely hypothetical) example, either person I1 or I2 had a recessive mutation. Generation II had a 50% chance of getting that mutation, and in this case it looks like all 3 kids got it. They all married unrelated people, so none of Generation III got 2 copies of the mutation and all had the normal trait, just like parents and grandparents. In this example, all of the Generation III people inherited the mutation, too (although in reality you’d be looking at 25%. Maybe this graphic left off all the unaffected kids.)
At Generation IV, things get interesting. First-cousins III7 and III8 married. Clearly both parents are carriers for the mutation because 2 of their kids have the recessive trait. Surprise! It seemingly appeared out of nowhere.
In Generation IV, there are cousins and second cousins intermarrying, too, and their children (Generation V) also have about a 25% chance of being born with the mutation.
Here’s a real-life family tree of a different disorder coming from a founder effect. In this case, the ones with only 1 square colored in would be the unaffected carriers, the white circles and squares don’t have the mutation, and the ones that are blue are affected people. At the top, you’ll notice that none of the generations had the disorder. At the bottom, it was pretty common in the population.
As you can see from all the black squares, the gene got carried down the line for 11 generations, but it only became expressed twice in generation 10, 4 times in generation 11, and had the tree continued, the next generations would see more and more affected children as the recessive trait becomes more common in the population.
Remember, recessive does not mean “bad” or “rare.” It just means something else covers it up. Type O blood is recessive, yet it is the most common blood type.
Numerically, this is how it works out:
Chance that you’re a carrier x chance that you pass on the carried gene x spouse chance of carrier x spouse chance of passing on the gene.
In a normal population with members adding and subtracting to the population (and therefore not marrying distant relatives), odds are 1/250 x 1/2 x 1/250 x 1/2 = 1/250,000 affected by ARCI.
In a founder-effect population, odds vary by the generation, but because everyone came from the same ancestor, every 8th or 16th person might be carriers. So… 1/8 x 1/2 x 1/8 x 1/2 = 1/256.
As the generations go on, this unseen gene gets picked up by more and more people. They have no idea that they carry it, as all the ancestors are unaffected. At some point, it is possible that most people have it. Then you get to a point where your odds are 1/2 x 1/2 x 1/2 x 1/2 = 1/16. I believe that’s what we are seeing in this little town in Mexico. So even if there wasn’t historically any incidence of severe ichthyosis in this area of Mexico, basic genetics can show us how it might appear “out of nowhere” in recent years.
We hope that appropriate treatment and counseling can make its way down to Nogales. The area is impoverished and faces so many other issues, though. It’s unreasonable for us, blogging here in the comfort of our home, to think that genetic screening and counseling is feasible for this population. But for more fortunate people with a history of ichthyosis in their family, genetic screening is possible and can be very helpful in allowing parents to make fully informed decisions about the chances that their future children might have a severe form of ichthyosis.
(There will be a whole series of genetics posts coming up soon. I just have to finish writing them! We wanted to publish this one now because it is in the news.)
EDITED 10/19 @ 12:00 PM: Edited to clarify “60%” comments and geography. Links also edited/fixed.