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"Confetti Skin, Beauty Within" is our blog about ichthyosis and its effect on our lives. Rachel and our three boys are affected with the form of ichthyosis called "icthyosis en confetti, type 2".

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Prenatal Screening for Ichthyosis

One often-asked question we hear in various ichthyosis support groups is about prenatal screening for ichthyosis. If these disorders are so severe, why don’t we test for them?

I can think of five separate answers.

1. Compared to other genetic disorders, only a few children are affected with ichthyosis.
2. There are no ethnic risk factors for ichthyosis.
3. Some forms of ichthyosis are the result of spontaneous mutations.
4. There are many different genes that cause ichthyosis.
5. Even severe ichthyosis is largely invisible on ultrasound

1. Compared to other genetic disorders, only a few children are affected with ichthyosis.

A recent study by Dr. Len Milstone determined that roughly 200-400 children a year are born in the United States with a moderate to severe type of ichthyosis. This is about 1 out of every 100,000 births. While this is a higher incidence rate than we used to think of, it’s tiny compared to the genetic disorders that are commonly screened for. For instance, there are 16,000 babies born with phenylketonuria (1 out of every 250 births) and, one out of every 500 African American children are born with sickle cell disease.

The reality of testing four million pregnancies to catch 300 obscure, mostly non-fatal, birth defects is that it costs more than the benefit of screening is worth. (Obviously, it’s worth a lot to affected families, but the health industry is looking at populations, not individuals.)

2. There are no ethnic risk factors for ichthyosis.

If you’re Irish, you might have a higher risk for carrying the gene for phenylketonuria (PKU). If you’re European, you might have a higher risk for carrying the cystic fibrosis gene. If you’re Asian, you might be carrying the gene for thassalemia. If you’re an Ashkenazi Jew, you might carry the Tay-Sachs gene.

But ichthyosis affects everyone. We’re not aware of any ethnic groups who have a higher risk of carrying the gene for a severe type of ichthyosis. With very few exceptions (see “Dozens of cases of ichthyosis in a tiny Mexican town: The Founder Effect in action“), ichthyosis is an equal-opportunity annoyer.

3. Some forms of ichthyosis are the result of spontaneous mutations.

Many forms of ichthyosis are dominant and caused by sudden mutations in a single sperm or egg. As far as anyone knows in those cases, there’s no warning, no rhyme or reason, and no way to prevent it from happening. So if a child’s ichthyosis is the result of one of these mutations, testing the parents wouldn’t have provided you with a lot of information.

4. There are many different genes that cause ichthyosis.

Tay-Sachs and sickle-cell anemia are single-gene mutations. So testing for those mutations is relatively straightforward — there’s only one gene to test for.

But ichthyosis is an entire family of related genetic disorders. A broad test for ichthyosis would mean testing multiple genes. Even if you wanted to test for only a single type of severe ichthyosis, such as ARCI, you’d still be looking at multiple genes.

To make things even more complicated, researchers still haven’t identified the genes that cause some types of ichthyosis. That’s why projects such as Dr. Choate’s Gene Discovery project are so important.

Of course, if you have a specific genetic diagnosis, and want to test for exactly that type of ichthyosis, then that’s a much simpler problem to solve. But that’s really a different issue than genetic testing in the general population.

5. Even severe ichthyosis is largely invisible on ultrasound

Skin on a baby in the womb doesn’t develop into mature layers until late into pregnancy. This article says that the process begins around 22-24 weeks and doesn’t complete until right before birth. Skin starts to look mature around 30 weeks, but even then, it’s hard to notice anything via an ultrasound because the baby is in amniotic fluid and it takes time for the layers to build up.

Harlequin ichthyosis, the most severe form of autosomal recessive congenital ichthyosis (ARCI),  has been identified several times since 1980 via ultrasound. Since there are so few babies born with harlequin ichthyosis each year, we think it’s usually pure luck that cases are caught. Both Courtney and Alicia said that they had no warning, but Evan’s was identified via ultrasound at 27 weeks, but his mom said that she was at the doctor for unrelated reasons.

In 2010, doctors from Poland and Belgium wrote about a case in the Journal of Ultrasound in Medicine, “Prenatal Diagnosis of Harlequin Ichthyosis Using 3- and 4-Dimensional Sonography“, JUM February 1, 2010 vol. 29 no. 2 317-319 (PubMed link). In addition to several other abnormalities, the doctors observed ectropion and eclabion. They diagnosed harlequin ichthyosis combined with “some prominent overlapping Neu-Laxova syndrome (NLS)”. The baby was stillborn. Pictures from the ultrasound and of the stillborn baby are at the bottom of the article; they are at least as graphic as some of the photos which have caused distress, elsewhere.

Our own family has a much less severe form of ichthyosis than harlequin ichthyosis, and we weren’t successful in our own attempts to use 3- and 4D ultrasound to figure out what we were in for. With ultrasounds at 30, 33 and 35 weeks for Monkey, and at 35 weeks for Momo, and specifically looking for ichthyosis markers, our experts found nothing conclusive. Yet days later, they were born affected.

So in conclusion, we think that prenatal testing is most likely to be worthwhile when one parent or an extended family member has a recessive type of ichthyosis. And testing in that situation will be much simpler if the affected individual had a specific genetic diagnosis. Without knowing the specific gene involved, there would have to be a lot of speculation.

4 comments to Prenatal Screening for Ichthyosis

  • Cindie Hamilton

    Wonderfully written. I’ve got EHK so we are able to do an amnio anytime I have kids (currently have 2, 1 affected). There are several friends who had children that were born with spontaneous mutations of Ich.

  • Me

    Hello! I really respect you doing this information. I´m 29 years old finnish woman and have erythrokeratoderma variabilis and my dad has it too. I have been wondering many years how could I stop the disease, I mean how won´t it pass to my children.

    You wrote: “So in conclusion, we think that prenatal testing is most likely to be worthwhile when one parent or an extended family member has a recessive type of ichthyosis.”

    Why only resessive? How about dominant? My and my dad´s EKV is dominant and the risk is bigger (50 %) to pass it to my children. Do you know is there any way to prevent it? Or do you know what does mean “with nearly complete penetrance”? Does it mean the risk is actually more than 50 %..???

    Thank you before hand! -Susanna

    P.S. I know I would love my children with or without EKV, but we have other risks too (my man has epilepsy and atopy), and I really won´t like our children to be bullied. My and my dad´s desease is really hard to care about too (creaming, cleaning the skin, the clothes and house, bathing etc.. you know…)

  • Rachel See

    Hyvää huomenta, Susanna. With a genetic diagnosis (i.e., a known mutation), it is possible to do IVF and then test the embryos for the mutation, and then choose to implant only the embryos without the mutation. This adds costs to the (already-expensive) IVF process — although I’m not sure what Finnish health care pays for!

    Prenatal testing for you isn’t helpful, since it’s pretty clear whether you either have it or not. And if you have it, there’s a 50% chance of passing it on to a child.

    I’ll make sure Jennifer sees this so she can follow up, too.

    Comments on these older threads tend not to get as much attention, so feel free to follow up with us via email or on Facebook.

  • Jennifer See

    Hyvää huomenta, Susanna! You are correct that in your situation, with a known dominant gene that you carry, you could very well test to see if an embryo is affected by EKV. The article was written by me and I guess I wasn’t as clear as I should have been. It was aimed at answering the question of why we don’t test all unaffected parents for ichthyosis as a general rule, and not really aimed at people that already have the dominant mutation and are looking to not pass it on (which is our situation, as well).

    For you, since you know your mutation, as Rachel suggested, you could undergo IVF/PGD, which is a process where they harvest and fertilize the eggs in the usual IVF manner, then at 2 days, remove one cell from the embryo and test it for ichthyosis. If it is unaffected, it can be implanted, and if affected, discarded.

    A second way to avoid passing it along would be to get pregnant and have an early amniocentesis done, where the cells are tested in the fluid. At that point, if you had an affected fetus, you would have to make the choice to carry or abort.

    Both of these methods have sticky ethical issues that you have to decide if you are comfortable with.

    Kiitos käsittelyssä blogistamme!

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