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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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Here's our summary of our best and most important posts of 2012.

Genetics Part 5: Dominant Inheritance

The most common and some of the very rare types of ichthyosis are inherited in a dominant fashion. This means that only one copy of the gene is needed for the disorder to appear. There are 2 ways to inherit this sort of disorder: either your parent is affected and you drew the short straw on a 50/50 chance, or it appeared out of nowhere from 2 unaffected parents that happened to meet a sperm and egg where a random mutation just happened to be in a particular skin-making gene.

As with recessive disorders, having a dominant gene does not mean that it is good or bad, it just means that you only need one copy for the gene to express itself in you. While many dominant genes are vital to your existence, others have little impact (brown eyes, widow’s peak hair), and still others cause body disorders and diseases that can be incompatible with life, present at birth (ichthyosis), or cause problems only later in life (such as Huntington’s Disease).

The most common question I have answered, ever, is “How did this happen to me? It has never been in my family before.

Imagine that we have a random gene, A. A is the dominant copy of the gene, and it will be expressed as long as at least one copy is in a child. Aa results in the dominant trait. Lowercase a is the recessive gene, and for it to appear, a person must have 2 copies, aa.

We set up a box, called a Punnett square, with the father on the top and the mother on the side. Let’s assume that we have a parent with normal skin and a parent with epidermolytic ichthyosis (formerly known as epidermolytic hyperkeratosis, or EHK). Then we fill in the box with the letter from the matching top and side, and inside the box gives you all possible combinations in the children.

A a
a Aa aa
a Aa aa

As you can see, two boxes have Aa, which means that they will be affected by epidermolytic ichthyosis because they have A, and two will be unaffected because they have aa. Whether they are boys or girls has no impact on being affected or not. In this case, with an affected parent, 1/2 of that parent’s sperm or eggs carry the mutation, so each child has a 50% chance of being affected.Autosomal_dominant_-_en.svg

Now, imagine that you are two unaffected parents. A baby is born with epidermolytic ichthyosis. Where did it come from? The answer is that in the course of making that particular sperm or egg, the gene that cause epidermolytic ichthyosis got messed up. But just in that sperm or egg. The Punnett square box looks exactly the same as the affected adult example above for that child, and in fact, for all of that child’s affected children. For any unaffected child, the box looks like the one below, the same as the unaffected parents.

But the next time those same unaffected parents go to have another child, the only gene they can pass on is a. Why? Because there’s nothing in the sperm or eggs that caused that particular mutation. The next child might be a surprise redhead or have blue eyes or all sorts of other random traits, but the chances that another child would have the same ichthyosis mutation are on par with winning the national lotto twice.

a a
a aa aa
a aa aa

This box shows all parents and all children inheriting the normal skin recessive mutation.

Many forms of ichthyosis are dominant. Here are the main ones.

Ichthyosis vulgaris is the most common form of ichthyosis, affecting about 1 in every 250 people. Recent research suggests that this type is actually a co-dominant disorder, which means it has a dose effect. That is, if you have 2 copies of the mutation, your symptoms are more severe than if you have one copy. (The British Journal of Dermatology. 2007;157(3):441-449.)

Darier Disease is much rarer, and affects about 1 in 55,000 in the US. (higher in Scotland and England, lower in Denmark)

Epidermolytic ichthyosis, affects 1 in 300,000. Roughly half are new mutations. The other half are from an affected parent having affected children

Ichthyosis-en-confetti, unknown incidence.

Erythrokeratoderma Variablis – extremely rare. Orphanet suggests 1/1 million, but the actual number is uncertain.

KID syndrome – extremely rare. Orphanet suggests 1/1 million.

The table for dominant disorders is a lot shorter than recessive disorders because there is no carrier. You are either affected, or you’re not. With the exception of ichthyosis vulgaris, it is extremely unlikely that anyone would have two copies of a dominant ichthyosis mutation.

Parents Parent 1 chances Odds Parent 1 passes mutant Parent 2 chances
Odds Parent 2 passes gene Multiply for total odds
2 random unaffected people plan children  1/150,000 1/2 Normal 1/1 1/1 1/300,000 Here, you’re one of those 100 parents that get a surprise at birth
Surprise affected baby, planning more kids* 1/150,000 1/2 Normal 1/1 1/1 1/300,000 Each child has the same chance of a spontaneous mutation, unrelated to what a previous child had.
Affected person, partner is unaffected 1/2 1/1 Normal 1/1 1/1 1/2 50% chance of having an affected child with each pregnancy.
Both parents spontaneously mutate the same gene at the same time 1/150,000 1/2 1/150,000 1/2 1/90 billion Impossible. There are only 7 billion people on the planet.

*It’s possible to be affected with a mosaic mutation, in which case you could have multiple affected children from unaffected adults. It is pretty rare, but not impossible. It is also possible that Parent 2 could develop a mutation in the same gene, but the odds don’t change in that sort of situation. 2 new mutations in the same family is extremely unlikely, as the last box shows.

This is a series of posts on genetics. More information is available in the following links:
Genetics 1: What’s a Gene?
Genetics 2: Recessive Inheritance
Genetics 3: X-Linked Inheritance (X-linked Ichthyosis)

Genetics 4: X-Linked Inheritance (CHILD Syndrome)
Genetics 5: Dominant Inheritance <–You Are Here
Genetics 6: Mosaicism
Genetics 7: Video explanation of how mutations work
Genetics 8: Why we don’t do automatic prenatal screening for ichthyosis

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