The Genetics of EB

GENETICS 

The Genetics of EB

This will be my attempt to try and explain the genetic of EB in terms that the average person can understand.

EB is an inherited condition.

Essentially, someone with EB is missing the "glue" that holds the skin together. By doing a biopsy, doctors are able to determine which "glue" a person is missing and therefore tell what type of EB they have.

Recessive forms of EB:

Those include:

All forms of Junctional EB

Recessive Dystrophic EB

Two forms of EB Simplex(EBS-PA and EBS-MD

And a newly discovered form of EB called Kindler Syndrome

In these types, the person with EB received 2 mutations, one from each parent. In recessive EB, it takes 2 copies of the gene that has the mutation on it to make EB. That is why the parents do not have EB, they just have one copy of the gene. But when each of those copies is put together, that makes recessive EB.

With recessive EB, there is a 25% chance with each pregnancy

that the baby will have EB. 

 

 

 

Testing for Recessive EB

In testing for recessive EB, the lab will try and locate the two mutations in the child with EB. After those mutations are found, they will then look in the DNA of the parents to see if they too have the mutations. Once this is complete, you can use this information for prenatal testing in future pregnancies or if you have other children, have them tested to see if they carry one of the mutations so they will know for future reference when they grow up and have kids. Remember that with recessive EB, it takes 2 mutations to make EB, so if your other child(ren) just has one of the mutations, it means they do not have EB, but carry a mutation than can cause EB.

Dominant forms of EB:

Those include:

Dominant Dystrophic EB

Most of the EB Simplex forms.

In these types it only takes 1 EB mutation to make Dominat EB. Typically one of the parents has EB and then passes it on to their child. In this case there is a 50% chance with each pregnancy that the baby will have EB.

Dominant forms of EB can also occur when a spontaneous mutation occurs at conception. No one knows why this occurs, it just does. There is nothing you ate, drank, did, or did not eat, drink or did not do that caused this, it just happened.

Testing for Dominant EB:

In testing for Dominant EB, the lab will look for the mutation in the child. Once that is found, they will compare it to the DNA of the parents.

If they do not find the mutation in either parent, then this was a case of spontaneous mutation.

In the case of spontaneous mutation, the parents of the affected child have a

2-3% chance of having another child with EB. This is due to gonadal mosaicism.

Visual Diagnose of EB

You may have found that many doctor will try to tell you what type of EB your child has just by looking at them. That is usually a very un-reliable way to diagnose a child with EB.

In my experience and observation of babies and children with EB, typically those with recessive forms of EB tend to start out milder in the beginning and get worse as they get older.

And, typically those with dominant forms of EB tend to start out more severe at birth and get better as they get older.

But everyone with EB is different and no two people will present the same way or progress the way the "experts" say they will based on the type of EB they have.

*NEW*

a procedure called PGD-IVF is available to those families wishing to have an EB Free child.  you can learn more about the process here

Biopsy and Genetic Testing:

Biopsy’s can be sent to either of the following places:

Beutner Labs, Inc.

3435 Bailey Ave., East Bldg. 2nd

PO Box 26

Buffalo, NY 14215-0026

716-838-0549

www.beutnerlabs.com

Stanford Dermatopathology Service

Department of Pathology - H2110

Stanford Medical Center

300 Pasteur Drive Stanford, CA 94305 650-723-6736 department of Pathology - H2110

E-mail: dermatopathology@lists.stanford.edu

http://dermatopathology.stanford.edu

Dermatopathology Office,

Gloria Magpantay: 650-723-6736 

 

*biopsy's aren't the "go to" anymore for EB diagnosis.  Genetic testing is much more accurate.

Genetic Testing:

Molecular genetic studies (DNA analysis) is a must more accurate way to diagnosis EB.  Molecular studies are done to identify the specific genetic mutation and to determine the mode of inheritance (recessive vs. dominant)  There is a new genetic test that tests for ALL known EB mutations in one sample: It is called the Epidermolysis Bullosa (EB) XomeDx^®Slice  

 

 
Below are two labs in the US  that can perform genetic test for EB.

1) GeneDx
207 Perry Parkway
Gaithersburg, MD 20877
301-519-2100
www.genedx.com 


2) The Molecular Genetics Laboratory at Cincinnati Children’s  Hospital

EB Statistics

The incidence column is the one that estimates number born in a given year. The last official birthrate numbers are form 2009, and that year it was 4,130,665 (2010 and 2011 are not available)

Material is based on the NEBR study population 

EB type or subtype:	Prevalence*	Incidence**
EB (All types and subtypes, including unclassified patients)	8.22	19.60
EBS	4.60	10.75
EBS, Localized (formerly Weber- Cockayne)	3.14	6.81
EBS, all others	1.46	3.95
JEB	0.44	2.40
JEB-Herlitz	0.07	<0.41
JEB, other	0.37	<2.04
DDEB	0.99	2.86
RDEB	0.92	2.04
RDEB, severe generalized (formerly Hallopeau- Siemens)	0.42	0.41
RDEB, all others	0.49	1.63

*Prevalence of EB patients per one million births (1990)

**Incidence of EB births per one million live births (1986-1990)

Fine, Jo-David and Hintner, Helmut. (2008) "Life with Epidermolysis Bullosa (EB): Etilogy, Diagnosis, Multidisciplinary Care and Therapy" Springer-Verlag/Wien, New York. 

The number in the Incidence Column is per 1 million births so to find the actual number of new cases of EB each year in the US, multiple that number by 4.13 (the approximate total number of births in the US each year)

So there is approximately 80 new cases of EB in the US each year.  Of those 80- 

45 will have some form of EB Simplex

10 will have some form of Junctional

12 will have Dominant Dystrophic EB

10 will have Recessive Dystrophic EB

This is just an approximate # and some years there will be more or less in each category.