Chromosome 15q 11-13 Duplication Syndrome Defined

Chromosomes seen under the microscope look like they have horizontal stripes; these are called “bands”. Each band has a name referring to the location on the chromosomes. This is like an address for a building. It tells you exactly where on the chromosome to look.

The first number in the address is the chromosome number, followed by a p or a q (telling you which arm to look at), followed by number like “11.2” to describe the sub-bands. So, 15q11.2 and 15q13.1 each refers to a specific location, and 15q11.2-13.1 refers to a bigger area (like a street or a city), which includes 15q11.2 and 15q13.1, and everything in between.

People can be missing parts of their chromosomes, and they can also have extra pieces. Missing parts are called “deletions,” and extra parts are usually called “duplications.” Having deletions and duplications can be harmless if they are very small; most of us have these. But, the larger the deletion or duplication, the more likely it will have an effect on the person’s health, growth, or brain development. How the person will be affected depends on the type of genetic information (genes) that is extra or missing.

There are 2 common ways to have extra 15q11.2-13.1 genetic material. In general, the more copies of this region a person has, the more severely affected.

1. Interstitial duplication - this means that the 20 or so genes within the area q11.2-13.1 are present in three copies instead of the usual two.  Another way to say this is “trisomy 15q11.2-13.1.” The usual number of chromosomes is present (46), but on one copy of chromosome 15, there is an extra bit of genetic material.

2. Isodicentric chromosome 15 (usually shortened to “idic15”) – this means that there is an extra chromosome, so that the total number of chromosomes the person has is 47 (instead of the usual 46). But, the extra chromosome is not a full chromosome 15; it is a “supernumerary” (extra) small chromosome that has 2 arms of equal size, and each arm is made up of that extra piece of chromosome 15 (15q11.2-13.1). So, the total number of copies the person has of this important region is four instead of the usual two.

Another way to say this is “tetrasomy 15q11.2-13.1.” Sometimes the isodicentric chromosome 15 is written “inv dup 15,” which stands for “inverted duplication of chromosome 15.” This is because the chromosome looks like a ‘doubled up’ like a mirror image to form an extra little mini-chromosome.

 Less commonly, a person may have an extra chromosome that has only one arm containing 15q11.2-13.1. In this case, the total number of copies of the region is three, so this can also be referred to as “trisomy 15q11.2- 13.1.”  This is not an isodicentric chromosome 15; it may be referred to as “supernumerary marker 15” or “extra structurally abnormal  chromosome (ESAC) 15.”

 It is also possible to have five or six copies of 15q11.2-13.1 material (ie.,pentasomy or hexasomy), but this is quite rare indeed.

  Another form is to have a “mosaic” form of the 15q11.2-13.1 duplication, in which only some of the cells in the body have this extra genetic information, while the rest of the body has the usual amount. People with this form may have no effects at all, or can be as severely affected as an individual with the extra material in all their cells. It is impossible to predict,  because the test that is done to determine mosaicism tests only the blood,  but the brain is where the duplication has the biggest effect, and the degree of mosaicism may not be the same in blood and brain.

Unlike many of the other chromosomes, the 15q11.2-13.1 region is special because some of the genes in this region are “imprinted.”

This means that the body needs one copy to come from mother and one copy to come from father. When a person has a deletion of this region, they will have one of two genetic conditions: either Prader-Willi syndrome (PWS), or Angelman syndrome (AS). If they are missing the father’s copy of 15q11.2-13.1, they will have PWS, and if they are missing the mother’s copy, they will have AS.

If this same region, which is sometimes called the “Prader-Willi/Angelman syndrome critical region” (PWASCR) is duplicated, whether or not the person with the duplication has symptoms depends on whether the duplicated material came from the mother’s chromosome 15 or the father’s chromosome 15. In 99% of cases, people with developmental problems, seizures, et cetera have their mother’s duplicated 15q11.2-13.1 region. Having the same duplication from the father’s chromosome 15 does not seem to cause any problems in general.

What do we know about the genes that live at 15q11.2-13.1?

We know that there are about 20 genes in this region, and experts believe that some of these genes need to be present in exactly 2 copies for normal brain development. Furthermore, some of these genes also need to be present in one copy each from mother and father (the imprinted genes). Experts know more about some of these genes than others. The most important ones seem to be:

  1.  UBE3A – this gene is important for making a protein that acts like a janitor in the brain, cleaning up all the abnormal, damaged or unnecessary proteins hanging around. Only the mother’s copy is active in the brain.
  2. The GABA receptor genes GABRB3, GABRA5, and GABRG3 – GABA is one of the major neurotransmitters in the brain, helping brain cells (neurons) communicate with one another by carrying messages between them.
  3. GABA receptors are the proteins that accept the message, and there are many different types, three of which are made from genes within the 15q11.2-15q13.1 region. Having too many copies of these genes is thought to increase the likelihood of having seizures and possibly autism spectrum disorders.


Regardless of the type of chromosome 15q11.2-13.1 duplication a person has, the same important genetic information is present in extra copies.  It’s sort of like having too much software in your computer.  The messages to the body get confused and we start to see the most common symptoms, all of which are the result of atypical brain development and/or function. These include:

  • Seizures
  • Autism
  • Intellectual Disability
  • Absent/Poor or delayed speech
  • Hypotonia
  • Disordered Sleep
  • Psychiatric problems

This constellation of symptoms is called a “syndrome.” Thus, we refer to individuals with extra copies of 15q11.2-13.1 as having the “Chromosome 15q11.2-13.1 duplication syndrome,” which is a bit of a mouthful! Sometimes this is shortened slight to “15q11-13 duplication syndrome” or “idic15 syndrome”, depending on which is more correct based on the person’s chromosome difference.

As genetic testing becomes more available, clinicians are finding more and more variations in our genetic information.  More frequently we are seeing duplications in other area of Chromosome 15q, like 13.3, 22, 26 etc.  Although there may be some overlap in symptoms, these are considered to be distinct from 15q11-13 duplication syndrome. When accessing medical information, parents, researchers, clinicians and charities need to be sure that they are all referring to the same underlying genetic difference.

Currently there is no curative treatment for Chromosome 15q11-13 Duplication and related syndromes, but there are many supportive treatments, therapies and family resources one can access for help.

Further recommended testing includes:

  • 24 Hr. EEG  with special attention to the background abnormalities
  • SLEEP STUDY due to a high incidence of Apnea
  • MRI
  • ECHO
  • NON-TYPICAL AUTISM SCREENING  

 For more information on accessing Syndrome specific resources and clinicians please contact us.     This email address is being protected from spambots. You need JavaScript enabled to view it.

 

This document was made possible with the collaboration of Dr. Melissa Carter MSc MD
FRCPC Clinical Geneticist Specializing in Autism & Developmental Disabilities
The Hospital for Sick Children Idic15 Clinic, Toronto, Ontario, Canada. 

 

The information provided on the Idic15 Canada web site is designed to support, not replace, the relationship that exists between a patient/site visitor and their medical practitioners.

updated: December 5, 2013