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7q11.23 duplication syndrome

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Condition

We hope that you find the information on this condition useful. Please keep in mind that genetic conditions are quite variable, and rarely affect two people in the exact same way.

What is 7q11.23 duplication syndrome?VIEW DETAILSHIDE DETAILS

7q11.23 duplication syndrome is caused by having additional genomic information at chromosome location 7q11.23. This condition may be called the "reciprocal condition" to Williams syndrome (Williams syndrome is caused by having a loss of genomic information at chromosome location 7q11.23).

There is no cure for this condition, but having a diagnosis can help guide a person’s health care, provide information regarding recurrence risk and lead to targeted testing for at-risk family members.

Features

Given that relatively few people with a 7q11.23 duplication have been reported, it is difficult to provide detailed information on the clinical findings associated with this duplication. This page will focus on some of the findings that have been reported in multiple people, though this condition is associated with variable expressivity. This means that features may vary from person to person (even those in the same family).

People with a 7q11.23 duplication are reported to have speech delay, autism spectrum disorder, and anywhere from normal intellect to moderate intellectual disability. They may have medical features including low muscle tone (hypotonia), birth defects such as heart defects, and seizures. They may also have subtle, unique facial features.   

Statistics

The 7q11.23 duplication syndrome has only recently been characterized; therefore it is difficult to pinpoint just how often it occurs. It is thought that this occurs in around 1 in 13,000 to 1 in 20,000 individuals. Because there is a wide range of features and some people with milder features may not be recognized, it may be underdiagnosed. Most duplication syndromes affect males and females of all ethnic backgrounds.

How did this happen?VIEW DETAILSHIDE DETAILS

It may help to first review some background information. In general, the cells of our bodies each have 46 chromosomes that come in 23 pairs. One of each pair is from the mother through the egg cell, and the other is from the father through the sperm cell. The first 22 pairs are the same in males and females. The last pair is the sex chromosomes, which differ in males and females. Females have two X chromosomes (written as 46,XX) and males have one X and one Y chromosome (written as 46,XY).

The chromosomes are divided into two arms: a “p” or a “short” arm and a “q” or a “long” arm. These arms are separated by a center, called the centromere. When scientists look at chromosomes under a microscope, they can see the p arm, q arm, and centromere. Also, special stains are added to the chromosomes to make them appear to have black and white stripes. These black and white stripes are called bands and are given numbers to indicate how far from the center they are located. Chromosomes are made up of DNA, and the DNA of each chromosome has many genes. Genes encode proteins, which perform specific functions related to growth and development (because chromosomes come in pairs, there are typically two copies of each gene).

The cause of 7q11.23 duplication syndrome is a gain of multiple genes on one copy of chromosome 7. This duplication is thought to be the result of nonallelic homologous recombination or NAHR. 

NAHR is a biologic process that makes certain parts of our DNA prone to duplications and deletions. NAHR occurs when regions of the chromosome that have similar sections of DNA are misaligned. When the chromosomes are copied the result is one chromosome with a duplication and the other with a deletion. When this occurs in reproductive cells (sperm or egg cells), a baby can have a syndrome associated with either the duplication or deletion. The syndrome caused by the duplication and the one caused by the deletion are called reciprocal conditions. While they involve the same area on the chromosome, they are distinct conditions and present with different features. It is important to note that a person only has one of the reciprocal conditions—in this case 7q11.23 duplication syndrome (rather than 7q11.23 deletion syndrome, also known as Williams syndrome).

 

Can this happen again?VIEW DETAILSHIDE DETAILS

When a duplication is identified in a person, most people wonder what the chance is for another family member to have the same deletion and the same or similar clinical features (recurrence risk).

There are several factors to consider when discussing recurrence risk with your medical providers. The first consideration is whether a duplication is de novo (new) or inherited from a parent.

  • If the duplication is de novo, there is less than a 1% chance for any other family members have the duplication.
  • If the duplication is inherited from a parent, there is a 1-in-2 (or 50%) chance for additional family members (brothers and sisters of the person with the duplication) to also have the duplication.
  • Of note, whether a person's duplication is de novo or inherited, there is a 1-in-2 (or 50%) chance for each of his or her children to have the duplication.

If a duplication is inherited (is found in the DNA of a parent), that parent is expected to have some clinical features of 7q11.23 duplication syndrome. However, since 7q11.23 duplications are associated with variable expressivity, that parent could have different features from his or her child, and they may be subtle.  

The presence of this 7q11.23 duplication, whether de novo or inherited, is not caused by anything parents did before or during the pregnancy.

Who else should be tested?VIEW DETAILSHIDE DETAILS

When a person is diagnosed with a 7q11.23 duplication, families find it helpful to speak to a medical geneticist or genetic counselor. These specialists can discuss targeted genetic testing, called fluorescence in situ hybridization (FISH) analysis, which can be performed on at-risk family members.

What can I expect?VIEW DETAILSHIDE DETAILS

For this specific duplication, it is important to keep in mind that the condition has only been recently characterized and more information is likely to become available in the future. The following sections are based upon the published medical features of people who have been diagnosed with this condition. A person with this diagnosis may not have difficulty with all of these features or may have additional problems not listed below.

During pregnancy

In many cases, there may be no signs or features during pregnancy that indicate a developing baby has a 7q11.23 duplication. However, there have been reports of birth defects such as heart defects, brain malformations, a defect of the diaphragm (called a diaphragmatic hernia), and a cleft in the roof of the mouth (cleft palate). These birth defects could possibly be seen on ultrasound during the pregnancy. However, if one or more of these features is present, they do not always mean that a baby has this condition. This is because there are many causes for these features. 

If there is a family history of this duplication, parents may consider prenatal diagnosis. With this testing it is possible to know if a developing baby has the duplication; however, it is not possible to know if there will be features or how severe the features will be. Remember, the features associated with 7q11.23 duplication syndrome can vary from person to person, and even from family member to family member. The risks and benefits of prenatal diagnosis are different for every family. If you are interested in prenatal diagnosis you should speak with a genetic counselor.

As a newborn and infant

There may not be any physical features during infancy that suggest the presence of a 7q11.23 duplication. However, a person with this duplication might have subtle, unique facial features. These may be difficult for someone other than a medical geneticist to recognize and may include straight eyebrows, a broad nose, thin lips, and a short philtrum (the area between the nose and lips). These features do not generally cause medical problems but may lead medical providers and parents to suspect that the infant has an underlying medical condition.

Developmental delay is a frequent finding in people with a 7q11.23 duplication. These could be delays in motor milestones (such as rolling over, crawling, or walking), speech development (such as babbling and saying words), or social interactions (such as smiling and making eye contact). Some infants with this condition have low muscle tone (hypotonia).

Seizures are another common feature. There are many types of seizures. They may be subtle or obvious and may respond well to medication. If there are concerns for seizures in a person with 7q11.23 duplication syndrome, a neurologist can help evaluate and manage a treatment plan.

During childhood years

Much like other children, those with 7q11.23 duplication syndrome will have common illnesses and injuries. Some medical problems that are more common in children with this finding are birth defects (as previously mentioned). Also, seizures may continue to be a medical problem through childhood. Some people have flexible joints (hypermobility) and males may have undescended testes (cryptorchidism) that may require surgery.

Speech delay and language impairment have been reported in almost all people who have this duplication. Additionally, a diagnosis of autism spectrum disorder is common.

A child with a 7q11.23 duplication who has developmental delay or intellectual disability may require extra attention in the school setting. For this reason, as well as the risk for autism spectrum disorder, a child could have a neurodevelopmental assessment through a developmental pediatrician or through the school system. A developmental pediatrician or the school system should provide assessments that will help to create an individualized education program or IEP. IEPs help ensure that a child receives the assistance he needs to reach educational goals based on his personal abilities. The child’s team of teachers, administrators, and parents typically update the IEP annually.

During teenage and adult years

For a teenager and adult with a 7q11.23 duplication, lifetime achievements will depend upon his or her level of intellectual disability. This is true for people with any genetic condition. For instance, being able to complete high school and hold a job are more likely to happen in those with no cognitive problems or those with milder intellectual disability. It is important to recognize that some people with this duplication have normal or above average intelligence and very successful careers.

Because 7q11.23 duplication syndrome follows an autosomal dominant inheritance pattern, each child born to a person with this diagnosis has up to a 1-in-2 (or 50%) chance of also having the duplication. When considering parenthood, it is important to remember that the type and severity of features can vary, even within members of the same family.

There have been many adults with this duplication reported in the medical literature. Their medical and developmental challenges are quite variable, though many of them reported language delay and a diagnosis of autism spectrum disorder or behavioral problems. Of note, life expectancy is predicted to be normal.

What can I do next?VIEW DETAILSHIDE DETAILS

It may be difficult for families to learn that a loved one has a genetic condition, and it is important to know that there are places you can go for support and medical care. Families may find it helpful to start with the following:

 Evaluations

  • When a genetic diagnosis of 7q11.23 duplication syndrome is made for a person, evaluation by a medical geneticist is recommended. A medical geneticist can help personalize each person's healthcare plan. Also, the medical geneticist can discuss additional testing or evaluations that may be considered, including testing for the duplication in other family members.
  • If there is concern for developmental delay or autism spectrum disorder, referral for age-appropriate services is warranted.
  • It may be helpful for people who have a 7q11.23 duplication and their family members to receive genetic counseling in order to discuss the finding, the recurrence risk, and reproductive options.
Treatment

There is no cure for 7q11.23 duplication syndrome. Treatment by various specialists should be provided based upon the specific challenges a person is having.

Currently, doctors are conducting research studies to learn more about 7q11.23 duplication syndrome. Families who are interested in research studies are encouraged to discuss these options with their child's doctor. Information about their studies can be found at:

http://louisville.edu/psychology/mervis/research/dup.html

Science

Although these references are very technical, we hope you find them useful. The goal of posting these references is not to overwhelm or discourage families and/or healthcare providers, but to make this information easily available as it is needed.

Reference 1

Title:  Speech delay and autism spectrum behaviors are frequently associated with duplication of the 7q11.23 Williams-Beuren syndrome region

Author:  Berg

Journal Name:  Genetics in Medicine

Volume:  9

Issue:  7

Publication Date:  7/1/2007

Page #:  427

Abstract:
Purpose: Williams-Beuren syndrome is among the most well-characterized microdeletion syndromes, caused by recurrent de novo microdeletions at 7q11.23 mediated by nonallelic homologous recombination between low copy repeats flanking this critical region. However, the clinical phenotype associated with reciprocal microduplication of this genomic region is less well described. We investigated the molecular, clinical, neurodevelopmental, and behavioral features of seven patients with dup(7)(q11.23), including two children who inherited the microduplication from one of their parents, to more fully characterize this emerging microduplication syndrome. Methods: Patients were identified by array-based comparative genomic hybridization. Clinical examinations were performed on seven affected probands, and detailed cognitive and behavioral evaluations were carried out on four of the affected probands. Results: Our findings confirm initial reports of speech delay seen in patients with dup(7)(q11.23) and further delineate and expand the phenotypic spectrum of this condition to include communication, social interactions, and repetitive interests that are often observed in individuals diagnosed with autism spectrum disorders. Conclusions: Array-based comparative genomic hybridization is a powerful means of detecting genomic imbalances and identifying molecular etiologies in the clinic setting, including genomic disorders such as Williams-Beuren syndrome and dup(7)(q11.23). We propose that dup(7)(q11.23) syndrome may be as frequent as Williams-Beuren syndrome and a previously unrecognized cause of language delay and behavioral abnormalities. Indeed, these individuals may first be referred for evaluation of autism, even if they do not ultimately meet diagnostic criteria for an autism spectrum disorder.

Reference 2

Title:  Severe expressive-language delay related to duplication of the Williams-Beuren locus.

Author:  Somerville

Journal Name:  New England Journal of Medicine

Volume:  353

Issue:  16

Publication Date:  10/20/2005

Page #:  1694

Abstract:
The Williams-Beuren syndrome (WBS) locus, at 7q11.23, is prone to recurrent chromosomal rearrangements, including the microdeletion that causes WBS, a multisystem condition with characteristic cardiovascular, cognitive, and behavioral features. It is hypothesized that reciprocal duplications of the WBS interval should also occur, and here we present such a case description. The most striking phenotype was a severe delay in expressive speech, in contrast to the normal articulation and fluent expressive language observed in persons with WBS. Our results suggest that specific genes at 7q11.23 are exquisitely sensitive to dosage alterations that can influence human language and visuospatial capabilities.

Support

If you are interested in learning more about a particular condition, or if you are interested in connecting with other families, here are some places you may want to start.

Unique: The Rare Chromosome Disorder Support Group


    
Unique

Duplication Cares


    
Duplication Cares