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15q13.3 microdeletion 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 15q13.3 microdeletion syndrome?VIEW DETAILSHIDE DETAILS

15q13.3 microdeletion syndrome is a condition caused by a loss of genetic material, also called a deletion, on chromosome 15. There is no cure for this condition, but having a diagnosis can help guide a person’s health care. In addition, having a diagnosis of 15q13.3 microdeletion syndrome in one family member allows for targeted testing of at-risk family members.
Features

15q13.3 microdeletion syndrome is a genetic condition that has been associated with many symptoms. However, not all people with this condition will have all of the symptoms, and those symptoms vary in severity from person to person (variable expressivity). Additionally, some people with the microdeletion may not have any symptoms at all (non-penetrance). In other words, having this microdeletion leads to a predisposition for certain symptoms.

The symptoms that are more likely to occur in someone with 15q13.3 microdeletion syndrome than in someone without the condition are intellectual disability, seizures, autism spectrum disorder, neuropsychiatric disorder, and subtle, unique physical features.

If a person with 15q13.3 microdeletion syndrome has intellectual disability, it is usually in the mild to moderate range (this was previously known as mild to moderate mental retardation). If a person has seizures, they may be either mild or severe, and may respond well to medication though this is difficult to predict. It is also possible for a person with this condition to have an abnormal brain wave study (electroencephalogram or EEG) with or without seizures.

If a person with 15q13.3 microdeletion syndrome has autism spectrum disorder, it may be mild or severe. This has been characterized by delayed speech development, limited eye contact, and social withdrawal. If a person has neuropsychiatric disorder, it may be mild or severe. Individuals with 15q13.3 microdeletion syndrome have been reported to have bipolar disorder, and others have been reported to have schizophrenia.

If a person with 15q13.3 microdeletion syndrome has subtle, unique physical features, it may be difficult for anyone other than a genetic specialist to recognize them. Individuals with with 15q13.3 microdeletion syndrome have been reported to have facial features that are different from other family members and subtle, unusually shaped fingers.

It is difficult to predict the chance for a person with 15q13.3 microdeletion syndrome to experience each of these associated symptoms. As more people are diagnosed, and as the parents of that person are tested, we may gain a better understanding of how many people have the microdeletion, and what percentage of those people have each of the associated symptoms.

Statistics

15q13.3 microdeletion syndrome is a rare condition that has only recently been characterized; therefore it is difficult to pinpoint just how often it occurs. This is because there is a wide range of disability (variable expressivity), and some people with milder symptoms may not be diagnosed. Additionally, some people with the microdeletion may not have any symptoms at all (non-penetrance). 15q13.3 microdeletion syndrome affects males and females of all ethnic backgrounds. It is estimated to occur in one out of 15,000 people.

How did this happen?VIEW DETAILSHIDE DETAILS

The cause of 15q13.3 microdeletion syndrome is a loss of genetic material, or a deletion, of one or more genes on one copy of chromosome 15. It is thought that this microdeletion is inherited from one of the parents in at least 50% of cases. Additionally, the microdeletion may be new in the child (de novo). The presence of 15q13.3 microdeletion syndrome, whether inherited or de novo, is not caused by anything the parents did before or during the pregnancy.

Can this happen again?VIEW DETAILSHIDE DETAILS

It is important to know how a diagnosis of 15q13.3 microdeletion syndrome could affect other children in the family. For instance, most parents wonder what the chance is for their next child to have the same diagnosis (recurrence risk).

In order to best answer this question, the parents should likely undergo genetic testing to determine if either of them have the microdeletion found in the child. If genetic testing shows a parent has the microdeletion, there would be a 1-in-2 (or 50%) chance for every other child to have the same microdeletion. This is because 15q13.3 microdeletion syndrome follows an autosomal dominant inheritance pattern. Remember, two people with the microdeletion, even those within the same family, may have varying types and degrees of symptoms, including the possibility for no symptoms at all.

If genetic testing shows that neither parent has the microdeletion, there is less than a 1% chance for other children in the family to have the microdeletion. However, there are no guarantees that another child will not have the same or similar symptoms .

Who else should be tested?VIEW DETAILSHIDE DETAILS

When a person is diagnosed with 15q13.3 microdeletion syndrome, his or her parents may want to consider targeted genetic testing for themselves. This could clarify recurrence risk and help identify at-risk family members. Testing could be done on a blood sample for the presence of the microdeletion. If either parent has the microdeletion, other children in the family would be at-risk. If children who are at-risk have symptoms, testing for the microdeletion may be warranted. In the absence of symptoms, children who are at-risk may want to consider testing when planning their own reproductive future. It may be helpful for the family to speak with a genetic counselor or medical geneticist to discuss further testing options.

What can I expect?VIEW DETAILSHIDE DETAILS

This section is meant to be a guide for some of the more common features that may arise in a person with 15q13.3 microdeletion syndrome. Someone 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 are no signs or symptoms during pregnancy that indicate a developing baby has 15q13.3 microdeletion syndrome.

As a newborn and infant

Newborns with 15q13.3 microdeletion syndrome may not have any signs or symptoms that cause a health care provider or parent to suspect the condition. They usually have a normal height/length and weight and generally do not have any birth defects or major health problems.

Some infants have early signs of intellectual disability, which may include delays in reaching developmental milestones. These are more often related to socialization and language development rather than gross motor milestones. Also, infants may have difficulty coordinating sucking, swallowing, and feeding, which could lead to slow weight gain. Some infants have low muscle tone (hypotonia), which can contribute to these problems.

It is possible for infants with 15q13.3 microdeletion syndrome to develop seizures. There are many seizure types, and these may be obvious or subtle, and may respond well to medications. If there are concerns for seizures, a neurologist can help evaluate the child and manage a treatment plan. If a child with the condition does not have seizures during infancy, it is still possible for him or her to develop seizures later in life.

During childhood years

A child with 15q13.3 microdeletion syndrome may have subtle, unique physical features that are noticeable during childhood. For example, some children have been reported to have widely spaced eyes that slant upward, bushy or thick eyebrows, full lips, and short, curved pinky fingers. These features do not generally cause medical problems, but may lead health care providers and parents to suspect that the child has an underlying medical condition. However, most people are not able to identify a child has having 15q13.3 microdeletion syndrome based upon these features.

Health care providers and parents may begin to notice more striking differences in the child around the time when language development should be happening. For example, many children with 15q13.3 microdeletion syndrome do learn to talk, but it may take them several years longer than expected. Other features that raise concern for an autism spectrum disorder include social withdrawal or the child’s desire to play alone, repetitive behaviors, and limited eye contact.

Many parents report that their child with 15q13.3 microdeletion syndrome has unique behavioral patterns. This may include attention deficit hyperactivity disorder or ADHD, aggression, and early signs of neuropsychiatric disorder such as obsessive behaviors, anxiety, and mood disorders.

A child with 15q13.3 microdeletion syndrome who has intellectual disability may require extra attention in the school setting. For these reasons, as well as the possibility for behavioral problems, a child with this condition should have a neurodevelopmental assessment through early intervention services or through the school system. Early intervention services are typically available through state programs when a child is young (usually up to three years of age, but check with your local provider or school district). After that time, the school system should provide assessments that will help to create an individualized education program or IEP. IEPs are updated yearly by the child’s team of teachers, administrators, and parents. IEPs help ensure that a child receives the assistance he or she needs to reach educational goals based on his or her personal abilities.

During teenage and adult years

Because parents of children with 15q13.3 microdeletion syndrome have also been reported to have the microdeletion, there is reason to believe that both males and females with the condition go through puberty around the same time as would be expected in those without the condition. Because individuals with this condition are able to have children, it is important to know how those children could be affected. Because 15q13.3 microdeletion syndrome follows an autosomal dominant inheritance pattern, each child born to a person with the microdeletion has a 1-in-2 (or 50%) chance of also having the microdeletion. Remember, the severity of the condition can vary between parent and child, and some people with the microdeletion may not have any symptoms.

For an adult with 15q13.3 microdeletion syndrome, lifetime achievements will depend upon his or her level of intellectual disability. For instance, being able to complete high school (generally with some special education or resource assistance), go to a vocational training program, hold a job, and live independently are all possible, but happen more often in those with no or mild intellectual disability.

Because there is an association between 15q13.3 microdeletion syndrome and neuropsychiatric disorder such as bipolar disorder and schizophrenia, it is important for those with concerning symptoms to seek professional medical attention.

Overall, the life expectancy for people with 15q13.3 microdeletion syndrome is normal, provided there are no major complications with a seizure disorder or symptoms of severe neurological impairment.

What can I do next?VIEW DETAILSHIDE DETAILS

It may be difficult for parents and families to learn that a loved one may have a genetic condition, but reaching a diagnosis is an important first step to giving their child the health care and support that may be needed.
Evaluations

There are currently no nationally recognized consensus guidelines for medical and developmental interventions in people with 15q13.3 microdeletion syndrome. It is strongly recommended that people with this condition meet with a medical geneticist to coordinate any necessary follow up evaluations and to create a personalized medical management plan. Families may find it helpful to start with the following:

  • If a child with 15q13.3 microdeletion syndrome has not been evaluated or is not receiving therapies, families are encouraged to contact the local early intervention program, a developmental pediatrician, or the school district. In general, early intervention services are available up to three years of age, but check with your local provider or school district. After that time, a developmental pediatrician or the school system should provide assessments. This will help ensure that a child receives therapies and an individualized education program (IEP) as needed.
  • A person with 15q13.3 microdeletion syndrome should meet with a medical geneticist. A medical geneticist can help to coordinate any necessary follow up evaluations and to create a personalized medical management plan. A medical geneticist can also guide testing for additional family members, as appropriate.
  • It may be helpful for families to receive genetic counseling in order to discuss the condition, the recurrence risk, and reproductive options.

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:  Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders.

Author:  Miller

Journal Name:  Journal of Medical Genetics

Volume:  46

Issue:  4

Publication Date:  4/1/2009

Page #:  242

Abstract:
BACKGROUND: Segmental duplications at breakpoints (BP4-BP5) of chromosome 15q13.2q13.3 mediate a recurrent genomic imbalance syndrome associated with mental retardation, epilepsy, and/or electroencephalogram (EEG) abnormalities. PATIENTS: DNA samples from 1445 unrelated patients submitted consecutively for clinical array comparative genomic hybridisation (CGH) testing at Children's Hospital Boston and DNA samples from 1441 individuals with autism from 751 families in the Autism Genetic Resource Exchange (AGRE) repository. RESULTS: We report the clinical features of five patients with a BP4-BP5 deletion, three with a BP4-BP5 duplication, and two with an overlapping but smaller duplication identified by whole genome high resolution oligonucleotide array CGH. These BP4-BP5 deletion cases exhibit minor dysmorphic features, significant expressive language deficits, and a spectrum of neuropsychiatric impairments that include autism spectrum disorder, attention deficit hyperactivity disorder, anxiety disorder, and mood disorder. Cognitive impairment varied from moderate mental retardation to normal IQ with learning disability. BP4-BP5 covers approximately 1.5 Mb (chr15:28.719-30.298 Mb) and includes six reference genes and 1 miRNA gene, while the smaller duplications cover approximately 500 kb (chr15:28.902-29.404 Mb) and contain three reference genes and one miRNA gene. The BP4-BP5 deletion and duplication events span CHRNA7, a candidate gene for seizures. However, none of these individuals reported here have epilepsy, although two have an abnormal EEG. CONCLUSIONS: The phenotype of chromosome 15q13.2q13.3 BP4-BP5 microdeletion/duplication syndrome may include features of autism spectrum disorder, a variety of neuropsychiatric disorders, and cognitive impairment. Recognition of this broader phenotype has implications for clinical diagnostic testing and efforts to understand the underlying aetiology of this syndrome.

Reference 2

Title:  Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders.

Author:  Ben-Shachar

Journal Name:  Journal of Medical Genetics

Volume:  46

Issue:  6

Publication Date:  6/1/2009

Page #:  382

Abstract:
BACKGROUND: Microdeletions within chromosome 15q13.3 are associated both with a recently recognised syndrome of mental retardation, seizures, and dysmorphic features, and with schizophrenia. METHODS AND RESULTS: Based on routine diagnostic testing of approximately 8200 samples using array comparative genomic hybridisation, we identified 20 individuals (14 children and six parents in 12 families) with microdeletions of 15q13.3. Phenotypes in the children included developmental delay, mental retardation, or borderline IQ in most and autistic spectrum disorder (6/14), speech delay, aggressiveness, attention deficit hyperactivity disorder, and other behavioural problems. Both parents were available in seven families, and the deletion was de novo in one, inherited from an apparently normal parent in four, and inherited from a parent with learning disability and bipolar disorder in two families. Of the 14 children, six in five families were adopted, and DNA was available for only one of these 10 biological parents; the deletion was very likely inherited for one of these families with two affected children. Among the unavailable parents, two mothers were described as having mental retardation, another mother as having "mental illness", and one father as having schizophrenia. We hypothesise that some of the unavailable parents have the deletion. CONCLUSIONS: The occurrence of increased adoption, frequent autism, bipolar disorder, and lack of penetrance are noteworthy findings in individuals with deletion 15q13.3. A high rate of adoption may be related to the presence of the deletion in biological parents. Unconfirmed histories of antisocial behaviours in unavailable biological parents raise the concern that future research may show that deletion 15q13.3 is associated with such behaviours.

Reference 3

Title:  A 15q13.3 microdeletion segregating with autism.

Author:  Pagnamenta

Journal Name:  European Journal of Human Genetics

Volume:  17

Issue:  5

Publication Date:  5/1/2009

Page #:  687

Abstract:
Autism and mental retardation (MR) show high rates of comorbidity and potentially share genetic risk factors. In this study, a rare approximately 2 Mb microdeletion involving chromosome band 15q13.3 was detected in a multiplex autism family. This genomic loss lies between distal break points of the Prader-Willi/Angelman syndrome locus and was first described in association with MR and epilepsy. Together with recent studies that have also implicated this genomic imbalance in schizophrenia, our data indicate that this CNV shows considerable phenotypic variability. Further studies should aim to characterise the precise phenotypic range of this CNV and may lead to the discovery of genetic or environmental modifiers.

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.

Chromosome Disorder Outreach (CDO)

P.O. Box 724
Boca Raton  Florida  33429-0724
Chromosome Disorder Outreach (CDO)

Unique: The Rare Chromosome Disorder Support Group

P.O. Box 2189
Caterham Surrey CR3 5GN, United Kingdom    
Unique: The Rare Chromosome Disorder Support Group