15q13.3 microduplication syndrome

The first signs of 15q13.3 microduplication syndrome may be present in infancy or early childhood. These may include not meeting developmental milestones such as sitting, standing, or walking, at the ages other children do (developmental delay). In some cases, children also have low muscle tone (hypotonia). Some children with the syndrome begin speaking later than other children (speech delay) or have trouble communicating. Infants with 15q13.3 microduplication syndrome have difficulty feeding, and children may want to eat more food than they need (overeating) as they get older.^[1][4]

People with 15q13.3 microduplication syndrome may have intellectual disability. In most cases, intellectual disability is mild if it is present, but some people with the syndrome have had more severe intellectual disability. People with the syndrome are more likely to have behavioral challenges including autism, attention difficulties, and schizophrenia.^[1][5]  

Some children with 15q13.3 microduplication syndrome struggle to sleep at night (insomnia). Other health problems that may be associated with the syndrome include having multiple seizures (epilepsy).^[1] One study found that 15q13.3 microduplication syndrome may be associated with cleft lip or palate.^[2]

The problems associated with 15q13.3 microduplication syndrome can vary widely, even among members of the same family. This concept is called variable expressivity. In some cases, people who have 15q13.3 microduplication syndrome may not have any medical, developmental, or behavioral problems related to the syndrome. This concept is called reduced penetrance.^[1] Because only a small number of people with 15q13.3 microduplication syndrome have been reported, it is not known if there are other medical, developmental, or behavioral problems that may be associated with the syndrome.^[1][4]

15q13.3 microduplication syndrome is caused by having an extra piece of genetic information (duplication) on one of the chromosomes. Most people have 46 chromosomes in each cell of the body, and the chromosomes come in pairs. Therefore, there are two copies of chromosome 15. People with 15q13.3 microduplication syndrome have an extra copy of a small piece of chromosome 15. Specifically, this duplicated piece is on the long arm (called the q arm) of chromosome 15. The duplication is thought to contain at least six genes in most people who have the syndrome.^[1]

It is thought that changes in one of the genes in the region, called CHRNA7, may cause an increased risk for seizures or behavioral problems.^[1][4][6] However, in general it is not known exactly why the extra genetic information on chromosome 15 can cause medical, developmental, and behavioral problems. It is also not known exactly why there can be such a wide range of problems associated with the syndrome, with some people not having any problems at all. It is possible that other genetic or environmental factors influence the problems that each person with the syndrome has.^[1]

People with 15q13.3 microduplication syndrome may have inherited the syndrome from a parent, or they may be the first in the family to have the syndrome. When the syndrome is inherited from a parent, it is inherited in an autosomal dominant manner. In some cases, the parent may have only mild medical, developmental, or behavioral problems associated with the duplication, or the parent might not have any features of the syndrome at all.^[1] When a person with 15q13.3 microduplication syndrome has children, for each child there is a:

• 50% chance to inherit the copy of chromosome 15 that has the microduplication
• 50% chance to inherit the copy of chromosome 15 that does not have the microduplication

Because the problems associated with 15q13.3 microduplication syndrome can vary, the exact medical, developmental, or behavioral problems that a child with the duplication will have is not possible to predict.^[1]

In some cases, people with 15q13.3 microduplication syndrome are the first people in their families to have the duplication, and it is not inherited from either parent. When a duplication is new in a person and is not inherited from either parent, it is called de novo.^[1]

The medical, developmental, and behavioral problems caused by 15q13.3 microduplication syndrome are very similar to problems caused by other chromosome disorders or other genetic syndromes. Therefore, when a child has a number of medical, developmental, or behavioral problems, a doctor may suspect that there could be a chromosome disorder and will first order a genetic test called a chromosomal microarray (CMA). This test looks for extra or missing pieces of chromosomes. Most people who are diagnosed with 15q13.3 microduplication syndrome had a CMA completed based on signs such as feeding problems, developmental delay, or behavioral problems.^[1]

Treatment for 15q13.3 microduplication syndrome typically includes physical, occupational, and speech therapies. Children with the syndrome may require extra help in school or other therapies to help manage behavioral challenges such as autism. These therapies may help people with the syndrome reach their full potentials.^[1]

Other treatments that may be recommended for people with 15q13.3 microduplication syndrome include antiepileptic drugs to treat seizures. Melatonin may be recommended to help children with difficulty sleeping (insomnia) sleep at night.^[1] 

The long-term outlook for people with 15q13.3 microduplication syndrome is generally good. Other than some medical problems that may cause feeding difficulties or seizures (epilepsy), people with the syndrome are generally healthy.^[1] Treatment options such as therapies may be helpful in allowing people with the syndrome to reach their full potentials. Based on current understanding of 15q13.3 microduplication syndrome, it is expected that people with the syndrome will have a normal lifespan.^[1]