Chromosome 15q11.2-13.1 duplication syndrome (dup15q) is a clinically identifiable syndrome which results from duplications of chromosome 15q11.2-q13.1. Chromosome 15q duplications are associated with autism spectrum disorders, developmental delay, learning disabilities/cognitive delays, and seizures/epilepsy.
Clinicians should suspect this syndrome in any infant/child with early central hypotonia, minor dysmorphic features, significant developmental delay, autistic behaviors, infantile spasms or who subsequently develops hard to control seizures/epilepsy.
Chromosome 15q duplications most commonly occur in one of two forms, either as an extra isodicentric 15 chromosome or as an interstitial duplication of chromosome 15q.
Isodicentric chromosome 15, abbreviated idic(15), is diagnosed in individuals who have 47 chromosomes (or sometimes more) instead of the typical 46 chromosomes. The extra chromosome is made up of a portion of chromosome 15 that has been duplicated and "inverted," so that there are two copies of part of chromosome 15q attached to one another that appear to be mirror images. Because of this arrangement, idic(15) used to be referred to as "inverted duplication chromosome 15." Most commonly, the region called 15q11-q13 is the portion of chromosome 15 duplicated. Sometimes the duplicated region is larger. The size of the idic(15) varies depending on the size of the region of chromosome 15 that is duplicated.
People born with the typical 46 chromosomes, but who have a segment of duplicated material within chromosome 15, are said to have an interstitial duplication chromosome 15. Most often this is the same section (15q11-q13) that makes up the extra chromosome in idic(15). For this reason, people with interstitial duplications of 15q and those with idic(15) share similar characteristics. As a group however, people with interstitial duplication 15 tend to have milder symptoms than those with idic(15).
When the extra genetic material comes from the paternal chromosome, a child may have normal development. However, when the duplicated material comes from the maternal chromosome, developmental problems are often the result. In most cases of chromosome 15q11.2-13.1 duplication syndrome, the chromosome duplication is not inherited, but occurred as a random event during the formation of reproductive cells (eggs and sperm).
Diagnosis is confirmed by standard cytogenetic techniques and FISH analysis, which confirms the diagnosis by distinguishing the dup15q from other supernumerary marker chromosomes. Interstitial duplications of chromosome 15 can be more difficult to detect on a routine chromosome analysis but are clearly identifiable using a 15q FISH study or clinical microarray/array CGH. Molecular studies, such as microsatellite analysis on parental DNA or methylation analysis on the affected child’s DNA, are required in order to detect the parent-of-origin of the dup15q. Families should always discuss the results of DNA tests, chromosome and FISH studies with a genetic counselor or other genetics professional to ensure accurate interpretation.
There is a wide range of severity in the developmental problems experienced by individuals with dup15q syndrome. Two children with the same dup15q chromosome pattern may be very different in terms of their abilities. Reviews of the scientific literature do not show an obvious correlation between the size of the duplication region and the severity of the symptoms. The following sections provide information on physical features, developmental problems, medical issues and treatments for chromosome 15q duplications.