15q11-q13 duplication syndrome (Dup15q) - Chromosome 15

15q11-q13 duplication syndrome, also known as dup15q syndrome or isodicentric chromosome 15 syndrome, is a developmental disorder with variable signs and symptoms. Affected individuals may suffer from hypotonia, which can lead to feeding difficulties, developmental delay, impaired motor skills, and an ataxic gait; from mild to profound intellectual disability; difficulties or absence in the development of speech and language, and language problems such as ecolalia or stereotyped expressions; autism spectrum alterations; hyperactivity, anxiety, mood disorders and psychosis; and recurrent seizures, which frequently include focal seizures, myotonic seizures, tonic-clonic seizures, absence seizures and, in less common cases, Lennox-Gastaut syndrome.

Other common features in affected individuals include temporary hearing loss; squint; unusual facial features such as palpebral fissures tilted down, a flattened nasal bridge with a short and upward nose, nostrils that open to the front instead of down, micrognathia, thick lips, and low-implanted ears. In addition, individuals with dup15q syndrome may have a reduced ability to feel pain; scoliosis; recurrent respiratory infections in childhood; eczema; precocious puberty and, in women, menstrual irregularities; and minor genital anomalies in men, such as cryptorchidism.

This process is due to chromosomal abnormalities that give rise to at least one additional copy of the 15q11.2-q13.1 region of chromosome 15. In particular, the condition arises only if the chromosomal abnormality occurs in the maternal copy. People usually inherit a copy of chromosome 15 from each parent. However, some genes on this chromosome, including some in the 15q11.2-q13.1 region, are active only in the maternal copy. The most frequent chromosomal abnormality, which occurs in approximately 80 percent of people with dup15q syndrome, is called an isodicentric chromosome 15. An isodicentric chromosome contains specular image segments of genetic material and has two centromeres, instead of a centromere as in normal chromosomes In people with an isodicentric chromosome 15, the cells have the usual two copies of chromosome 15 plus the two duplicate copies of the segment of genetic material on the isodicentric chromosome, for a total of four copies of the duplicated segment. In approximately 20 percent of cases of dup15q syndrome, duplication occurs in the long arm of one of two copies of chromosome 15 in each cell. This situation is called interstitial duplication. In these cases, the cells have two copies of chromosome 15, one of which has an additional copy of the genetic material segment, for a total of three copies of the duplicated segment.

In all cases of dup15q syndrome, the duplicated genetic material produces additional copies of certain genes involved in development. This additional genetic material alters normal development, giving rise to the characteristic features of this disease. Usually, people with dup15q syndrome due to interstitial duplication have milder signs and symptoms than in those who develop the disease as a result of an isodicentric chromosome 15.

The 15q11-q13 duplication syndrome due to an isodicentric chromosome 15 is generally not inherited. This process is usually due to a chromosomal change that occurs as a random event during the formation of the ovules in the mother of the affected individual, so most of the affected individuals have no history of the disease in their family. In 15 percent of cases due to interstitial duplication, the alteration is inherited from a mother who also has the duplication. The rest of the cases are due to a new duplication of the genetic material.

Tests performed in IVAMI: in IVAMI we perform the study of duplications on chromosome 15, by means of quantitative real-time PCR.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).