17q12 Duplication Syndrome

Genetics

17q12 duplication syndrome is caused by an extra piece of chromosome 17 (microduplication) that is present from the moment the child is conceived. There are many different microduplications that can occur on chromosome 17, but 17q12 duplication syndrome is caused by a duplication of a specific ~1.4Mb region on the long arm (“q arm”) of chromosome 17 at position 12 (one-two). The most common test used to identify the duplication is called a chromosomal microarray (CMA). The duplication is too small to be detected with a karyotype. Based on current research, about 1 in 2,500 individuals in the general population have the duplication syndrome. It is more common in populations with developmental disorders (developmental delay, autism, intellectual disability) and schizophrenia.

Inheritance

The duplication is most often inherited from a parent. Oftentimes, the parent is only identified after the child is diagnosed and could have similar, milder or apparently no features. In these cases, there is a 50% chance (1 in 2) that each of that parent’s children will also have the duplication. About 10% of the time, or 1 in 10 people with the duplication will have a brand new (de novo) duplication that was not inherited from either parent. If it was de novo (both parents tested negative), then the chances that a sibling has it is lower than 1%.

Clinical Features

A syndrome is defined as a recognizable group of signs and symptoms that consistently occur together. The most common features of the duplication are related to neurodevelopment. It is important to remember that no two people with the duplication will have the same combination and/or severity of symptoms, even people within the same family.

Neurodevelopmental: intellectual abilities ranging from typical to severe disability, speech delay, motor delay, behavioral concerns (aggression, compulsive disorders), autism spectrum disorder
Seizures in up to 75% of individuals
Microcephaly (small head size)
Hypotonia (low muscle tone)
Skeletal differences

Some features have been reported less commonly including:

Heart defects
Eye/Vision problems: strabismus (crossed eye), astigmatism, amblyopia (lazy eye), small eyes
Kidney abnormalities: horseshoe kidney, cysts, underdeveloped kidneys
Tracheoesophageal fistula (an abnormal connection between the windpipe and the tube that leads from the throat to the stomach)

Overall, there have been relatively few individuals reported in the literature with the duplication. Additionally, due to the frequency that the duplication is identified in a mildly or unaffected parent, the associated clinical features and frequencies reported to date are likely to change as new information is learned through research.