Isodicentric 15

There are two main types of idic (15). Type 1 has the more obvious features and usually contains two extra copies of the so-called Prader-Willi-Angelman critical region (PWACR) on chromosome 15. This region may be deleted in patients with Prader-Willi or Angelman syndrome. Except in very rare circumstances, people with idic (15) do not have Prader-Willi or Angelman syndrome. It is the presence of this extra genetic material that is thought to account for the symptoms seen in individuals with this disorder. Those with type 2 do not have extra copies of the PWACR. Type 2 is not usually associated with any problems but, unlike type 1, it is often passed down through a family.

The features associated with type 1 idic (15) are ‘non-specific’; in other words, they tend not to form an easily recognisable syndrome (pattern), and they are seen in a range of other disorders. The most common features are:

• hypotonia (reduced muscle tone). This is often present at birth but usually decreases with age. Babies may appear ‘floppy’ and have difficulty sucking. Motor milestones (rolling over, sitting up and walking) may be delayed, but most individuals are able to walk independently
• seizures (see entry Epilepsy). Many, but not all, affected children and adults have seizures at some point in their lives. These may be occasional or frequent, short or prolonged
• developmental delay (see entry Learning Disability). Learning difficulties vary in severity but are often moderate to severe.

Autistic behaviours (see entry Autism Spectrum conditions) are also associated with idic (15), including hand flapping, poor eye contact, repetitive or poorly developed speech and a need for ‘sameness’ in environment or daily routine. Many share similar facial characteristics including a flattened nasal bridge giving a ‘button’ nose, skin folds, called ‘epicanthi’ at the inner corners of the eyes, downward slanting eyes and full lips.

Individuals with idic (15) have an extra chromosome made up of some material from the 15th pair of chromosomes. This means that there are forty-seven chromosomes (or occasionally forty-eight or forty-nine) in these cells rather than 46. The extra piece of chromosome 15 has been duplicated end-to-end like a mirror image and is referred to as an ‘isodicentric 15’, an ‘inverted duplication 15’, or a ‘supernumerary marker.’

Distinguishing between the two types of idic (15) is important. Most laboratories now use a technique called array comparative genomic hybridization (aCGH) as the front line test (replacing the karyotype) in patients presenting with the clinical features associated with idic (15). This test will show how much extra chromosome material is present and so distinguish between the two types. FISH (fluorescent in situ hybridisation) follow up studies will still be essential to accurately diagnose idic (15) chromosomes when an imbalance is detected by aCGH.

Treatment is tailored to the individual, and will be based on the features displayed.

Inheritance patterns
Type 1 idic (15) almost always occurs sporadically. In other words, no other family member, brother or sister, is usually affected. However, type 2 idic (15) can be inherited. Genetic advice and counselling should be sought.

Prenatal diagnosis
This is rarely carried out specifically to look for idic (15); however, the diagnosis may be made for the first time by examination of chorionic villus samples (CVS) or amniotic fluid taken for Down syndrome screening. If the idic (15) anomaly is identified, expert advice should be sought.

Information and support in the UK for isodicentric 15 is provided by Unique (see entry Chromosome Disorders).