Chromosome 15q11.2–13.1 Duplication Syndrome (OMIM #608636) “Dup15q Syndrome” is a clinically identifiable syndrome that results from the duplication (or multiplication) of a portion of chromosome 15.
There are many other genetically derived names that are commonly used in the diagnosis for dup15q syndrome, including;
- 15q11.2-q13.1 duplication syndrome
- Inverted duplication 15 (inv dup15)
- Partial trisomy 15
- Isodicentric chromosome 15 syndrome [Idic(15)]
- Supernumerary marker chromosome 15 (SMC15)
- Partial tetrasomy 15q
Dup15q syndrome is caused by the presence of at least one extra copy of the Prader-Willi/Angelman critical region (PWACR) within chromosome 15q11.2-13.1. It can span past these bands but must contain the 11.2 – 13.1 region to be identified as dup15q syndrome.
Dup15q syndrome is one of the most common copy number variations associated with autism spectrum disorders, intellectual disability, and infantile spasms. Infantile spasms in dup15q often progress to Lennox Gastaut syndrome and other complex seizure patterns that may be difficult to control. Intractable epilepsy in dup15q may result in disabling secondary effects, including falls or developmental regression. This occurs in more than half of individuals with frequent, uncontrolled seizures or non-convulsive status epilepticus.
It is important to note there is a wide range of severity in the developmental disabilities experienced by individuals with dup15q syndrome.
- Minor Unusual Physical Features
- Downslanting palpebral fissures
- Moderate-to-Severe Hypotonia
- Wide-based or Ataxic Gait
- Growth affected in 20–30% resulting in small stature
- Low-set ears
- High-arched palate
- Dental Issues
These features are typically subtle and may be missed in infancy.
- Cognitive Disability
- Motor Delays
- Speech Delay
- Learning disabilities
- Seizure Disorders
- Infantile Spasms
- Developmental Epileptic Encaphaly
- Over half of the dup15q population will have at least 1 seizure
- Increased Risk for Sudden Death
- The risk is small, estimated at 0.5-1% per person per year.
- Sleep Disturbances
- Gastrointestinal Issues
- Autism Spectrum Disorder/Autism Symptomology
- Sensory Processing Disorders
- Attention Deficit Disorders
- Anxiety Disorders
Patients with dup15q syndrome have shown abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls.
Both of these EEG disturbances are in the absence of seizures.
Compared to children with nonsyndromic ASD, children with dup15q-ASD demonstrate a distinctive behavioral profile with relative strength in items related to social interest, including preserved responsive social smile and directed facial expressions towards others.
The diagnosis of maternal dup15q is established by detection of at least one extra maternally derived copy of the Prader-Willi/Angelman critical region, a region approximately 5 Mb long within chromosome region 15q11.2-q13.1. The extra copy or copies most commonly arise by one of two mechanisms:
A maternal isodicentric 15q11.2-q13.1 supernumerary chromosome – idic(15) – typically comprising two extra copies of 15q11.2-q13.1 and resulting in tetrasomy for 15q11.2-q13.1 (~60-80%);
Maternal dup15q caused by:
Maternal idic(15). De novo in all affected individuals reported to date; thus, risk to sibs is low, but presumed to be marginally greater than in the general population because of the possibility of maternal germline mosaicism;
Maternal interstitial 15q11.2-q13.1 duplication. De novo in approximately 85% of probands and inherited from the mother in approximately 15%. If the mother has the 15q interstitial duplication, the risk to each child of inheriting the duplication is 50%.
Prenatal testing or preimplantation genetic testing using chromosomal microarray (CMA) will detect the 15q interstitial duplication; however, prenatal test results cannot reliably predict the severity of the phenotype even in a pregnancy known to be at increased risk for maternal dup15q.