Chromosome 15q11.2-13.1 duplication syndrome (dup15q syndrome) is a clinically identifiable syndrome which results from duplications of chromosome 15q11.2-13.1. These duplications most commonly occur in one of two forms. These include an extra isodicentric 15 chromosome, abbreviated idic(15), or an interstitial duplication 15, abbreviated int dup(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) or during early embroyonic development.
It is important to acknowledge that there is a wide range of severity in the developmental disabilities experienced by individuals with chromosome 15q11.2-13.1 duplication syndrome. Two individuals 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. However, the following features are found to some degree in most individuals with dup15q syndrome.
Since chromosomes carry genes that determine how our bodies grow and develop, having extra chromosomal material can alter a person’s physical development. Unlike many other chromosomal syndromes, there are few characteristic physical findings associated with chromosome 15q11.2-13.1 duplication syndrome. The physical findings are fairly non-specific and may include the following:
Babies with dup15q syndrome usually have hypotonia (poor muscle tone). They may appear "floppy" and have difficulty sucking and feeding. Some parents report that their babies with dup15q syndrome have an unusual, weak cry. Motor milestones such as rolling over, sitting up, and walking are significantly delayed. Older children and adults with hypotonia often tire easily. Hypotonia in dup15q syndrome generally decreases with age and sometimes progresses to hypertonia (tight muscle tone) particularly in the lower legs.
Many individuals with dup15q syndrome share similar facial characteristics. These include a flat nasal bridge which gives them a "button" nose. There may be skin folds, called "epicanthic", at the inner corners of the eyes, and the eyes may be deep set. Ears may be low-set and/or posteriorly rotated. There may also be noticeable unfolding of the edge of the ears. The palate (roof of the mouth) may be unusually high. There are also reports of areas of increased and reduced skin pigmentation.
Growth is affected in about 20–30% of individuals with dup15q syndrome, resulting in small stature. Although puberty appears to be normal in most individuals, pubertal disorders such as central precocious puberty have been observed in some girls.
Rarely, babies with dup15q syndrome may be born with a cleft lip and/or palate or differences in the way their hearts, kidneys, or other body organs are formed. For this reason, it is important for newly diagnosed children with dup15q syndrome to be carefully evaluated for the possibility of such structural differences. Check with your genetics specialist for specific recommendations.
Due to the hypotonia experienced by young children with dup15q syndrome, gross motor delays are very common. In a 2005 scientific review article, sitting was reportedly achieved between 10 and 20 months of age, and walking between 2 and 3 years. A study of children with dup15q syndrome found that those with isodicentric duplications achieved independent walking at an average of 25.5 months (range 13-54 months), with 3 children (out of 47) who were not ambulatory at the time of testing. The vast majority of individuals with dup15q syndrome are able to walk independently.
Parent reports suggest that fine motor delays are widespread among children with dup15q syndrome. Nonfunctional use of objects with an immature type of exploration has been reported in the scientific literature.
Most individuals with dup15q syndrome show some degree of cognitive delay/disability from very early on. These cognitive disabilities are often associated with behavioral problems as children age.
There are now over 20 reports in the literature of individuals with both autism and idic(15). Two studies that included a total of 226 patients with autism found dup15q syndrome in approximately 3-5% of the patients. Chromosome 15q11–13 duplications are the most frequently identified chromosomal problem in individuals with autism.
Most children with dup15q syndrome are affected by speech/language delays. Expressive language may be absent or may remain very poor, and is often echolalic with immediate and delayed echolalia and pronoun reversal. In her study of dup15q syndrome, Dr. Carolyn Schanen found 26 of 47 children had some language at the time of their participation in the research study, with the first word achieved at an average of 28.7 months (range 7-84 months) and phrase speech beginning by an average of 44.1 months (range 9-114 months). While the majority of children with dup15q syndrome experience speech delays, some children are highly verbal.
Parent reports suggest that sensory processing disorders are widespread in dup15q syndrome. These sensory processing disorders disrupt the affected child’s ability to achieve and maintain an optimal range of arousal and to adapt to challenges in daily life. These disorders are often manifested by an over-responsiveness or under-responsiveness to sensory input or fluctuations in response to sensory input.
Many individuals with dup15q syndrome have difficulties of behavior and social communication, with a lack of response to social cues frequently observed. In older individuals, there is some suggestion of improving social awareness with age.
Seizures represent an important medical feature of dup15q syndrome. Over half of all people with idic(15) will have at least one seizure. The majority of those will experience their first seizure before age 5, but seizure onset occurs up through puberty and young adulthood in this population. There are many different types of seizures experienced by individuals with dup15q syndrome. Affected individuals may start with one seizure type, with other types emerging as the individual ages. Response to treatment is variable. Some seizures are easily controlled with the first medication, other seizures are controlled for a while and then become more complex, and some affected individuals experience intractable seizures that have never been controlled with medication.
Attention deficit disorder/hyperactivity has been reported in a number of children with dup15q syndrome.
Parent reports of anxiety disorders in children with dup15q syndrome have been noted on the Dup15q Alliance online community. More research in this area is needed.
Other reported medical problems include recurrent respiratory infections in childhood, middle ear effusions requiring tubes, eczema, precocious puberty, other menstrual irregularities, overeating, and weight gain. Scoliosis is also reported in adolescence.
At the present time there is no specific treatment that can undo the genetic pattern seen in people affected by chromosome 15q duplications. Although the fundamental genetic differences cannot be reversed, therapies are available to help address many of the symptoms associated with dup15q syndrome. Physical, occupational, and speech therapy along with special education techniques can stimulate children with dup15q syndrome to develop to their full potential.
In terms of medical management of the symptoms associated with dup15q syndrome, families should be aware that individuals with chromosome 15 duplications may tolerate medications differently and may be more sensitive to side effects for some classes of medications, such as the selective serotonin reuptake inhibitors (SSRIs). These medications should be used with caution and any new medication should be instituted in a controlled setting, with slow titration up to the expected therapeutic dose, and with a clear idea of the expected outcome for the treatment. This includes supplements.