Signs, Symptoms and Characteristics

PHYSICAL FEATURES

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:

Hypotonia

Babies with dup15q usually have hypotonia (poor muscle tone). They may appear "floppy" and have difficulty sucking and feeding. 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.

Facial Features

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.

Traditional medical photographic images of people with chromosome disorders are sadly negative — with little opportunity to celebrate the beauty and diversity of affected individuals. On this page Dup15q Alliance presents images of individuals with chromosome 15q11.2-13.1 duplication (dup15q) syndrome. Through these images, we hope that you will gain an appreciation for the subtle physical characteristics in this disorder, along with the beauty and joy in each child.

Nose

Many children with Dup15q share similar facial characteristics. These include a flat nasal bridge which gives them a "button" nose.

Eyes

There may be skin folds, called "epicanthi" or epicanthal folds, at the inner corners of the eyes, and the eyes may be deep set.

Ears

Ears may be low-set and/or posteriorly rotated. There may also be noticeable unfolding of the edge of the ears.

Skin Pigmentation

Affected individuals may have increased or reduced skin pigmentation, as seen on the backs of the legs in the picture below.

Growth

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.

Other Physical Changes

Rarely, babies with dup15q 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 to be carefully evaluated for the possibility of such structural differences. Hypogonadism (including undescended testicles) is reported in about 20% of affected individuals. Although puberty is reportedly normal in most individuals, pubertal disorders such as central precocious puberty have been observed in girls. A complete genitourinary exam is recommended for children diagnosed with dup15q.  Check with your genetics specialist for specific recommendations.

DEVELOPMENTAL

Gross Motor

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 although some degree of ataxia (coordination problems) may be apparent.

Fine Motor

Parent report suggests 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.

Cognitive

 Most individuals with dup15q syndrome show some degree of cognitive delay/disability/learning disabilities, including intellectual disability at the more involved end of the spectrumfrom very early on. These cognitive disabilities are often associated with behavioral problems as children age.

Speech/Language

Most children with dup15q 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, 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 44.1m (range 9-114 months). While the majority of children with dup15q experience speech delays, a small subset of children are highly verbal.

Behavior

Many children with dup15q 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.

Autism Spectrum Disorders

Although not all children with duplications develop autism the majority will likely meet clinical criteria for an Autism Spectrum Disorder.  Two studies that included a total of 226 patients with autism found dup15q in approximately 3-5% of the patients. Chromosome 15q11-13 duplications are the most frequently identified chromosomal cause in individuals with autism.  

Sensory Processing Disorders

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.

Attention Deficit Disorders

Attention deficit disorder/hyperactivity has been reported in a number of children with dup15q syndrome.

Anxiety Disorders

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.

MEDICAL

Seizure Disorders

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. The prevalence of infantile spasms among a surveyed group of families was unusually high and suggests that idic(15) could account for a significant percentage of infants experiencing those episodes. Infantile spasms associated with an hypsarrhythmic (disorganized) EEG have been reported in the scientific literature. Typical Lennox-Gastaut syndrome or Lennox-Gastaut-like syndrome was observed in the four patients with idic(15) reported by Battaglia et al. These had tonic/atonic (head drops or drop attacks), tonic-clonic seizures and atypical absences with onset between 4 and 8 years of age. Complex partial and myoclonic seizures have been observed in a number of other affected individuals.   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.There are many reports in the scientific literature and from parents of seizures that are difficult to control, despite adequate antiepileptic treatment. Difficult to control seizures associated with some degree of deterioration have also been reported.

INCREASED RISK FOR SUDDEN DEATH

There is an increased risk of sudden, unexpected and currently unexplained death among children and young adults ages 7 and older with chromosome 15q11.2-13.1 duplication syndrome. The risk is small, estimated at 0.5-1% per person per year. Physicians should be alert for potentially relevant symptoms and follow up their patients according to their best clinical judgment. Benzodiazepines and barbiturates should only be used if alternatives are not available, given a possible association with sudden death in this chromosomal disorder. For more information, see the Physician Advisory Sudden Death in Chromosome 15q Duplication Syndrome.

Other Medical Problems

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.