What are the other Names for this Condition? (Also known as/Synonyms)

• 2q Duplication Syndrome
• Partial Trisomy 2q Syndrome
• Trisomy 2q Syndrome

What is Chromosome 2q Duplication Syndrome? (Definition/Background Information)

• Chromosome 2q Duplication Syndrome is a rare chromosome abnormality that occurs when there is an extra copy of genetic material on the long arm (q) of chromosome 2. The severity of the condition and the signs and symptoms depend on the size and location of the duplication and which genes are involved. The condition affects newborn children (congenital manifestation); If large segments of the chromosome are missing, then the child may have severe abnormalities
• It can result in developmental delays, poor motor skills, heart and brain abnormalities, seizures, and vision and hearing impairment. Chromosome 2q Duplication Syndrome may present complications such as malnutrition due to feeding difficulties, delayed achievement of milestones, abnormal spinal curvature, and reduced quality of life
• This chromosomal anomaly may develop from sporadic mutations (vast majority of cases), or it may be inherited from one’s parents (very rarely). 2q Duplication Syndrome may be diagnosed through specialized genetic testing. In some children, the condition may be mild and hence can also remain undiagnosed
• Following a diagnosis, the condition may be managed based on the presenting symptoms and extent of involvement of the body systems. The treatment may involve physician experts from several specialties, and can include the use of vision and hearing aids, seizure control, speech and language therapy, physiotherapy, and surgery for correction of physical defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 2q Duplication Syndrome are able to cope well through adequate treatment and supportive care. Some of the signs and symptoms associated with the condition are known to improve with time

Who gets Chromosome 2q Duplication Syndrome? (Age and Sex Distribution)

• Chromosome 2q Duplication Syndrome is a rare congenital disorder. The presentation of symptoms may occur at or following the birth of the child
• In many cases, individuals with mild signs and symptoms may be undiagnosed in their lifetime. Hence, a true incidence of the disorder may be difficult to estimate
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Chromosome 2q Duplication Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 2q Duplication Syndrome.

• In some individuals, a positive family history may be an important risk factor for 2q Duplication Syndrome
• Currently, no environmental and lifestyle (including dietary) factors have been implicated
• The syndrome is not caused by what the expectant mother does or does not do, either prior to or during pregnancy

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Chromosome 2q Duplication Syndrome? (Etiology)

• Chromosome 2q Duplication Syndrome may be caused by:
  • De-novo duplication of genetic material in the long arm (q) of chromosome 2 (most common cause)
  • Inheritance of duplicated genetic material in the long arm of chromosome 2 (in rare cases)
• The amount of chromosome material added/duplicated varies widely from one individual to another resulting in a variable set of signs and symptoms
  • The genes involved may include - MYT1L, SOX11, MYCN, and Gdf7 genes
  • Balanced and unbalanced reciprocal translocations and inverted duplication of 2p (with deletion of genetic material) has also been observed

It is important to note that a child’s development and future is not only influenced by the chromosome material duplicated/deleted and genes involved, but also by other factors such as one’s environment, involvement of other genes, and unique personality

Additional (general) information on chromosomes, which is helpful in understanding the disorder:

Chromosomes are microscopic thread-like protein structures present in each cell nucleus that carry genetic information in the form of DNA (deoxyribonucleic acid). DNAs are nucleic acids that encodes the genetic information of any organisms; a basic unit of the DNA is termed a gene with a specific set of instructions and a defined function. Each chromosome is “X” shaped with a center, called the centromere, and two short arms (termed p arms) and two long arms (termed q arms).

Humans have 46 chromosomes in the cell nucleus, in 23 pairs, of which one pair is named the sex chromosome. In males, it is designated XY, for chromosome X and chromosome Y; while, in females, it is designated XX, for a pair of chromosome X. The other 22 pairs of chromosomes are numbered chromosome 1 through 22, approximately according to size (with chromosome 1 being the largest; chromosome 21 being the smallest) and are referred to as autosomes or somatic chromosomes. During conception, the embryo inherits one copy of each chromosome from each parent (i.e., mother and father). Any alteration in the chromosome numbers or structure, such as via addition or deletion of chromosomal material, can result in mild to severe genetic abnormalities that may manifest as birth defects, growth delays, and intellectual disabilities.

A chromosome duplication disorder indicates that a certain portion of the chromosomal material is duplicated, which may be detected through molecular genetic testing. Depending on the nature and amount of extra material, the manifestation of a set of signs and symptoms are noted.

What are the Signs and Symptoms of Chromosome 2q Duplication Syndrome?

The signs and symptoms of Chromosome 2q Duplication Syndrome may be significantly different from one individual to another. The degree of signs and symptoms are often related to the amount of chromosome material added and the number of genes affected. As a general rule, a small gain in chromosome material generally results in milder signs and symptoms. Conversely, larger gains/duplications of the chromosome material generally results in severe signs and symptoms. It is important to note that exceptions may also occur, where individuals with small amount of chromosomal gains, may have disproportionately severe presentations.

The associated signs and symptoms depend on what material is duplicated, how much duplication has occurred (quantity), where the duplications occurs (such as at the tip or center of the chromosome), and if the involvement of another chromosome is noted (known to occur in some cases).

The commonly noted signs and symptoms of Chromosome 2q Duplication Syndrome include:

• Poor muscle tone (hypotonia) causing motor delays that can be mild or severe
• Feeding problems (sucking and swallowing) leading to small and underweight children
• Developmental delays; short stature
• Abnormal facial features that may include prominent forehead, widely-spaced eyes, large nose bridge, abnormally-placed ears, and small lips and mouth
• Cleft palate
• Hands and feet deformities
• Vision defects that include strabismus, absence of tear ducts, shortsightedness and longsightedness, and refractory errors
• Breathing issues in some of the children (mostly sleep apnea)
• Hearing impairment, mostly due to glue ear (fluid buildup in the middle ear)
• Dental abnormalities such as misalignment of teeth, small teeth, or late eruption of permanent teeth
• Heart abnormalities may be observed that can result in associated signs and symptoms, such as chest pain, shortness of breath, dizziness, fainting, palpitations, and tiredness, among others. The type of heart defects include atrial septal defect (ASD), ventricular septal defect (VSD), and coarctation of the aorta
• Intellectual disability
• Sleep disturbances that can affect one’s physical and mental health
• Behavioral problems that may include aggressiveness, mood swings, and frustration, which are usually temporary
• Speech and language delays
• Seizures in some children and adults
• Congenital diaphragmatic hernia
• Intestinal anomalies may include Meckel’s diverticulum and intestinal malrotation
• Eczema causing dry skin

How is Chromosome 2q Duplication Syndrome Diagnosed?

Children can have varying signs and symptoms. Some children with mild signs and symptoms may go undiagnosed in their lifetimes. Given the rarity of the condition, the healthcare provider should have a high index of suspicion to consider Chromosome 2q Duplication Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 2q Duplication Syndrome is diagnosed on the basis of the following information:

• Complete physical examination and thorough medical history evaluation, including family medical history
• Assessment of the presenting signs and symptoms, including evaluation of body systems such as vision, hearing, muscles, heart, kidneys, central nervous system, genitalia, and immune system
• Hearing assessment through various tests including:
  • Otoscopy: Examination using an instrument that allows the physician to look inside the ear
  • Weber test: A test in which a vibrating tuning fork is placed on the midline of the head
  • Rinne test: A test in which a vibrating tuning fork is held next to the ear and then in front of the ear, until the individual no longer hears the sound
  • Audiometric test: Hearing tests that involve listening to different tones
  • Tympanometry: A test that puts air pressure in the ear canal in order to move the eardrum, and then measures the eardrum mobility (movement)
• Eye and vision assessment through:
  • General eye exam
  • Visual acuity test using a special and standardized test chart (Snellen chart)
  • Refraction studies using various instruments
  • Alignment and focusing testing
  • Fundoscopic (ophthalmoscopic) examination by an eye specialist, who examines the back part of the eye (or the fundus)
  • Slit-lamp examination
  • Visual evoked potential (VEP) test
  • Fundus fluorescein angiography
  • Optical coherence tomography (OCT) of eye
• Evaluation of heart defects through:
  • Chest X-rays
  • Echocardiogram
  • Electrocardiogram (EKG)
  • Cardiac catheterization
  • Fetal ultrasound for heart defects
• Laboratory tests, as needed, such as electrolyte levels, serum calcium levels, thyroid function test, kidney function test, urine tests, sex hormone studies, etc.
• Radiological studies of the affected regions, as needed
• Brain scans (to determine corpus callosum): These may include prenatal ultrasounds and MRI scans, and CT/MRI scans after development of the child
• Neurological examination that involves the central nervous system (brain and spinal cord)
• Behavioral studies
• Prenatal studies including abdominal ultrasonography
• Specialized genetic testing techniques are often required to confirm the diagnosis. This may include:
  • Fluorescence in situ hybridization (FISH) testing
  • Array comparative genomic hybridization (array-CGH)
  • DNA sequencing

Often, karyotyping of the chromosome is not adequate to diagnose the condition, since individuals with this condition can have normal karyotype chromosomal studies.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Chromosome 2q Duplication Syndrome?

The potential complications of Chromosome 2q Duplication Syndrome may include the following:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR); some babies are underweight at birth
• Delayed milestone achievement; rolling, sitting, and walking in children may be delayed
• Poor growth due to malnutrition caused by weak suckling
• Abnormal development of lungs in some children
• Frequent respiratory infections
• Spinal curve abnormalities, such as scoliosis, which mostly develops from hypotonia; this may be mild or severe
• Retinal detachment and other severe eye abnormalities causing vision loss
• Severe intellectual deficiency
• Inappropriate or violent behavior
• Kidney and urinary tract defects
• Physical abnormalities that can cause difficulties in day-to-day living
• Reduced quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Chromosome 2q Duplication Syndrome Treated?

There is no cure for Chromosome 2q Duplication Syndrome since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. It also depends on the severity of the signs and symptoms and the body systems affected. Individuals with mild signs and symptoms may require periodic monitoring without significant medical intervention. Often, a multidisciplinary team of specialists including pediatricians, ophthalmologists, otolaryngologists, neurologists, internists, cardiologists, endocrinologists, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for Chromosome 2q Duplication Syndrome may involve:

• Use of hearing aids; in case of fluid buildup in the middle ear, some children may require the placement of a small ventilation tubes to help with improved fluid drainage
• Seizure control using anticonvulsant medication, vitamin supplements, and ketogenic diet: Seizure control is important to ensure that the child’s learning ability is not significantly affected
• Employing suitable learning strategies via music therapy, visual and tactile books, learning through fun and play, and lots of repetition. Writing by holding a pencil may be very difficult; but touchscreen computers and keyboards are known to be easier to use and learn
• Speech and language therapy; the use of sign language may be beneficial; rectification of hearing impairment may improve speech and language development
• Physiotherapy for weakened muscles, including incorporating daily exercise regimen
• Development of motor skills via daily exercises, swimming, hydrotherapy, and other adapted activities; use of specially-designed toys and daily-used items (such as spoons and cups)
• For feeding difficulties, use of feeding tubes (temporary nasogastric or gastrostomy tubes), medications, feed thickeners, bottle-feeding expressed milk, including special diets and nutritional supplements
• Heart abnormalities may require surgical correction in some cases; some defects, such as patent ductus arteriosus, tend to improve over time without any invasive procedures
• Surgical correction of physical defects, as assessed by a healthcare expert
• Use of padded brace for abnormal spinal curvature and posture management, including surgical correction of severe cases. Also, children may be provided specially designed furniture, such as chairs, tables, and beds, for spine support while sitting and sleeping
• Pavlik harness may be used for children with congenital hip dislocation; in some, surgery may be needed to reposition the hip, followed by the use of padded braces
• Use of suitable glasses and surgical rectification of vision defects, if necessary
• Sleep disorders may require medication; daytime naps may be advised
• For eczema, the treatment may involve the use of moisturizing creams and emollients and steroid creams as necessary; many children overcome the condition as they get older
• Hernia repair surgery for inguinal hernias, as needed
• Psychotherapy, behavior modification, and establishing discipline techniques, as necessary
• Occupational therapy

Regular medical screening at periodic intervals with tests and physical examinations are necessary and highly recommended.

How can Chromosome 2q Duplication Syndrome be Prevented?

Chromosome 2q Duplication Syndrome may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child. A majority of cases are sporadic occurrences, which means there is no family history of the condition.

In some rare cases, the condition may be familial, meaning they occur within families. In expecting parents with a familial history:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

It is important to note that the chances of both the parents with normal chromosomes having another child with Chromosome 2q Duplication Syndrome is highly unlikely. This may be confirmed via specialized prenatal testing and preimplantation genetic diagnosis (PGD), if needed. Prenatal tests may include chorionic villus sampling (CVS) and amniocentesis.

What is the Prognosis of Chromosome 2q Duplication Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 2q Duplication Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any noted. It may be assessed on a case-by-case basis, but it is generally difficult to predict the long-term outlook.

• Children with mild conditions are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Children usually require lifelong medical support and care; those with severe organ involvement, such as the heart, brain, or kidneys, may have unfavorable prognosis

Additional and Relevant Useful Information for Chromosome 2q Duplication Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/