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

• 22q Duplication Syndrome
• Partial Trisomy 22q Syndrome
• Trisomy 22q Syndrome

What is Chromosome 22q Duplication Syndrome? (Definition/Background Information)

• Chromosome 22q Duplication Syndrome is a genetic disorder manifested at birth, with wide-ranging but highly variable signs and symptoms depending on the specific nature of the chromosomal abnormality (size and location of duplication) and the number of genes affected, and the function of the affected genes
• Chromosome 22q Duplication Syndrome is characterized by the presence of additional copy (either full or partial) of genetic material on the long arm (q) of chromosome 22 in the cells. This results in associated signs and symptoms that include abnormal facial features, hearing loss, cardiac abnormalities, mental health issues, and growth delays
• This chromosomal anomaly may develop from sporadic mutations (majority of cases), or it may be inherited from one’s parents (very rarely). Duplication 22q Syndrome may be diagnosed through specialized genetic testing. Following a diagnosis, the condition may be managed based on the presenting symptoms and extent of involvement of multiple body systems
• The management of Chromosome 22q Duplication Syndrome may involve physician experts from multiple specialties including pediatrics, cardiology, child neurology, otolaryngology, and rehabilitation medicine. The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Some of the signs and symptoms associated with the condition are known to improve with time

Who gets Chromosome 22q Duplication Syndrome? (Age and Sex Distribution)

• According to medical literature, the incidence of Chromosome 22q Duplication Syndrome is around 1 in 1,140 among the general population
• Chromosome 22q Duplication Syndrome is a rare and sometimes undiagnosed congenital disorder; per experts, the true incidence may not be known
• The symptoms of this genetic disorder may be observed at birth and as the child grows
• 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 22q Duplication Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 22q Duplication Syndrome.

• A positive family history may be an important risk factor, since 22q Duplication Syndrome can be inherited
• 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 22q Duplication Syndrome? (Etiology)

Chromosome 22q Duplication Syndrome may be caused by:

• A de novo duplication of genetic material in the long arm (q) of chromosome 22, which may be observed in about one-third of the cases. Thus, when it occurs as a random (de novo) mutation, both parents do not demonstrate genetic abnormalities
• Heritable changes passed from a parent with 22q Duplication Syndrome in which a subsequent chromosomal re-arrangement has led to a balanced translocation 
• If the chromosomal re-arrangement does not result in a net gain or loss of genetic material, it is known as a “balanced translocation”
• Those with balanced translocation of 22q can have abnormalities in the development of egg or sperm, causing the disorder in the offspring
• Over two-thirds of the cases are inherited from duplication of chromosome 22q present in one of the parents. If a parent has the chromosomal abnormality, the child has a 50% probability of getting the disorder
• It is observed that when the duplication of material occurs at the tip of the chromosome, the conditions are generally mild. In severe cases, where large duplications are noted (or the centromere is involved), the child may be severely affected. The extra chromosome in Chromosome 22q Duplication Syndrome may contain at least 40 extra genes

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 22q Duplication Syndrome?

The signs and symptoms of Chromosome 22q Duplication Syndrome may be determined by the size and the genes present in the of duplicated genetic material. The syndrome can affect a variety of body systems resulting in a wide array of signs and symptoms, which may vary from one individual to another. It is also observed that some individuals may have no intellectual or physical findings despite having duplication of 22q, thus making it challenging to recognize or detect the disorder.

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 potential signs and symptoms of Chromosome 22q Duplication Syndrome include:

• Distinctive facial features such as:
  • Small or large-sized head and narrow face
  • High forehead
  • Cleft palate
  • Flat and broad nose
  • Widely set eyes
  • Abnormal eye folds and downward slanting of eyelid openings
  • Creased earlobes
  • Low-set ears with abnormal ear profile
  • Small-sized jaw
• Poor muscle tone
• Feeding difficulties
• Hearing impairment
• Underdeveloped heart; heart valve defects
• Seizures and balance issues
• Narrow urethral opening and excess urine accumulation in the kidneys and ureters
• Global developmental delay
• Delay in speech and language development
• Intellectual disability
• Behavioral problems such as anxiety and obsessive compulsive behavior

How is Chromosome 22q 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 22q Duplication Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

22q Duplication Syndrome is diagnosed on the basis of the following information, as determined by the healthcare provider:

• 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 the heart, kidneys and urinary bladder system, endocrine system, brain and spinal cord, immune system, etc.
• Hearing and vision assessment
• Assessment of cardiac function
• 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
• Neurological examination that involves the central nervous system (brain and spinal cord)
• Behavioral studies
• Prenatal studies including abdominal ultrasonography

The diagnosis of Chromosome 22q Duplication Syndrome often requires specialized genetic testing; karyotyping does not usually help in detecting the syndrome. It is often diagnosed using any of the special genetic techniques such as:

• Array genomic hybridization (array GH) testing
• Multiplex ligation-dependent probe amplification (MLPA) testing

The above genetic tests can be performed on the following samples:

• Peripheral blood
• Analysis of placental tissues (after birth)
• Analysis of amniotic fluid, called amniocentesis, during pregnancy
• Also, chorionic villus sampling (CVS) may be performed during pregnancy

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 22q Duplication Syndrome?

The complications of Chromosome 22q Duplication Syndrome may vary from one child to another and may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Failure to thrive
• Velopharyngeal insufficiency (VPI) - observed in a large percentage of the cases, especially in children with cleft palate
• Total deafness
• Attention deficit hyperactivity disorder (ADHD) and autism
• Immune dysfunction causing frequent respiratory infections
• Thyroid gland abnormalities
• Tetralogy of Fallot (heart abnormality)
• Scoliosis or abnormally curved spine
• Severe growth delays and physical developmental issues, including short stature; difficulty in achieving growth milestones
• Learning disabilities
• Severe intellectual deficiency
• Inappropriate or violent behavior
• Physical abnormalities that can cause difficulties in day-to-day living
• Decreased quality of life

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

How is Chromosome 22q Duplication Syndrome Treated?

There is no cure for Chromosome 22q 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. Often, a multidisciplinary team of specialists including pediatricians, neurologists, behavioral study experts, internists, cardiologists, urologists, endocrinologists, otolaryngologists, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for 22q Duplication Syndrome may involve:

• Antiseizure medication and vagus nerve stimulation for seizure disorders, as evaluated by the healthcare expert
• Employing suitable learning strategies via music therapy, visual and tactile books, touch screen computers, etc.
• Speech and language therapy; the use of sign language may be beneficial
• Physiotherapy for stiff muscles, including incorporating daily exercise regimen
• Development of motor skills via daily exercises, swimming, and other adapted activities
• For feeding difficulties, use of feeding tubes (temporary), medications, feed thickeners, including special diets and nutritional supplements
• Medications to control anxiety, depression, and obsessive-compulsive behavior
• Administration of medications and correction of heart defects
• Use of hearing aids, cochlear implants, and speech-language therapy
• Thyroid hormone therapy, as required
• Nutritional support, including calcium supplementation and growth hormone therapy
• Surgical correction of physical defects, as assessed by a healthcare expert, such as surgical repair of cleft lip
• Use of padded brace for abnormal spinal curvature, including surgical correction for severe cases
• Physical therapy, occupational therapy, and supportive care
• Psychotherapy, behavior modification, and family therapy
• Social skills training support groups

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

How can Chromosome 22q Duplication Syndrome be Prevented?

Chromosome 22q 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 1p 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 22q Duplication Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 22q Duplication Syndrome is primarily dependent upon the severity of the signs and symptoms and associated complications.

• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• A healthy functional life may be expected in children with mild conditions presenting minimal complications and mild-moderate growth issues. In such cases, the outcomes are typically good to excellent
• Some children may present poor growth, severe heart abnormalities, and cognitive impairment, requiring constant medical intervention and support. In such cases, the prognosis may be guarded
• It may also take some children a long time (often several years) to gain a measure of independence

Additional and Relevant Useful Information for Chromosome 22q Duplication Syndrome:

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

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