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

• Mosaic Trisomy Chromosome 22 Syndrome
• Trisomy 22 Mosaicism

What is Mosaic Trisomy 22 Syndrome? (Definition/Background Information)

• Mosaic Trisomy 22 Syndrome is a rare chromosomal disorder in which there are 3 copies (trisomy) of chromosome 22 in some cells of the body, while other cells have the usual two copies. The extent and severity of features in affected individuals can vary from one to another
• The signs and symptoms of Mosaic Trisomy 22 Syndrome that have been most commonly reported include growth and developmental delays, poor intellectual abilities, unequal development of the body, presence of several pigmented moles, craniofacial malformations, and other physical deformities
• This condition is most often caused by an error in cell division in the egg or sperm cell before conception, or in fetal cells after fertilization. Presently, no inherited cases of the condition is reported. Following a diagnosis, Mosaic Trisomy 22 Syndrome 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 Mosaic Trisomy 22 Syndrome are able to cope well through adequate treatment and supportive care. Some of the abnormalities are also known to improve with time

Who gets Mosaic Trisomy 22 Syndrome? (Age and Sex Distribution)

• Mosaic Trisomy 22 Syndrome is a rare chromosomal disorder. Its exact prevalence is not known, but fewer than 20 cases are reported in the medical literature
• The onset of symptoms may occur at or following birth
• 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
• The condition can affect both genders. However, the disorder is more prevalent in females

What are the Risk Factors for Mosaic Trisomy 22 Syndrome? (Predisposing Factors)

• Currently, no risk factors have been clearly identified for Mosaic Trisomy 22 Syndrome
• Also, 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 Mosaic Trisomy 22 Syndrome? (Etiology)

• Mosaic Trisomy 22 Syndrome may be caused by an abnormal cell division (called nondisjunction) during the development of egg or sperm
• This abnormal cell division leads to an extra chromosome 22 in some cells
• If an egg or sperm cell with three copies of chromosome 22 fuse resulting in an embryo, this embryo will have 3 copies of chromosome 22 in each cell
• A process known as “trisomy rescue” may occur to eliminate the extra chromosome from embryonal cells. This process may not be completely successful, leaving some cells with a normal set of chromosomes, and others with an extra chromosome
• Trisomy 22 Mosaicism may also be caused by abnormal cell division in a fertilized egg (very early stages of embryo development), resulting in an extra chromosome 22 in some cells
• The percentage of cells with the extra chromosome 22 may vary among affected individuals and may determine the severity of signs and symptoms
• Almost all cases of the disorder are known to occur sporadically (de novo occurrence); a positive family history is not yet reported

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.

What are the Signs and Symptoms of Mosaic Trisomy 22 Syndrome?

The signs and symptoms of Mosaic Trisomy 22 Syndrome may vary among affected individuals and may be determined by the number of cells that carry an extra copy of chromosome 22. The signs and symptoms may include:

• Delayed growth 
• Body asymmetry due to unequal development (hemi dystrophy) 
• Pigmented moles and/or birthmarks
• Poor or abnormal nail development 
• Facial malformation including:
• Drooping eyelids
• Widely spaced eyes
• Epicanthal folds
• Pits in front of ears
• Toe and finger abnormalities
• Webbed neck
• A low hairline at the back of neck
• Unilateral hearing impairment
• Abnormal elbow deviation when extended (cubitus valgus)
• Intellectual deficiency
• Cognitive deficiencies
• Malformed kidneys
• Structural and functional abnormalities of the heart
• In girls, underdeveloped ovaries
• Delayed puberty
• Delayed development of secondary sexual growth

How is Mosaic Trisomy 22 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 Mosaic Trisomy 22 Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Mosaic Trisomy 22 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 and vision assessment
• Evaluation of 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: In some cases, a pregnancy ultrasound may reveal signs and symptoms that are suggestive of a chromosomal or developmental disorder. Following this, additional tests may be conducted, including:
  • Chorionic villus sampling (CVS)
  • Amniocentesis
• 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 Mosaic Trisomy 22 Syndrome?

The complications of Mosaic Trisomy 22 Syndrome may include:

• Severe emotional stress for parents and caregivers
• Failure to thrive
• Delayed milestone achievement
• Severe intellectual deficiency
• Infertility
• Kidney malfunction
• Cardiomyopathy
• Social ostracism
• Reduced quality of life

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

How is Mosaic Trisomy 22 Syndrome Treated?

There is no cure for Mosaic Trisomy 22 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 Mosaic Trisomy 22 Syndrome may involve:

• Use of hearing aids, if required
• 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
• Special education: Employing 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)
• Use of walking aids including foot orthotics and special footwear and shoe inserts; wheelchair assistance may be necessary
• 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 may improve over time without any invasive procedures
• Surgical correction of physical defects, as assessed by a healthcare expert
• Use of suitable glasses and surgical rectification of vision defects, if necessary
• 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 Mosaic Trisomy 22 Syndrome be Prevented?

• Mosaic Trisomy 22 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
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Mosaic Trisomy 22 Syndrome? (Outcomes/Resolutions)

The prognosis of Mosaic Trisomy 22 Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any.

• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Many children are known to require extended medical support and care

Additional and Relevant Useful Information for Mosaic Trisomy 22 Syndrome:

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

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