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

• Mosaic Trisomy Chromosome 9
• Trisomy 9 Mosaicism

What is Mosaic Trisomy 9 Syndrome? (Definition/Background Information)

• Mosaic Trisomy 9 Syndrome is a chromosomal abnormality that can affect may parts of the body. In individuals affected by this condition, some of the body's cells have three copies of chromosome 9 (trisomy), while other cells have the usual two copies of this chromosome
• The signs and symptoms vary but may include mild to severe intellectual disability, developmental delay, growth problems (both before and after birth), congenital heart defects, and/or abnormalities of the craniofacial (skull and face) region
• Most cases are not inherited; Mosaic Trisomy 9 Syndrome often occurs sporadically as a random event during the formation of the reproductive cells (egg and sperm) or as the fertilized egg divides

(Source: Mosaic Trisomy 9; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

• 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 heart 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 9 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 9 Syndrome? (Age and Sex Distribution)

• Mosaic Trisomy 9 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 Mosaic Trisomy 9 Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Mosaic Trisomy 9 Syndrome.

• A positive family history may be an important risk factor, since Trisomy 9 Mosaicism 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 Mosaic Trisomy 9 Syndrome? (Etiology)

Most cases of Mosaic Trisomy 9 Syndrome occur due to a random event during the formation of the reproductive cells (egg and sperm) or after fertilization has taken place.

• An error in cell division (called nondisjunction) may cause some eggs or sperm to have an abnormal number of chromosomes
• If an egg or sperm with an extra chromosome 9 contributes to the genetic makeup of an embryo, the embryo will have an extra copy of chromosome 9 in each cell
• As the embryo grows and divides, an attempt may be made to correct the mistake by eliminating one extra chromosome 9
• In individuals with Mosaic Trisomy 9 Syndrome, this attempt may be partly successful, leaving some cells with an extra chromosome 9 and some cells with the extra chromosome deleted (the usual chromosome number). This correction process is called trisomy rescue

In other cases, the egg and sperm may have a normal number of chromosomes, but an error of cell division (nondisjunction) occurs when the fertilized egg is growing and dividing.

• If an error occurs during one of the divisions, it can cause some cells to have an abnormal number of chromosomes. In those with Mosaic Trisomy 9 Syndrome, some of the body's cells have the usual two copies of chromosome 9, and other cells have three copies of this chromosome (trisomy)
• The percentage of cells with trisomy 9 and which parts of the body are affected vary from person to person. This leads to variability in the range and severity of symptoms

Mosaic Trisomy 9 Syndrome is usually not inherited. It often occurs sporadically as a random event during the formation of the reproductive cells (egg and sperm) or as the fertilized egg divides.

• In rare cases, Mosaic Trisomy 9 is inherited from a parent with a chromosomal rearrangement called a "pericentric inversion"
• This occurs when a segment of chromosome 9 has broken off in two places, swiveled round 180 degrees and reinserted itself into the chromosome
• If this rearrangement is considered "balanced," meaning the piece of chromosome is in a different order but no genetic material is gained or lost, it usually does not cause any symptoms or health problems
• This can be associated with an increased risk of having children with an abnormal number or chromosomes

(Source: Mosaic Trisomy 9; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

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 9 Syndrome?

The signs and symptoms of Mosaic Trisomy 9 Syndrome may vary among affected individuals in type and severity. The degree of signs and symptoms are often related to the amount of chromosome material involved and the number of genes affected. The signs and symptoms may include:

• Different degrees of developmental delay and intellectual disability
• Abnormal growth including low birth weight, failure to thrive, hypotonia (low muscle tone), and short stature
• Characteristic craniofacial features may include:
  • Microcephaly (unusually small head)
  • Sloping forehead with narrow temples
  • Broad nose with a bulbous tip and slit-like nostrils
  • Small jaw
  • Abnormally wide fontanelles at birth
  • Cleft lip and/or palate
  • Low-set abnormally shaped ears
  • Microphthalmia (unusually small eyes)
  • Short and upwardly slanting eyelid folds (palpebral fissures)
• Vision problems
• Congenital heart defects
• Abnormalities of the muscles and/or bones such as:
  • Congenital dislocation of the hips
  • Abnormal position and/or limited function of the joints
  • Underdevelopment of certain bones
  • Unusually formed feet, such as club foot or "rocker bottom" feet
• Abnormalities of the male reproductive system such as:
  • Undescended testes
  • Small penis
  • Abnormal placement of the urinary opening
• Kidney problems
• Brain malformations such as hydrocephalus and/or Dandy-Walker malformation

(Source: Mosaic Trisomy 9; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Mosaic Trisomy 9 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 9 Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Mosaic Trisomy 9 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, Mosaic Trisomy 9 Syndrome may be diagnosed before birth. 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 9 Syndrome?

The complications of Mosaic Trisomy 9 Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR); some babies are underweight at birth
• Failure to thrive
• Delayed milestone achievement
• Abnormal curvature of the spine
• Severe heart abnormalities
• Vision defects
• Dysfunction of the kidneys
• Severe abnormalities due to brain malformation
• Reduced quality of life

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

How is Mosaic Trisomy 9 Syndrome Treated?

There is no cure for Mosaic Trisomy 9 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 9 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
• 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, such as surgical repair of cleft lip
• 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
• Surgical correction (orchiopexy) of undescended testicles and other genital defects
• Surgical correction of kidney reflux via ureteral reimplantation procedure
• Sleep disorders may require medication; daytime naps may be advised
• 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 9 Syndrome be Prevented?

Mosaic Trisomy 9 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 Mosaic Trisomy 9 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 Mosaic Trisomy 9 Syndrome? (Outcomes/ Resolutions)

The prognosis of Mosaic Trisomy 9 Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any. 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
• Some of the abnormalities are known to resolve or improve with time. However, severe congenital defects with the involvement of vital organs, such as the heart, kidneys
• Most children usually require lifelong medical support and care

Additional and Relevant Useful Information for Mosaic Trisomy 9 Syndrome:

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

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