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

• Mosaic Trisomy 8 Syndrome
• T8M (Trisomy 8 Mosaicism)
• Warkany Syndrome

What is Trisomy 8 Mosaicism? (Definition/Background Information)

• Trisomy 8 Mosaicism (T8M) 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 8 (trisomy), while other cells have the usual two copies of this chromosome. The condition is predominantly observed in boys
• 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; Trisomy 8 Mosaicism often occurs sporadically as a random event during the formation of the reproductive cells (egg and sperm) or as the fertilized egg divides. Following a diagnosis, the condition may be managed based on the presenting symptoms and extent of involvement of the body systems
• The treatment of Trisomy 8 Mosaicism may involve physician experts from several specialties, and can include the speech and language therapy, physiotherapy, seizure control, and surgery for correction of heart defects and other defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Trisomy 8 Mosaicism 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 Trisomy 8 Mosaicism? (Age and Sex Distribution)

• Trisomy 8 Mosaicism is a rare congenital disorder. The condition affects 1 in every 25,000 to 50,000 infants
• 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; but a majority of the affected children are boys (boy-girl ratio is 4:1)
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Trisomy 8 Mosaicism? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Trisomy 8 Mosaicism (T8M).

• A positive family history may be an important risk factor, since T8M can be rarely 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 also not associated with the age of the parents at conception

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 Trisomy 8 Mosaicism? (Etiology)

• Individuals with Trisomy 8 Mosaicism have a duplication of chromosome 8 material in some of their cells, while other cells have a normal chromosomal makeup. The additional chromosomal material is responsible for the features that are characteristic of the condition
• Most cases of Trisomy 8 Mosaicism appear to result from random errors in the separation of chromosomes (termed nondisjunction), either during the division of the egg or sperm in one of the parents, or during cell division after fertilization

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 Trisomy 8 Mosaicism?

The signs and symptoms of Trisomy 8 Mosaicism 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:

• Children may have a short neck (with extra skin folds), a long slender body, with a narrow chest, shoulders, and pelvis, that may get more prominent with age
• Abnormal facial features such as:
  • Widely-spaced eyes
  • Bulbous nose with upturned nostrils
  • Protruding lower lip
  • Large ears
  • Small jaw
  • Protruding lower lip
• Abnormalities involving the limbs including:
  • Stiff joints having a limited movement range
  • Bent fingers and/or toes
  • Deep creases on the palms and soles
  • Underdeveloped nails (occasionally)
  • Missing or small kneecaps
• Motor skills difficulties
• Feeding difficulties, including chewing and swallowing difficulties; many babies are observed with tongue ties that makes it difficult for them to suckle
• Kidney and urinary anomalies may be observed in nearly 50% of the cases
• Congenital heart conditions are noted in nearly 25% of the cases. Heart abnormalities can result in associated signs and symptoms, such as chest pain, shortness of breath, dizziness, fainting, palpitations, and tiredness, among others
• Brain abnormalities such as corpus callosum (underdeveloped band of nerve fibers linking the two brain hemispheres)
• Fused bones in the spine
• Mild to moderate intellectual disabilities
• Speech and communication delays; learning difficulties
• Seizures are noted in nearly 16% of the affected children
• Minor genital defects, especially in boys
• Behavioral issues may include mood swings, self-injurious tendency, and rarely, violent and aggressive behavior
• Delayed puberty
• Hearing impairment from glue ear and conductive deafness (that is usually temporary)
• Vision impairment from strabismus, cataracts, and coloboma
• Sleep disturbances

How is Trisomy 8 Mosaicism 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 Trisomy 8 Mosaicism in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Trisomy 8 Mosaicism 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 alpha feto-protein (AFP) blood test in pregnancy and abdominal ultrasonography. In some cases, Trisomy 8 Mosaicism 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 Trisomy 8 Mosaicism?

The complications of Trisomy 8 Mosaicism may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications, including preterm birth
• Intrauterine growth retardation (IUGR); some babies are underweight at birth
• Failure to thrive
• Delayed milestone achievement
• Some children may be unable to walk without proper supports
• Increased risk for fall injuries from sudden seizure attacks
• Frequent infections due to poor immunity
• Recurrent middle ear infections from a condition known as velopharyngeal insufficiency (VPI)
• Irreversible vision loss
• Autism spectrum disorders, including attention-deficit hyperactivity disorder (ADHD)
• Abnormal curvature of the spine (scoliosis)
• Severe heart abnormalities
• Dysfunction of the kidneys
• Severe abnormalities due to brain malformation
• Some individuals are at a slight risk for developing leukemia or other malignancies
• Infertility, especially in men
• Reduced quality of life

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

How is Trisomy 8 Mosaicism Treated?

There is no cure for Trisomy 8 Mosaicism 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 Trisomy 8 Mosaicism may involve:

• 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 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
• Use of suitable glasses and rectification of vision defects
• 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
• 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 Trisomy 8 Mosaicism be Prevented?

Trisomy 8 Mosaicism 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.

• 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 Trisomy 8 Mosaicism 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 Trisomy 8 Mosaicism? (Outcomes/ Resolutions)

The long-term outlook for individuals with Trisomy 8 Mosaicism varies and largely depends on the severity and range of signs and symptoms present.

• An early diagnosis and appropriate treatment can improve the quality of life of the affected individuals
• Some of the abnormalities are known to resolve or improve with time
• Many children require lifelong medical support and care

Additional and Relevant Useful Information for Trisomy 8 Mosaicism:

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

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