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

• Chromosome 17 Duplication Syndrome
• Chromosome 17 Trisomy Syndrome
• Trisomy 17 Syndrome

What is Trisomy 17 Mosaicism? (Definition/Background Information)

• Trisomy 17 Mosaicism is an extremely uncommon chromosomal abnormality that is characterized by three copies of chromosome 17 against the usually two copies, in some of the body cells. The disorder occurs sporadically as a random event during the formation of the reproductive cells (egg and sperm) or as the fertilized egg divides
• When “all” the cells of the body present three copies of chromosome 17, it is termed as full trisomy 17. According to medical records, a full trisomy 17 is not yet described in individuals. Only a few cases of Trisomy 17 Mosaicism after birth have been confirmed
• The severity of signs and symptoms of Trisomy 17 Mosaicism can vary significantly from one individual to another, since it is dependent upon the proportion of cells with trisomy 17 (i.e., degree of mosaicism). This may include developmental delays, growth problems (both before and after birth), congenital heart defects, abnormalities of the craniofacial (skull and face) region, and brain anomalies
• The treatment measures for Trisomy 17 Mosaicism may involve physician experts from several specialties, and may include the use of hearing aids, speech and language therapy, physiotherapy, and surgery for correction of heart and other physical defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Children with Trisomy 17 Mosaicism are able to cope well through adequate treatment and supportive care

Who gets Trisomy 17 Mosaicism? (Age and Sex Distribution)

• Trisomy 17 Mosaicism is an exceedingly 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 are affected
• Individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Trisomy 17 Mosaicism? (Predisposing Factors)

Currently, no risk factors have been clearly identified for Trisomy 17 Mosaicism.

• 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 Trisomy 17 Mosaicism? (Etiology)

Trisomy 17 Mosaicism develops 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 (in this case, chromosome 17) in some cells
• If an egg or sperm cell with three copies of chromosome 17 fuse resulting in an embryo, this embryo may have 3 copies of chromosome 17 in “some” of the cells (no cases of full trisomy 17 is recorded, where “all” cells present an extra copy of chromosome 17)
• 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 17 Mosaicism may also be caused by abnormal cell division in a fertilized egg (very early stages of embryo development), resulting in an extra chromosome 17 in some cells
• The percentage of cells with the extra chromosome 17 may vary among affected individuals, and may determine the severity of signs and symptoms

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 17 Mosaicism?

The signs and symptoms of Trisomy 17 Mosaicism may vary in type and severity among affected individuals. Some of those with the condition may be asymptomatic, while others may present with the following signs and symptoms: 

• Developmental delays; slow growth
• Short stature
• Facial abnormalities including:
  • Facial asymmetry
  • Small-sized head (microcephaly)
  • Broad forehead
  • Horizontal palpebral fissures
  • Widely-spaced eyes (ocular hypertelorism)
  • Short bulbous nose
  • Anteverted nares
  • Abnormal ear lobes
  • Small or backwards positioned jaw (micrognathia/retrognathia)
• Body asymmetry
• Hand and foot abnormalities including:
  • Foot position abnormality
  • Hypoplastic nails
  • Postaxial polydactyly
  • Single palmar crease
• Hypertrichosis (increased sweating)
• Progressive hypotonia (poor muscle tone) causing motor delays that can be mild or severe. It can cause a variety of issues including:
  • Feeding problems (sucking and swallowing) leading to small and underweight children
  • Difficulty in holding small items such as a cup or spoon
  • Drawing and writing difficulties
  • Difficulty in climbing stairs and difficulty in sitting without support
  • Standing and walking difficulties
  • Help needed for wearing clothes and undressing
• Fontanelle: A large soft spot on head/skull that closes slowly
• Brain anomalies such as:
  • Dandy Walker variant
  • Decreased parenchymal brain volume
  • Cerebellar and pontine hypoplasia
  • Hydronephrosis
• Congenital heart abnormalities such as:
  • Single umbilical artery
  • Tetralogy of Fallot (TOF)
  • patent foramen ovale (PFO)
  • Ventricular septal defect (VSD)
  • Dilated coronary arteries
  • Concentric left ventricular hypertrophy
• Inguinal hernia
• Digestive system abnormalities including:
  • Gastroesophageal reflux disease (GERD)
  • Intestinal malrotation
• Moderate‐severe sensorineural hearing loss (SNHL)
• Cystic hygroma
• Fetal anomalies, such as increased nuchal thickening and nuchal redundancy, may be detected during prenatal evaluation

How is Trisomy 17 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 17 Mosaicism in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Trisomy 17 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 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: 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 Trisomy 17 Mosaicism?

The complications of Trisomy 17 Mosaicism may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR); some babies are underweight at birth
• Delayed milestone achievement
• Poor growth due to malnutrition caused by weak suckling
• Deafness
• Problems with movement and balance due to cerebellar hypoplasia
• Severe heart and brain abnormalities
• Low self-esteem, due to abnormalities in physical appearance 
• Reduced quality of life

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

How is Trisomy 17 Mosaicism Treated?

There is no cure for Trisomy 17 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 17 Mosaicism may involve:

• Use of hearing aids, if required
• Employing learning strategies via music therapy, visual and tactile books, touch screen computers, etc.
• Speech and language therapy
• Physiotherapy for weakened muscles, including incorporating daily exercise regimen
• Development of motor skills via daily exercises, swimming, 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
• For feeding difficulties, use of feeding tubes (temporary), medications, feed thickeners, including special diets and nutritional supplements
• A surgical procedure named fundoplication may be necessary in some children with severe GERD. Milder GERD cases can be generally well-controlled by giving feeds slowly and positioning the baby in a semi-upright. And, where necessary, raising the head of the end of the bed for sleeping is also recommended
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time
• Surgical correction of physical defects, as assessed by a healthcare expert
• 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 Trisomy 17 Mosaicism be Prevented?

Trisomy 17 Mosaicism may not be preventable since many of these genetic disorders are diagnosed at or following the birth of the child.

• A vast 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

It is important to note that the chances of both the parents with normal chromosomes having another child with Mosaic Trisomy 17 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 Trisomy 17 Mosaicism? (Outcomes/Resolutions)

The long-term outlook for individuals with Trisomy 17 Mosaicism varies from one child to another. It largely depends on the variety and severity of signs and symptoms present in the child.

• However, early diagnosis and treatment can improve survival and quality of life for affected people
• Most children usually require lifelong medical support and care

Additional and Relevant Useful Information for Trisomy 17 Mosaicism:

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

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