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

• Mosaic Trisomy Chromosome 14 Syndrome
• Trisomy 14 Mosaicism

What is Mosaic Trisomy 14 Syndrome? (Definition/Background Information)

• Mosaic Trisomy 14 Syndrome is a rare chromosomal disorder in which there are 3 copies (trisomy) of chromosome 14 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
• The signs and symptoms of Mosaic Trisomy 14 Syndrome that have been most commonly reported include intrauterine growth restriction, failure to thrive, developmental delay, intellectual disability, distinctive facial characteristics, malformations of the heart, and other physical abnormalities
• 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

(Source: Mosaic Trisomy 14 Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

• Thus, a vast majority of cases are not inherited. Following a diagnosis, Mosaic Trisomy 14 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 heart 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 Mosaic Trisomy 14 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 14 Syndrome? (Age and Sex Distribution)

• Mosaic Trisomy 14 Syndrome is a rare congenital disorder. The presentation of symptoms may occur at 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
• 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 14 Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Mosaic Trisomy 14 Syndrome.

• A positive family history may be an important risk factor since Trisomy 14 Mosaicism can be inherited. However, presently no cases of inheritance are recorded in the medical literature

• 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 14 Syndrome? (Etiology)

• Individuals with Mosaic Trisomy 14 Syndrome have a duplication of chromosome 14 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 Mosaic Trisomy 14 Syndrome appear to result from random errors in the separation of chromosomes (nondisjunction) -- either during the division of the egg or sperm in one of the parents, or during cell division after fertilization. There have been some reports in which it may have occurred due to other phenomenon, such as uniparental disomy or the formation of an isochromosome
• Uniparental disomy is when an affected individual inherits both copies of a chromosomal pair from one parent, rather than one copy from each parent. An isochromosome is an abnormal chromosome with identical arms on each side of the centromere

(Source: Mosaic Trisomy 14 Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

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 14 Syndrome?

The signs and symptoms of Mosaic Trisomy 14 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:

• Facial feature abnormalities such as:
  • Large and prominent forehead
  • Wide mouth
  • High palate
  • Wide nasal bridge
  • Widely spaced eyes
  • Drooping eyelid
  • Low-set rotated ears
  • Small jaw
  • Short neck
• Feeding difficulties
• Slightly asymmetrical growth (limb asymmetry)
• Abnormal skin pigmentation
• Heart abnormalities such as tetralogy of Fallot
• Intellectual disability
• Some degree of developmental delay or intellectual disability
• Minor genital abnormalities in boys such as undescended testes and hypospadias
• Skeletal abnormalities such as dislocation of the hips and rib anomalies
• Ectopic anus
• Narrow chest
• Seizures

How is Mosaic Trisomy 14 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 14 Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Mosaic Trisomy 14 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 14 Syndrome?

The complications of Mosaic Trisomy 14 Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth restriction (IUGR)
• Failure to thrive
• Physical and mental growth retardation
• Recurrent respiratory infections
• Vision impairment due to under-developed eye
• Reduced quality of life

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

How is Mosaic Trisomy 14 Syndrome Treated?

There is no cure for Mosaic Trisomy 14 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 14 Syndrome may involve:

• Use of hearing aids, if needed
• 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
• 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
• Antibiotic therapy to treat infections, including instituting prophylactic treatment measures
• 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 14 Syndrome be Prevented?

Mosaic Trisomy 14 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:

• 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 14 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 14 Syndrome? (Outcomes/Resolutions)

The prognosis of Mosaic Trisomy 14 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
• In some cases, children require lifelong medical support and care; it may also take some children a long time (often several years) to gain a measure of independence

Additional and Relevant Useful Information for Mosaic Trisomy 14 Syndrome:

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

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