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

• 16p Duplication Syndrome
• Partial Trisomy 16p Syndrome
• Trisomy 16p Syndrome

What is Chromosome 16p Duplication Syndrome? (Definition/Background Information)

• Chromosome 16p Duplication Syndrome is a rare chromosomal disorder caused by the presence of an extra copy of a small piece of chromosome 16 (on the short arm p) in the cells of the body leading to a set of associated signs and symptoms. These may be mild or severe, depending on several factors such as the amount of genetic material gained (duplicated), the number of genes affected, and the function of the affected genes
• The condition affects newborn children (congenital manifestation). In 16p Duplication Syndrome, there is duplication of chromosomal material on the short arm (p) of one of the chromosomes 16. Every cell has two copies of chromosome 16s. Typically, small duplications do not present any major or significant health concerns. When large duplications are noted, the presentations may be severe
• The signs and symptoms that are noted in individuals with Chromosome 16p Duplication Syndrome include growth and developmental delays, abnormal facial features, intellectual challenges, and behavioral issues. It can result in severe complications without adequate treatment support
• This chromosomal anomaly may develop from sporadic mutations (vast majority of cases), or it may be inherited from one’s parents (very rarely). 16p Duplication Syndrome may be diagnosed through specialized genetic testing. In some children, the condition may be mild and hence can also remain undiagnosed
• 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, physiotherapy, and surgery for correction of defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 16p Duplications Syndrome are able to cope well through adequate treatment and supportive care. Some of the abnormalities are known to improve with time

Who gets Chromosome 16p Duplication Syndrome? (Age and Sex Distribution)

• Chromosome 16p Duplication 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 Chromosome 16p Duplication Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 16p Duplication Syndrome.

• A positive family history may be an important risk factor since 16p Duplication Syndrome 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 Chromosome 16p Duplication Syndrome? (Etiology)

Chromosome 16p Duplication Syndrome is caused by duplication of genetic material in the short arm (p) of chromosome 16.

• The duplication of genetic material occurs spontaneously (de novo) in majority of cases
• In some cases, however, the condition may be caused by heritable changes passed from a parent with the syndrome in which a subsequent chromosomal re-arrangement has led to a balanced translocation (in some rare cases)
  • If the chromosomal re-arrangement does not result in a net gain or loss of genetic material, it is known as a “balanced translocation”
  • Those with balanced translocation of 16p can have abnormalities in the development of egg or sperm, causing the disorder in their offspring
• There are two chromosomes numbered 16. Children with 16p Duplication Syndrome typically will have one (chromosome 16) in normal condition, while the other is abnormal. The abnormality is characterized by a gain of chromosomal material
• It is observed that when the duplication of material occurs at the tip of the chromosome, the conditions are generally mild. In severe cases, where large duplications are noted (or the centromere, present in the middle portion of the chromosome, is involved), the child may be severely affected

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.

A chromosome duplication disorder indicates that a certain portion of the chromosomal material is duplicated, which may be detected through molecular genetic testing. Depending on the nature and amount of extra material, the manifestation of a set of signs and symptoms are noted.

What are the Signs and Symptoms of Chromosome 16p Duplication Syndrome?

The signs and symptoms of Chromosome 16p Duplication Syndrome may be significantly different from one individual to another. The degree of signs and symptoms are often related to the amount of chromosome material added and the number of genes affected. As a general rule, a small gain in chromosome material generally results in milder signs and symptoms. Conversely, larger gains/duplications of the chromosome material generally results in severe signs and symptoms. It is important to note that exceptions may also occur, where individuals with small amount of chromosomal gains, may have disproportionately severe presentations.

The associated signs and symptoms depend on what material is duplicated, how much (quantity), where the duplications occurs (such as at the tip or center of the chromosome), and if the involvement of another chromosome is noted (that may occur in some cases).

The commonly noted signs and symptoms of Chromosome 16p Duplication Syndrome include:

• In some children, small-sized head with respect to the body is noted
• Distinctive facial features may include receding small lower jaw and small chin; cleft palate and high palate; low-set ears and nose abnormal in appearance
• Short stature
• Severe feeding difficulties (including due to abnormal jaw structure)
• Hand and foot joints may be in bent or fixed position
• Presence of abnormal hands and feet
• Speech and learning disabilities, which may be highly variable based on the amount and location of duplication of chromosome material
• Hydrocephalus - presence of excess cerebrospinal fluid around the brain
• Heart abnormalities may result in associated signs and symptoms, such as chest pain, shortness of breath, dizziness, fainting, palpitations, and tiredness, among others
• Seizures in some children
• Vision impairment
• Intellectual disability
• Behavioral issues may be noted

How is Chromosome 16p Duplication 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 Chromosome 16p Duplication Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 16p Duplication 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 assessment through various tests
• Eye and vision assessment
• 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
• 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 Chromosome 16p Duplication Syndrome?

The complications of Chromosome 16p Duplication Syndrome may include:

• Severe emotional stress for parents and caregivers
• Failure to thrive
• Weak immune causing severe vulnerability to infections
• Delayed milestone achievement
• Inability to live independently
• Severe heart anomalies
• Severe intellectual deficiency
• Inappropriate or violent behavior
• Physical abnormalities that can cause difficulties in day-to-day living
• Reduced quality of life

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

How is Chromosome 16p Duplication Syndrome Treated?

There is no cure for Chromosome 16p Duplication 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 16p Duplication 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
• Employing learning strategies via music therapy, visual and tactile books, touch screen computers, etc.
• Speech and language therapy; the use of sign language may be beneficial
• 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
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time
• Surgical treatment for hydrocephalus
• Surgical correction of physical defects, as assessed by a healthcare expert, such as surgical repair of cleft lip
• Use of suitable glasses and surgical rectification of vision defects
• 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 Chromosome 16p Duplication Syndrome be Prevented?

Chromosome 16p Duplication 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 Chromosome 16p Duplication 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 Chromosome 16p Duplication Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 16p Duplication 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 outcomes, especially on a long-term basis.

• Children with mild conditions are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Some children are known to require lifelong medical support and care

Additional and Relevant Useful Information for Chromosome 16p Duplication Syndrome:

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

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