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

• R16 Syndrome
• Ring 16 Syndrome

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

• Ring Chromosome 16 Syndrome is a very rare chromosome abnormality in which the ends of chromosome 16 join together to form a ring shape. It is characterized by pre- and postnatal growth delay, severe developmental delay, intellectual disability, speech delay, and craniofacial abnormalities
• Ring Chromosome 16 Syndrome typically is not inherited and occurs sporadically (de novo), during the formation of egg or sperm cells or shortly after the egg and sperm fuse together. The disorder may be diagnosed through specialized genetic testing
• 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 speech and language therapy, 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 Ring Chromosome 16 Syndrome are able to cope well through adequate treatment and supportive care. However, in some cases, children are not known to survive the condition

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

• Ring Chromosome 16 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 Ring Chromosome 16 Syndrome? (Predisposing Factors)

Currently, no risk factors have been clearly identified for Ring Chromosome 16 Syndrome.

• A positive family history may be an important risk factor. However, currently no cases of inherited Ring Chromosome 16 Syndrome have been reported
• 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 Ring Chromosome 16 Syndrome? (Etiology)

Ring Chromosome 16 Syndrome is caused by an abnormal chromosome known as a ring chromosome 16 or r(16).

• A ring chromosome is a circular structure that occurs when a chromosome breaks in two places and the broken ends fuse together
• The features of Ring 16 Syndrome may result from the partial deletion of genetic material from chromosome 16. Since the breakpoints may vary widely, the features are also markedly different in the affected individuals
• Ring Chromosome 16 Syndrome is usually caused by spontaneous (de novo) errors in the egg or sperm; or it can occur very early in embryonic development, and therefore, be sporadic in nature. A family history of the disorder is not yet recorded in the medical literature

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 161 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 Ring Chromosome 16 Syndrome?

The signs and symptoms of Ring Chromosome 16 Syndrome may vary widely 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 condition is known to be asymptomatic in some, but may result in the following signs and symptoms in others: 

• Growth and developmental delays that may be severe
• Intellectual disability
• Speech delay
• Craniofacial abnormalities (dysmorphism):
• Microcephaly (small-sized head)
• Hypertelorism (widely-spaced eyes); unibrow
• Drooping eyelid (ptosis)
• Low set and abnormal shape ears 
• Broad flat nasal bridge
• Down-turned mouth corners
• High palate 
• Lower jaw is set back from the face (retrognathia)
• Congenital cataract
• Poor muscle tone (hypotonia)
• Poor social contact and social isolation
• Congenital heart anomalies such as ventricular septal defect (VSD) and patent ductus arteriosus (PDA)

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

Ring 16 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 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 (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
• 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 Ring Chromosome 16 Syndrome?

The complications of Ring Chromosome 16 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
• Severe intellectual deficiency
• Impaired vision
• Social isolation
• Abnormal heart rhythm and heart attack
• Reduced quality of life

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

How is Ring Chromosome 16 Syndrome Treated?

There is no cure for Ring Chromosome 16 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 Ring 16 Syndrome may involve:

• Employing suitable 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 
• 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)
• 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
• Surgical correction of kidney issues, as necessary
• Hernia repair surgery for umbilical and 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 Ring Chromosome 16 Syndrome be Prevented?

Ring Chromosome 16 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.

• 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

What is the Prognosis of Ring Chromosome 16 Syndrome? (Outcomes/Resolutions)

The prognosis of Ring Chromosome 16 Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any. Typically, the prognosis may be assessed on a case-by-case basis.

• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Some children may require lifelong medical support and care

Additional and Relevant Useful Information for Ring Chromosome 16 Syndrome:

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

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