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

• R9 Syndrome
• Ring 9 Syndrome

What is Ring Chromosome 9 Syndrome? (Definition/Background Information)

• Ring Chromosome 9 Syndrome is a rare chromosomal anomaly syndrome with variable presentations. In this disorder, the ends of chromosome 9 join together to form a ring shape. It is principally characterized by short stature, developmental delays, congenital heart and kidney defects, abnormal facial features, and behavioral issues
• Ring Chromosome 9 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, Ring 9 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 feeding support, physiotherapy, and surgery for correction of physical 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 9 Syndrome are able to cope well through adequate treatment and supportive care. Some of the abnormalities are known to improve with time

Who gets Ring Chromosome 9 Syndrome? (Age and Sex Distribution)

• Ring Chromosome 9 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 9 Syndrome? (Predisposing Factors)

Currently, no risk factors have been clearly identified for Ring Chromosome 9 Syndrome.

• A positive family history may be an important risk factor, although a vast majority of cases are known to occur sporadically
• 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 Ring Chromosome 9 Syndrome? (Etiology)

Ring Chromosome 9 Syndrome is caused by an abnormal chromosome known as a ring chromosome 9 or r(9).

• A ring chromosome is a circular structure that occurs when a chromosome breaks in two places and the broken ends fuse together. In the long arm (q), the breakpoints are typically between q33 and q34; while, in the short arm (p), it is between p22 and p24
• The features of the syndrome may result from the loss (deletion) or gains (duplication) of genetic material from chromosome 9. Also, since the breakpoints may vary widely, the features are also markedly different in the affected individuals
• In other words, the signs and symptoms may present similarities with individuals who have under gone 9p and 9q deletions, and 9p and 9q duplications
• In some cases, a complicated version of ring may form, termed “inv dup del”, with a part of chromosome tip being duplicated and placed inverted at another tip that is lost/deleted
• Ring 9 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 highly uncommon in this syndrome

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 Ring Chromosome 9 Syndrome?

The signs and symptoms of Ring Chromosome 9 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, the chromosome breakpoints, and the number of genes affected. The signs and symptoms may include:

• Short stature
• Developmental delay
• Abnormal facial features that include:
• Small-sized head or even keel-shaped head
• Arched and thick eyebrows
• Mildly bulging eyes; skin folds at inner corner of the eyes
• Wide nasal bridge
• Long upper lip
• Cleft palate
• Slightly receding jaw
• Poor muscle tone or hypotonia; some children present hypertonia (stiff muscles with limited range of movements)
• Feeding difficulties, including gastroesophageal reflux disease (GERD)
• Seizures may be noted in some children; seizure-like movements
• Minor genital abnormalities in boys such as hypospadias and undescended testicles
• In a few cases, heart abnormalities may be noted, which include:
  • Hole in the heart
  • Patent ductus arteriosus (PDA)
  • Tetralogy of Fallot
• Light or dark skin pigmentation patches
• Mild vision impairment (uncommon)
• Intestinal malrotation
• Intellectual disability
• Learning difficulties; delayed speech and communication
• Behavioral issues: Mood swings and anger outbursts have been reported in older children

How is Ring Chromosome 9 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 9 Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Ring Chromosome 9 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: 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 9 Syndrome?

The complications of Ring Chromosome 9 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
• Frequent and recurrent respiratory infections
• Severe hearing loss
• Abnormal spinal curvature (scoliosis)
• Kidney defects such as underdeveloped kidneys and kidney malfunction
• Severe intellectual disability (low IQ levels)
• Severe heart anomalies
• Reduced quality of life

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

How is Ring Chromosome 9 Syndrome Treated?

There is no cure for Ring Chromosome 9 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 9 Syndrome may involve:

• Use of hearing aids, as needed
• 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 
• 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
• 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
• 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 may improve over time without any invasive procedures
• Surgical correction (orchiopexy) of undescended testicles and other genital defects
• Use of suitable glasses and surgical rectification of vision defects, if necessary
• Hernia repair surgery for umbilical and inguinal hernias, as needed Surgical correction of physical defects, as assessed by a healthcare expert
• 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 9 Syndrome be Prevented?

Ring Chromosome 9 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 9 Syndrome? (Outcomes/Resolutions)

The prognosis of Ring Chromosome 9 Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any. Typically, the prognosis may be only assessed on a case-by-case basis.

• Children with mild conditions are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Some children may require lifelong medical support and care; it may also take some children a long time (several years) to gain a measure of independence

Additional and Relevant Useful Information for Ring Chromosome 9 Syndrome:

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

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