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

• R2 Syndrome
• Ring 2 Syndrome

What is Ring Chromosome 2 Syndrome? (Definition/Background Information)

• Ring Chromosome 2 Syndrome is a highly uncommon abnormality involving chromosome 2; wherein, the broken ends of a chromosome fuse together to form a circular (ring) shape. In Ring 2 Syndrome, there may be a loss of chromosome material at the broken end, causing an associated set of signs and symptoms
• The presentations of Ring Chromosome 2 Syndrome may include pregnancy complications, low muscle tone, distinctive facial features, skeletal defects, and short stature. Significant birth defects are generally not reported in children with this disorder, although some report heart defects
• Ring Chromosome 2 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, if any
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Ring Chromosome 2 Syndrome are able to cope well through adequate treatment and supportive care. However, in some rare cases, children are not known to survive the condition

Who gets Ring Chromosome 2 Syndrome? (Age and Sex Distribution)

• Ring Chromosome 2 Syndrome is an extremely rare congenital disorder, with fewer than 20 cases reported in the medical literature
• 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
• The presentation of symptoms may occur at or following the birth of the child
• Both males and females may be affected
• Individuals of all racial and ethnic groups may be affected

What are the Risk Factors of Ring Chromosome 2 Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Ring Chromosome 2 Syndrome.

• A positive family history may be an important risk factor. However, currently no cases of inherited Ring 2 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 2 Syndrome? (Etiology)

Ring Chromosome 2 Syndrome is caused by an abnormal chromosome formation known as a ring chromosome 2 or r(2).

• 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 the syndrome may result from the loss (deletion) of genetic material from chromosome 2, either at the short arm (p) or the long arm (q). In some cases, there may not be an apparent loss of chromosomal material
• According to medical literature, in a vast majority of cases, either of the chromosome bands at p25 or q37 have been involved, on the short arm or long arm respectively
• It is important to note that not all cells may present the ring chromosome 2, but only some cells may show r(2). This is known as mosaicism, and may play a role in the severity of the signs and symptoms
• Ring Chromosome 2 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 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 2 Syndrome?

The signs and symptoms of Ring Chromosome 2 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:

• Developmental delays; growth hormone deficiencies
• Feeding difficulties in infants and young children
• Small-sized head (microcephaly) with flat back of the head, and other abnormal facial features such as widely-set eyes, high-arched eyebrows, skin folds around the inner corners of the eye, low-set ears, small lower jaw and chin, and short neck
• Short stature
• Abnormalities involving the hands and feet, including rocker bottom feet, clubfoot, and flat feet
• Low muscle tone (hypotonia)
• Loose and flexible joints
• Skeletal abnormalities
• Heart defects may include ventricular septal defect (VSD), persistent ductus arteriosus (PDA), and coarctation of the aorta. These may result in associated signs and symptoms, such as chest pain, shortness of breath, dizziness, fainting, palpitations, and tiredness, among others
• Umbilical and inguinal hernias
• Nearly 75% children show minor genital abnormalities
• Café au lait spots on skin
• Learning difficulties, generally mild or moderate
• Speech and communication challenges
• Behavioral abnormalities such as autism
• Some children may report minor vision defects such as strabismus
• Hearing impairment due to glue ear is commonly seen

How is Ring Chromosome 2 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 2 Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Ring Chromosome 2 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 2 Syndrome?

The complications of Ring Chromosome 2 Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR); babies are typically small-sized and underweight at birth
• Failure to thrive
• Birth defects involving the heart, genitals, or other parts of the body
• Delayed milestone achievement; some children learn to walk when they reach age 2
• Heart ailments that may be severe
• Intellectual impairment
• Infertility
• Reduced quality of life

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

How is Ring Chromosome 2 Syndrome Treated?

There is no cure for Ring Chromosome 2 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 2 Syndrome may involve:

• Use of hearing aids; in case of fluid buildup in the middle ear, some children may require the placement of a small ventilation tubes to help with improved fluid drainage
• Special education: 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 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
• Hernia repair surgery for umbilical and inguinal hernias, as needed
• Use of suitable glasses for vision defects
• Surgical correction of genital 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 Ring Chromosome 2 Syndrome be Prevented?

Ring Chromosome 2 Syndrome 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.

• Genetic (chromosome) testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• 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 2 Syndrome? (Outcomes/Resolutions)

The prognosis of Ring Chromosome 2 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.

• Many affected children are reported to succumb to the condition; in most cases, they do not reach adulthood. The longest surviving individual diagnosed with this syndrome was reported to be about 35 years old
• Children with mild conditions are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Children usually require lifelong medical support and care; it may also take some children a long time (several years) to gain a measure of independence

However, in general, children with Ring Chromosome 2 Syndrome can be healthy, and no major birth defects may be noted.

Additional and Relevant Useful Information for Ring Chromosome 2 Syndrome:

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

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