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

• SRC1 (Supernumerary Ring Chromosome 1)
• SRC1 Syndrome
• Supernumerary Ring Chromosome 1

What is Supernumerary Ring Chromosome 1 Syndrome? (Definition/Background Information)

• Supernumerary Ring Chromosome 1 (SRC1) Syndrome is a very rare chromosome abnormality in which there is an extra (but tiny) amount of genetic material of chromosome 1 that forms a ring shape (in some cells), in addition to the 46 chromosomes normally found in all the cells
• The presentations of Supernumerary Ring Chromosome 1 include pregnancy complications, feeding difficulties, low muscle tone, distinctive facial features, and birth defects
• Supernumerary Ring Chromosome 1 Syndrome is typically 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 the birth defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Supernumerary Ring Chromosome 1 Syndrome are able to cope well through adequate treatment and supportive care

Who gets for Supernumerary Ring Chromosome 1 Syndrome? (Age and Sex Distribution)

• Supernumerary Ring Chromosome 1 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 Supernumerary Ring Chromosome 1 Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Supernumerary Ring Chromosome 1 (SRC1) Syndrome.

• In some individuals, a positive family history may be an important risk factor for SRC1 Syndrome
• 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 Supernumerary Ring Chromosome 1 Syndrome? (Etiology)

Supernumerary Ring Chromosome 1 (SRC1) Syndrome is caused by an abnormal chromosome formation in which an extra part of chromosome 1 forms a ring shape. Presently, the reason why this takes place is not well-understood.

• A ring chromosome is a circular structure that occurs when a chromosome breaks in two places and the broken ends fuse together. In many children, not all cells present the extra ring chromosome; most cells present a normal make-up of 46 chromosomes. This feature is known as mosaicism
• The features of SRC1 syndrome may result from the loss (deletion) of genetic material from chromosome 1, either at the short arm (p) or the long arm (q). Occasionally, breakpoints may be noticed in both arms of the chromosome
• However, rarely, some chromosome bands contain no significant genetic material; while, in many cases, active genetic material is present. The manifestation of signs and symptoms are also dependent on these factors, and accordingly:
  • Growth and development may be affected if the duplicated band region contains active genetic material and important genes (termed heterochromatin bands)
  • Growth and development is not significantly affected if the duplicated band region contains no active genetic material and important genes (termed euchromatin bands)
• Supernumerary Ring Chromosome 1 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
• Rarely, a positive family history of the disorder may be noted, and the condition can be inherited from one’s parents

In ring chromosome, a very tiny part of the chromosome is duplicated such that it is not even visible under a microscope with high magnification. In such cases, FISH or array-CGH studies may be necessary to detect the abnormality.

Occasionally, SRC1 may occur from a condition termed uniparental disomy (UPD). In UPD, both the chromosome 1 pair comes from one parent (i.e., either the mother or the father). However, the supernumerary ring chromosome is from a different parent. This may result in additional and/or variable signs and symptoms. It is reported that nearly 10% of SRC1 Syndromes may take place in this manner.

The signs and symptoms of a ring chromosome are dependent upon the following factors:

• The quantity of ring material present
• If the ring contains active or inactive genetic material from the short arm (p) and/or the long arm (q)
• If the ring forms at the p arm or the q arm, and the interaction between each other (the ring and the short/long arm)
• The degree of mosaicism, meaning what percentage of cells contain the abnormality
• If uniparental disomy is observed or not 

Generally, if the ring contains genetic material from around the centromere, or inactive genetic material from any of the short or long arms, the growth and development of the fetus/child may not be significantly 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.

What are the Signs and Symptoms of Supernumerary Ring Chromosome 1 Syndrome?

The signs and symptoms of Supernumerary Ring Chromosome 1 Syndrome may vary widely among affected individuals in type and severity. The severity of the signs and symptoms are often related to the location of the ring, the amount of chromosome material involved, the number and function of the genes affected, the degree of mosaicism, and uniparental disomy (if noted).

The syndrome is rarely known to be asymptomatic in some individuals, but may result in the following signs and symptoms in others:

• Learning difficulties, usually mild or moderate
• Feeding difficulties in babies and young children
• Developmental delay
• Small-sized head (microcephaly)
• Short stature; short hands and feet
• Low muscle tone (hypotonia); floppiness of the baby
• Vision defects such as glaucoma and cataract
• Loose and flexible joints
• Distinctive facial features
• Skeletal abnormalities
• Seizures, in some children
• Behavioral abnormalities such as autism
• Heart anomalies, such as septal defects, which may result in associated signs and symptoms, such as chest pain, shortness of breath, dizziness, fainting, palpitations, and tiredness
• Minor genital anomalies, especially in boys
• Rarely, intestinal abnormalities such as malrotation of the intestine and volvulus
• Ear infections
• Diaphragmatic hernia and inguinal hernia

How is Supernumerary Ring Chromosome 1 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 Supernumerary Ring Chromosome 1 Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Supernumerary Ring Chromosome 1 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
• 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
• Heart defect evaluation
• 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 Supernumerary Ring Chromosome 1 Syndrome?

The complications of Supernumerary Ring Chromosome 1 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
• Delayed milestone achievement; walking difficulties may persist for some children
• Abnormal spinal curvature (kyphosis)
• Frequent respiratory infections
• Intellectual impairment
• Infertility may be commonly observed
• Reduced quality of life

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

How is Supernumerary Ring Chromosome 1 Syndrome Treated?

There is no cure for Supernumerary Ring Chromosome 1 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 Supernumerary Ring Chromosome 1 may involve:

• 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 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
• Surgical correction of physical defects, including heart surgery (if needed), as assessed by a healthcare expert
• 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 Supernumerary Ring Chromosome 1 Syndrome be Prevented?

Supernumerary Ring Chromosome 1 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 (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 Supernumerary Ring Chromosome 1 Syndrome? (Outcomes/Resolutions)

The prognosis of Supernumerary Ring Chromosome 1 (SRC1) Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any. Typically, the long-term 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
• Children usually require lifelong medical support and care. Severe cases are known to result in fatalities

The prognosis of SRC1 Syndrome is mainly based on the following factors (that determine the severity of the presentations of the disorder):

• Location of the ring
• Chromosome material (quantity) involved
• Number and function of the genes affected
• Degree of mosaicism
• Uniparental disomy (if present)

Additional and Relevant Useful Information for Supernumerary Ring Chromosome 1 Syndrome:

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

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