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

• Chromosome 15q Tetrasomy
• Idic(15)
• Supernumerary Marker 15 (SMC (15))

What is Isodicentric Chromosome 15 Syndrome? (Definition/Background Information)

• Isodicentric Chromosome 15 Syndrome, or Idic(15), is a rare genetic abnormality involving chromosome 15 that affects many different body systems. In Idic(15), there is a small extra piece of chromosome 15 that is duplicated in an inverted manner (end-to-end) in some of the cells
• The condition affects newborn children (congenital manifestation). It can result in a variety of associated signs and symptoms that include developmental delays, speech and learning challenges, poor muscle tone or hypotonia, behavioral issues, and intellectual disability that may be severe. When large duplications are noted, the presentations may be severe
• This chromosomal anomaly may develop from sporadic mutations (vast majority of cases), or it may be inherited from one’s parents (very rarely). Isodicentric Chromosome 15 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 heart and other defects
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Isodicentric Chromosome 15 Syndrome are able to cope well through adequate treatment and supportive care. Some of the signs and symptoms associated with the condition are known to improve with time

Who gets Isodicentric Chromosome 15 Syndrome? (Age and Sex Distribution)

• Isodicentric Chromosome 15 Syndrome is a rare congenital disorder, occurring at a frequency of approximately 1:30,000
• 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
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Isodicentric Chromosome 15 Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Isodicentric Chromosome 15 Syndrome.

• In some individuals, a positive family history may be an important risk factor for the condition
• 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 Isodicentric Chromosome 15 Syndrome? (Etiology)

The cause of Isodicentric Chromosome 15 Syndrome is not well-understood.

• Most cases of the disorder occur spontaneously during the formation of the eggs or sperms. Typically, the condition is not inherited and occurs in individuals with no family history of the disorder
• There are two chromosomes numbered 15. Children with 1p Duplication Syndrome typically will have one (chromosome 15) in normal condition, while the other is abnormal. The abnormality is characterized by a gain of chromosomal material
• Since the amount of genetic material duplicated, the number of genes affected, and the function of the affected genes can vary from one individual to another, Isodicentric Chromosome 15 Syndrome can present a set of widely varying symptoms
  • Individuals with mosaicism, where duplication of chromosome 15 is observed only in some of the cells, tend to have much milder signs and symptoms
  • If the duplications arise from the father, no significant developmental anomalies are generally noted; but, when they arise from the mother, the disorder is associated with developmental issues (probably due to involvement of two maternally-expressed genes called the UBE3A gene and ATP10A gene)
  • Children with interstitial duplications (int dup(15)), where the segment of additional chromosome material is present within chromosome 15, also show milder signs and symptoms
  • If the critical region called 15q11q13, also termed Prader-Willi and Angelman critical region (PWACR), which contains over 20 genes is not involved/duplicated, then typically no signs and symptoms are seen. However, a majority of Isodicentric Chromosome 15 Syndrome cases are associated with 15q11q13 duplication

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 Isodicentric Chromosome 15 Syndrome?

The signs and symptoms of Isodicentric Chromosome 15 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.

The signs and symptoms of Isodicentric Chromosome 15 Syndrome may include:

• Hypotonia in newborns (poor muscle tone); floppiness in babies
• Delayed development in many children
• Learning disabilities, which may vary from mild to severe, are observed in nearly all children
• Poor fine and gross motor skills
• Vision impairment mostly includes strabismus, longsightedness, shortsightedness, and astigmatism
• Some degree of hearing loss is observed in almost 35% of the cases; this is mostly caused by a condition known as glue ear (fluid buildup in the middle ear)
• Undescended testes and other genital defects, typically in boys
• Feeding difficulties (chewing and swallowing difficulties), including gastroesophageal reflux disease (GERD)
• Constipation may be seen in many children with poor muscle tone
• Intellectual deficiency
• Problems with development of speech is noted in nearly all cases; speech delay - most children learn to speak around age 2-3 years
• Behavioral issues, such as hypersensitivity, anxiety, and attention deficiency hyperactivity syndrome (ADHD), may be seen in some children
• Autistic spectrum disorder
• Seizures are observed in more than 50% of the cases
• Heart abnormalities are rarely noted
• Oral and dental health issues may include cleft palate and missing teeth
• Eczema, which may be mild or severe
• Sleep disturbances

How is Isodicentric Chromosome 15 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 Isodicentric Chromosome 15 Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Isodicentric Chromosome 15 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
• 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 Isodicentric Chromosome 15 Syndrome?

The complications of Isodicentric Chromosome 15 Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications in some cases
• Lack of speech development
• Delayed milestone achievement - the child may take much longer to roll, sit, and walk than other babies of same age group
• Increased pain tolerance
• Deafness
• Problems with movement due to low muscle tone; walking and climbing staircases are often difficult
• Risk of falls and injury due to seizures
• Abnormal spinal curvature, such as scoliosis, is noted in nearly one-fifth of the cases
• Crowding of organs in the chest cavity due to scoliosis, which can severely affect the functioning of the heart and lungs
• Penile abnormalities such as micropenis and paraphimosis
• Severe intellectual deficiency
• Reduced quality of life

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

How is Isodicentric Chromosome 15 Syndrome Treated?

There is no cure for Isodicentric Chromosome 15 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 Isodicentric Chromosome 15 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
• 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
• Severe constipation may require dietary changes, including increased intake of fiber and wholegrains, along-with the administration of laxatives
• A surgical procedure named fundoplication may be necessary in some children with severe gastroesophageal reflux disease (GERD). Milder GERD cases can be generally well-controlled by giving feeds slowly and positioning the baby in a semi-upright position
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time
• Surgical correction (orchiopexy) of undescended testicles and other genital defects
• Surgical correction of physical defects, as assessed by a healthcare expert, such as surgical repair of cleft lip
• Use of padded brace for abnormal spinal curvature and posture management, including surgical correction of severe cases. Also, children may be provided specially designed furniture, such as chairs, tables, and beds, for spine support while sitting and sleeping
• Use of suitable glasses and surgical rectification of vision defects
• Sleep disorders may require medication; daytime naps may be advised
• 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 Isodicentric Chromosome 15 Syndrome be Prevented?

Isodicentric Chromosome 15 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.

• Prenatal diagnosis (molecular testing of the fetus during pregnancy) 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 Isodicentric Chromosome 15 Syndrome? (Outcomes/Resolutions)

The prognosis of Isodicentric Chromosome 15 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 is generally difficult to predict the long-term outlook
• Many children generally require lifelong medical support and care

Additional and Relevant Useful Information for Isodicentric Chromosome 15 Syndrome:

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

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