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

• 15q25.2 Deletion Syndrome
• 15q25.2 Microdeletion Syndrome

What is Chromosome 15q25.2 Microdeletion Syndrome? (Definition/Background Information)

• Chromosome 15q25.2 Microdeletion Syndrome is a chromosome abnormality that can affect many parts of the body. Individuals with this condition are missing a small piece (deletion) of chromosome 15 at location q25.2
• The signs and symptoms vary but usually include mild to moderate intellectual disability and developmental delay. Some individuals may also have poor growth, anemia, and/or physical abnormalities
• Chromosome 15q25.2 Microdeletion Syndrome often occurs sporadically as a random event during formation of the egg or sperm. In this case, an individual would have no family history of the condition but could pass the deletion on to their children. The disorder is usually not inherited
• 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 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 Chromosome 15q25.2 Microdeletion 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 Chromosome 15q25.2 Microdeletion Syndrome? (Age and Sex Distribution)

• Chromosome 15q25.2 Microdeletion Syndrome is a rare congenital disorder, with only less than 10 cases being reported worldwide
• 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 Chromosome 15q25.2 Microdeletion Syndrome? (Predisposing Factors)

In a majority of individuals, there are no identified risk factors for Chromosome 15q25.2 Microdeletion Syndrome.

• A positive family history may be an important risk factor since 15q25.2 Microdeletion Syndrome can be rarely inherited
• 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 Chromosome 15q25.2 Microdeletion Syndrome? (Etiology)

Chromosome 15q25.2 Microdeletion Syndrome is caused by the deletion of genetic material in the long arm (q) of chromosome 15, at the genetic locus designated 25.2.

• In most cases, the deletion occurs as a random event (de novo). In rare cases, the deletion can occur in the egg or sperm cells of a parent. Although the parent may not be affected, the offspring can inherit the changes and develop 15q25.2 Microdeletion Syndrome
• The 15q25.2 locus houses 27 genes; the deletion of these genes is believed to cause the signs and symptoms of the syndrome
• In microdeletion, a very tiny part of the chromosome is lost or missing; when 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 deletions

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.

A chromosome deletion disorder indicates that a certain portion of the chromosomal material is missing, which may be detected through molecular genetic testing. Depending on the nature and amount of material deleted, the manifestation of a set of signs and symptoms are noted.

What are the Signs and Symptoms of Chromosome 15q25.2 Microdeletion Syndrome?

The signs and symptoms of Chromosome 15q25.2 Microdeletion 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 deleted and the number of genes affected. As a general rule, a small loss of chromosome material generally results in milder signs and symptoms. Conversely, larger deletion of the chromosome material generally results in severe signs and symptoms. It is important to note that exceptions may also occur, where individuals with small amount of chromosomal loss, may have disproportionately severe presentations.

The commonly noted signs and symptoms of Chromosome 15q25.2 Microdeletion Syndrome include:

• Developmental delays and poor growth
• Abnormal facial features including thin upper lip and short, webbed neck
• The bones and muscles may be affected in many children
• Undescended testes
• Limb (hands and feet) abnormalities
• Blood abnormalities such as anemia and blood clots
• Autism
• Mild to moderate intellectual disability
• Psychiatric issues such as anxiety, hyperactivity, and attention deficits
• Seizures may be observed in some children

How is Chromosome 15q25.2 Microdeletion 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 15q25.2 Microdeletion Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 15q25.2 Microdeletion 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
• 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
• Evaluation of heart defects through:
  • Chest X-rays
  • Echocardiogram
  • Electrocardiogram (EKG)
  • Cardiac catheterization
  • Fetal ultrasound for heart defects
• 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 Chromosome 15q25.2 Microdeletion Syndrome?

The complications of Chromosome 15q25.2 Microdeletion Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR)
• Extreme weakness and fainting episodes due to anemia
• Abnormal heart function due to structural defects in the organ
• Problems with movement 
• Risk of falls and injury due to seizures
• Increased risk of developing certain types of cancer such as acute myeloid leukemia or osteosarcoma

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

How is Chromosome 15q25.2 Microdeletion Syndrome Treated?

There is no cure for Chromosome 15q25.2 Microdeletion 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, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for Chromosome 15q25.2 Microdeletion Syndrome may involve:

• 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, 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, medications, feed thickeners, bottle-feeding expressed milk, including special diets and nutritional supplements
• Heart abnormalities may require surgical correction in some cases
• Surgical correction (orchiopexy) of undescended testicles and other genital defects
• Sleep disorders may require medication; daytime naps may be advised
• Psychotherapy, behavior modification, and establishing discipline techniques, as necessary
• Occupational therapy
• Periodic screening for any malignancies

Regular medical screening at periodic intervals with tests and physical examinations are necessary and highly recommended.

How can Chromosome 15q25.2 Microdeletion Syndrome be Prevented?

Chromosome 15q25.2 Microdeletion 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 testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• 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

It is important to note that the chances of both the parents with normal chromosomes having another child with Chromosome 15q25.2 Microdeletion Syndrome is highly unlikely. This may be confirmed via specialized prenatal testing and preimplantation genetic diagnosis (PGD), if needed. Prenatal tests may include chorionic villus sampling (CVS) and amniocentesis.

What is the Prognosis of Chromosome 15q25.2 Microdeletion Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 15q25.2 Microdeletion 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 it is generally difficult to predict the long-term outlook of the disorder.

Additional and Relevant Useful Information for Chromosome 15q25.2 Microdeletion Syndrome:

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

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