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

• 15q13.3 Microdeletion Syndrome
• Chromosome 15q13.3 Deletion Syndrome

What is Chromosome 15q13.3 Microdeletion Syndrome? (Definition/Background Information)

• Chromosome 15q13.3 Microdeletion Syndrome is a rare chromosome abnormality that develops when there is missing genetic material on chromosome 15 leading to a set of associated signs and symptoms. Specifically, a small segment of genetic material on the long arm (or q arm) of chromosome 15 at position q13.3 is missing or is deleted
• Some individuals with this deletion may have only mild features, while others may have mild to severe findings that can include growth and developmental delays, seizures, intellectual disability of varying severity, abnormal facial features, behavioral issues, and other physical defects
• This chromosomal anomaly is known to develop from sporadic mutations or inherited from one’s parents (very rarely). 15q13.3 Microdeletion 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 hearing and vision aids, behavioral 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 15q13.3 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 15q13.3 Microdeletion Syndrome? (Age and Sex Distribution)

• Chromosome 15q13.3 Microdeletion 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 Chromosome 15q13.3 Microdeletion Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 15q13.3 Microdeletion Syndrome.

• A positive family history may be an important risk factor since 15q13.3 Microdeletion Syndrome can be 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 15q13.3 Microdeletion Syndrome? (Etiology)

• Chromosome 15q13.3 Microdeletion Syndrome is caused by a deletion of genetic material in the long arm (q) of chromosome 15. The deletion typically occurs in one of the 2 copies of chromosome 15, and the missing segment corresponds to band q13.3
• The q13.3 region is known to contain at least six (or more) genes that may be affected. These include MTMR10, TRPM1, KlF13, TUD7A and CHRNA7 genes
• 15q13.3 Microdeletion Syndrome can occur in an individual as a consequence of the following:
• A random event in the egg or sperm in a parent 
• A random event in the early stages of embryonic development
• An inherited deletion from a parent (seen in 50% of the recorded cases) - in such cases, the condition is inherited in an autosomal dominant manner with reduced penetrance
• 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.

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

In autosomal dominant inheritance with reduced or incomplete penetrance, an individual may not develop symptoms even when he/she is carrying a gene mutation or deletion in each cell of his/her body

What are the Signs and Symptoms of Chromosome 15q13.3 Microdeletion Syndrome?

The signs and symptoms of Chromosome 15q13.3 Microdeletion Syndrome may be different from one individual to another. The degree of signs and symptoms are often related to the amount of chromosome material gained and the number of genes affected/involved. Nevertheless, many individuals with this microduplication syndrome have very mild presentations with no major birth defects being observed.

The commonly noted signs and symptoms of Chromosome 15q13.3 Microduplication Syndrome include:

• Development delays; short stature
• Abnormal facial features that include:
  • Small-sized or large-sized head
  • Downslanting eyes; skin folds near the corner of the eyes
  • Prominent forehead
  • Abnormal-shaped protruding ears; sometimes they are small in size
  • Abnormal nose tip
• Feeding difficulties due to swallowing difficulties
• Heart abnormalities that can result in associated signs and symptoms, such as chest pain, shortness of breath, dizziness, fainting, palpitations, and tiredness, among others
• Intellectual disability that may be mild, moderate, or severe
• Learning disabilities
• Behavioral issues that include:
  • Attention-deficit hyperactivity disorder (ADHD)
  • Bipolar affective disorder
  • Schizophrenia
• Seizures
• Vision impairment such as strabismus
• Skin conditions such as melanocytic nevus
• Low muscle tone
• Abnormalities involving the hands and feet

How is Chromosome 15q13.3 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 Chromosome 15q13.3 Microdeletion Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

15q13.3 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
• Hearing and vision assessment
• Assessment of cardiac function
• 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 Chromosome 15q13.3 Microdeletion Syndrome?

The potential complications of Chromosome 15q13.3 Microdeletion Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Delay in reaching developmental milestones
• Low self-esteem because of one’s appearance
• Severe behavioral issues
• Risk of falls and injury due to seizures
• Overall reduced quality of life

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

How is Chromosome 15q13.3 Microdeletion Syndrome Treated?

There is no cure for Chromosome 15q13.3 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, cardiologists, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for 15q13.3 Microdeletion Syndrome may involve:

• Use of hearing aids, if required
• Employing suitable 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 stiff muscles, including incorporating daily exercise regimen
• Development of motor skills via daily exercises, swimming, and other adapted activities
• For feeding difficulties, use of feeding tubes (temporary), medications, feed thickeners, including special diets and nutritional supplements
• Surgical correction of physical defects, as assessed by a healthcare expert
• Use of suitable glasses and rectification of vision defects
• Heart abnormalities may require surgical correction in some cases
• 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 Chromosome 15q13.3 Microdeletion Syndrome be Prevented?

Chromosome 15q13.3 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), if available, 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 15q13.3 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 15q13.3 Microdeletion Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 15q13.3 Microdeletion Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any.

• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis, and it is generally difficult to predict the long-term outlook
• Some of the abnormalities are known to resolve or improve with time. But some children may require lifelong medical support and care

Additional and Relevant Useful Information for Chromosome 15q13.3 Microdeletion Syndrome:

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

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