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

• 17p13.3 Microdeletion Syndrome

What is Chromosome 17p13.3 Microdeletion Syndrome? (Definition/Background Information)

• Chromosome 17p13.3 Microdeletion Syndrome is a rare chromosome abnormality that develops when there is missing genetic material on chromosome 17 leading to a set of associated signs and symptoms. Specifically, a small segment of genetic material on the short arm (or p arm) of chromosome 17 at position 13.3 is missing or is deleted
• Some individuals with this deletion have no observable features, while others have variable findings that can include growth and developmental delays (speech and motor delays), intellectual disabilities, distinctive facial features, and other physical defects
• This chromosomal anomaly is usually known to develop from sporadic mutations (vast majority of cases). 17p13.3 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, speech and language therapy, 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 Chromosome 17p13.3 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 17p13.3 Microdeletion Syndrome? (Age and Sex Distribution)

• The incidence of Chromosome 17p13.3 Microdeletion Syndrome is presently unknown
• 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
• 17p13.3 Microdeletion Syndrome is a congenital disorder and the presentation of symptoms may occur at or following the birth of the child. However, among the recorded cases, it is reported that a diagnosis took place between 6 months to 22 years depending on symptom manifestation and its severity
• 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 17p13.3 Microdeletion Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 17p13.3 Microdeletion Syndrome.

• A positive family history may be an important risk factor, since 17p13.3 Microdeletion Syndrome may be an inherited 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 Chromosome 17p13.3 Microdeletion Syndrome? (Etiology)

• Chromosome 17p13.3 Microdeletion Syndrome is caused by a deletion of genetic material in the short arm (p) of chromosome 17. The deletion typically occurs in one of the 2 copies of chromosome 17, and the missing segment corresponds to p13.3
• 17p13.3 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
• 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
• A deletion of a part of 17p13.3, including both the LIS1 (or PAFAH1B1) gene and YWHAE gene, is known as Miller-Dieker syndrome (MDS)

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 17p13.3 Microdeletion Syndrome?

The signs and symptoms of Chromosome 17p13.3 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 signs and symptoms of 17p13.3 Microdeletion Syndrome may vary from one individual to another and may include:

• Developmental delays, both prenatally and postnatally
• Speech and language delays
• Abnormal facial features that include:
  • Small-sized head with prominent forehead
  • Widely spaced eyes
  • Drooping eyelid (ptosis)
  • Low-set ears
  • Broad nose
  • Wide mouth
  • Chin and lower jaw may be receding
• Slim body with short stature
• Feeding difficulties, including gastroesophageal reflux disease (GERD)
• Constipation may be seen in some children
• Hand and foot deformities may be seen
• Vision and hearing loss are generally mild to moderate
• Heart defects such as patent ductus arteriosus (PDA) and patent foramen ovale (PFO)
• Low muscle tone (hypotonia) affecting fine motor skills, which is not very common among children with this disorder
• Epileptic seizures are noted in some cases
• Behavioral difficulties such as autistic spectrum disorder and depression
• Intellectual disability
• Sleep disturbance
• Genitourinary and kidney anomalies; minor genital abnormalities in boys
• Presence of sacral dimples (indentations in the skin of the lower back, at the base of the spine) in some cases
• Eczema (rare finding)

How is Chromosome 17p13.3 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 17p13.3 Microdeletion Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

17p13.3 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 through various tests
• Evaluation of heart defects if any
• 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 Chromosome 17p13.3 Microdeletion Syndrome?

The potential complications of Chromosome 17p13.3 Microdeletion Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR)
• Delay in achieving developmental milestones
• Failure to thrive
• Low self-esteem
• Behavioral issues
• If scoliosis is present, then it may result in back pain, damage to lungs and heart, etc.
• Risk of falls and injuries in affected individuals with seizures
• Kidney reflux
• Severe learning disabilities
• Severe heart anomalies
• Reduced quality of life

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

How is Chromosome 17p13.3 Microdeletion Syndrome Treated?

There is no cure for Chromosome 17p13.3 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, endocrinologists, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for 17p13.3 Microdeletion Syndrome may involve:

• Use of hearing aids
• 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
• Speech and language therapy; the use of sign language may be beneficial; rectification of hearing impairment may improve speech and language development
• 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)
• Use of walking aids including foot orthotics and special footwear and shoe inserts; wheelchair assistance may be necessary
• 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, as assessed by a healthcare expert
• 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, if necessary
• 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 Chromosome 17p13.3 Microdeletion Syndrome be Prevented?

Chromosome 17p13.3 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) 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 17p13.3 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 17p13.3 Microdeletion Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 17p13.3 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 is generally difficult to predict the long-term outlook.

• Children with mild conditions are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Some children may require lifelong medical support and care. Severe cases of 17p deletions may have unfavorable prognoses

Additional and Relevant Useful Information for Chromosome 17p13.3 Microdeletion Syndrome:

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

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