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

• 5q Duplication Syndrome
• Partial Trisomy 5q Syndrome
• Trisomy 5q Syndrome

What is Chromosome 5q Duplication Syndrome? (Definition/Background Information)

• Chromosome 5q Duplication Syndrome is a rare chromosomal disorder caused by the presence of an extra copy of a small piece of chromosome 5 in the cells of the body leading to a set of associated signs and symptoms. These may be mild or severe, depending on several factors such as the amount of genetic material gained (duplicated), the number of genes affected, and the function of the affected genes
• The condition affects newborn children (congenital manifestation. Chromosome 5q Duplication Syndrome can result in abnormal facial features, poor motor skills, and many other physical health defects and mental developmental delays. It may present complications such as malnutrition due to feeding difficulties, delayed achievement of milestones, severe heart anomalies, and reduced quality of life
• This chromosomal anomaly may develop from sporadic mutations (vast majority of cases), or it may be inherited from one’s parents (very rarely). 5q Duplication 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 special education, behavior modification, psychotherapy, surgery for correction of physical defects, and growth and development support
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 5q Duplication 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 5q Duplication Syndrome? (Age and Sex Distribution)

• Chromosome 5q Duplication Syndrome is a rare congenital disorder. The presentation of symptoms may occur at birth 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 5q Duplication Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 5q Duplication Syndrome.

• In some individuals, a positive family history may be an important risk factor for 5q Duplication 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 Chromosome 5q Duplication Syndrome? (Etiology)

Chromosome 5q Duplication Syndrome can be caused by:

• A de-novo duplication of genetic material in the long arm (q) of chromosome 5 (majority of cases)
• Heritable changes passed from a parent with Chromosome 5q Duplication Syndrome in which a subsequent chromosomal re-arrangement has led to a balanced translocation (in rare cases)
• If the chromosomal re-arrangement does not result in a net gain or loss of genetic material, it is known as a “balanced translocation”
• Those with balanced translocation of 5q can have abnormalities in the development of egg or sperm, causing the disorder in their offspring
• There are two chromosomes numbered 5. Children with 5q Duplication Syndrome typically will have one (chromosome 5) in normal condition, while the other is abnormal. The abnormality is characterized by a gain of chromosomal material
• The type of duplications may be termed proximal (when the additional material added is closer to the center of the chromosome) or distal (when the genetic material added is closer to the tip of the chromosome). When only a tiny portion of the genetic material is missing, it is termed as a microduplication
• Other forms of deletions that are known to take place include terminal deletions (denoted as “qter”), when the tip/end of the chromosome is lost; and interstitial deletions, where a certain length of the long arm of chromosome is missing, but the tip/end is still present. The signs and symptoms may vary considerably based on the location of the addition
• Based on the type of duplications i.e., whether distal, proximal, interstitial, or terminal, 5q duplications have been categorized into the following groups:
  • Category A - 5q11 to 5q22 proximal duplications
  • Category B - 5q31 to 5qter distal duplications
  • Category C - 5q34 to 5qter distal duplications
• It is observed that when the duplication of material occurs at the tip of the chromosome, the conditions are generally mild. In severe cases, where large duplications are noted (or the centromere, present in the middle portion of the chromosome, is involved), the child may be severely 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.

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

What are the Signs and Symptoms of Chromosome 5q Duplication Syndrome?

The signs and symptoms of Chromosome 5q Duplication 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. As a general rule, a small gain in chromosome material generally results in milder signs and symptoms. Conversely, larger gains/duplications 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 gains, may have disproportionately severe presentations.

The associated signs and symptoms depend on what material is duplicated, how much duplication has occurred (quantity), where the duplications occurs (such as at the tip or center of the chromosome), and if the involvement of other chromosomes are noted.

The commonly noted signs and symptoms of Chromosome 5q Duplication Syndrome may include:

• Global developmental delays
• Poor muscle tone
• Feeding difficulties due to swallowing difficulties, vomiting, and gastroesophageal reflux disease
• Presence of abnormal hands and feet, including loose joints and joint pain
• Distinctive facial features including large or small sized head
• Epileptic seizures
• Speech and learning disabilities that may be mild, moderate, or severe
• Congenital heart defects
• Minor genital abnormalities
• Umbilical and inguinal hernias
• Intellectual disability
• Sleep disturbances that can affect one’s physical and mental health
• Behavioral problems that include autism, communication difficulties, and social awkwardness
• Dental abnormalities
• Hearing and vision impairment

How is Chromosome 5q Duplication 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 5q Deletions in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 5q Duplication 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.
• Hearing assessment through various tests including:
  • Otoscopy: Examination using an instrument that allows the physician to look inside the ear
  • Weber test: A test in which a vibrating tuning fork is placed on the midline of the head
  • Rinne test: A test in which a vibrating tuning fork is held next to the ear and then in front of the ear, until the individual no longer hears the sound
  • Audiometric test: Hearing tests that involve listening to different tones
  • Tympanometry: A test that puts air pressure in the ear canal in order to move the eardrum, and then measures the eardrum mobility (movement)
• Eye and vision assessment through:
  • General eye exam
  • Visual acuity test using a special and standardized test chart (Snellen chart)
  • Refraction studies using various instruments
  • Alignment and focusing testing
  • Fundoscopic (ophthalmoscopic) examination by an eye specialist, who examines the back part of the eye (or the fundus)
  • Slit-lamp examination
  • Visual evoked potential (VEP) test
  • Fundus fluorescein angiography
  • Optical coherence tomography (OCT) of eye
• Evaluation of heart defects through:
  • Chest X-rays
  • Echocardiogram
  • Electrocardiogram (EKG)
  • Cardiac catheterization
  • Fetal ultrasound for heart defects
• Radiological studies of the affected regions, as needed
• Kidney and urinary tract scans
• 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 Chromosome 5q Duplication Syndrome?

The complications of Chromosome 5q Duplication Syndrome may include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR)
• Failure to thrive
• Delayed milestone achievement that may affect when a child rolls, sits, crawls, or walks
• Poor growth due to malnutrition caused by weak suckling
• Spinal curvature abnormalities
• Severe intellectual deficiency (low IQ levels)
• Risk of falls and injury due to seizures
• Hearing loss and vision loss
• Frequent ear and respiratory infections
• Infertility
• Inappropriate or violent behavior
• Physical abnormalities that can cause difficulties in day-to-day living
• Reduced quality of life

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

How is Chromosome 5q Duplication Syndrome Treated?

There is no cure for Chromosome 5q Duplication 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 Chromosome 5q Duplication Syndrome may involve:

• Use of hearing aids, as needed
• 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 suitable learning strategies via music therapy, visual and tactile books, learning through fun and play, and lots of repetition. 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; 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)
• 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
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time without any invasive procedures
• 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
• 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
• Social skills training support groups and exercises
• Occupational therapy

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

How can Chromosome 5q Duplication Syndrome be Prevented?

Chromosome 5q Duplication 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 5q Duplication 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 5q Duplication Syndrome? (Outcomes/Resolutions)

• The prognosis of Chromosome 5q Duplication 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
• Some of the abnormalities involving the heart, seizures, recurrent infections, motor skills, communication and behavioral issues are generally known to resolve or improve with time
• In some cases, children may need lifelong medical support and care; it may also take them a long time (several years) to gain a measure of independence

Additional and Relevant Useful Information for Chromosome 5q Duplication Syndrome:

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

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