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

• 6q Deletion Syndrome
• 6q Monosomy Syndrome
• Partial Monosomy 6q Syndrome

What is Chromosome 6q Deletion Syndrome? (Definition/Background Information)

• Chromosome 6q Deletion Syndrome is a rare chromosomal disorder that develops when there is missing genetic material on chromosome 6 (on long arm q) 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 lost, the number of genes affected, and the function of the affected genes
• The signs and symptoms observed in individuals with Chromosome 6q Deletion Syndrome include developmental delay, feeding issues, behavioral problems, cognitive disability, and hearing and vision abnormalities. This chromosomal anomaly may develop from sporadic mutations (majority of cases), or it may be inherited from one’s parents (in rare cases)
• Chromosome 6q Deletion Syndrome may be diagnosed through specialized genetic testing. In some children, the condition may be mild and hence can also remain undiagnosed. The treatment of 6q Deletion Syndrome is based on the signs and symptoms present in each individual
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 6q Deletion 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 6q Deletion Syndrome? (Age and Sex Distribution)

• Chromosome 6q Deletion 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 6q Deletion Syndrome? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 6q Deletion Syndrome.

• In some individuals, a positive family history may be an important risk factor for 6q Deletion 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 6q Deletion Syndrome? (Etiology)

Chromosome 6q Deletion Syndrome may be caused by:

• De-novo deletion of genetic material from the long arm (q) of chromosome 6 (most frequent)
• Inheritance of chromosome 6q deletion (in rare cases)

There are two chromosomes numbered 6. Children with Chromosome 6q Deletions typically will have one (chromosome 6) in normal condition, while the other is abnormal. The abnormality is characterized by a loss of chromosomal material.

According to literature, the following different syndromes are recognized based on the specific 6q band involved:

• 6q Deletions 6q11 to 6q16
• 6q Deletions 6q13 to 6q14
• 6q Deletions 6q15 to 6q23
• 6q Deletions from 6q23 to 6q24
• 6q Deletions from 6q25
• 6q Deletions from 6q26 and 6q27

The severity of the condition and the associated signs and symptoms vary based on the size of the deletion and the genes that are involved.

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 6q Deletion Syndrome?

The signs and symptoms of Chromosome 6q Deletion 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 6q Deletion Syndrome include:

• Feeding difficulties due to swallowing difficulties, vomiting, and gastroesophageal reflux disease
• Hearing impairment
• Vision defects
• Small hands and feet
• Poor muscle tone (hypotonia) causing motor delays that can be mild or severe
• Poor fine motor skills that indicate one’s hand-eye coordination may be severely affected
• Difficulty in climbing stairs and difficulty in sitting without support
• Standing and walking difficulties
• Seizures
• Speech and learning disabilities
• Developmental delays
• Distinctive facial features may include small-sized head, large forehead, flat nose, low-set ears, eyes set inside deep sockets, and cleft lip and palate
• Underdeveloped genitalia, especially in boys, and undescended testes
• Sleep disturbances that can affect one’s physical and mental health
• Behavioral problems

How is Chromosome 6q Deletion 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 6q Deletion Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 6q Deletion 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 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
• 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 6q Deletion Syndrome?

The complications of Chromosome 6q Deletion Syndrome may include:

• Severe emotional stress for parents and caregivers
• Delayed milestone achievement
• Vision loss; cortical visual impairment resulting in partial or total blindness
• Poor growth due to malnutrition caused by weak suckling
• Short stature
• Spinal curve abnormalities, such as scoliosis and kyphosis, which mostly develops from hypotonia
• Thyroid dysfunction leading to hypothyroidism
• Kidney defects such as kidney stones and single kidney
• Severe intellectual deficiency
• Inappropriate or violent behavior
• Physical abnormalities that can cause difficulties in day-to-day living

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

How is Chromosome 6q Deletion Syndrome Treated?

There is no cure for Chromosome 6q Deletion 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 6q Deletion Syndrome may involve:

• Use of hearing aids and cochlear implants; 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. A surgical procedure named fundoplication may be necessary in some children with severe GERD
• Severe constipation may require dietary changes, including increased intake of fiber and wholegrains, along-with the administration of laxatives
• Heart abnormalities may require surgical correction in some cases; some defects tend to improve over time, sometimes within a year
• 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
• 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

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

How can Chromosome 6q Deletion Syndrome be Prevented?

Chromosome 6q Deletion 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 6q Deletion 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 6q Deletion Syndrome? (Outcomes/Resolutions)

The prognosis of Chromosome 6q Deletion 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

• Children with mild conditions (usually from small deletions) are generally able to cope well via appropriate treatment and adaptive behaviors as they get older
• Weak muscle tone severity may determine motor function delays; it improves with physiotherapy and as the child gets older
• In some cases, lifelong medical support and care may be necessary

Additional and Relevant Useful Information for Chromosome 6q Deletion Syndrome:

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

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