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

• 18q Deletions from 18q21 and beyond

What is Chromosome 18q Deletions from 18q21 and beyond? (Definition/Background Information)

• Chromosome 18q Deletions from 18q21 and beyond is a chromosome abnormality that affects many different parts of the body. Individuals with this condition are missing genetic material located on the long arm (q) of chromosome 18, in the region from 18q21 and beyond. 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
• Most cases of 18q Deletions from 18q21 and beyond are not inherited, although affected individuals can pass the deletion on to their children. Common features observed in individuals with this deletion include some abnormal craniofacial features, poor muscle tone, seizures, and growth and developmental delays
• Following a diagnosis of Chromosome 18q Deletions from 18q21 and beyond, 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 seizure control, speech and language therapy, physiotherapy, and surgery for correction of physical defects, if any
• The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 18q Deletions from 18q21 and beyond are able to cope well through adequate treatment and supportive care

Who gets Chromosome 18q Deletions from 18q21 and beyond? (Age and Sex Distribution)

• Chromosome 18q Deletions from 18q21 and beyond is a rare congenital disorder. 18q deletions are generally uncommon and according to literature the incidence is about 1 in 40,000 live births
• 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 18q Deletions from 18q21 and beyond? (Predisposing Factors)

In a vast majority of individuals, there are no identified risk factors for Chromosome 18q Deletions from 18q21 and beyond.

• A positive family history may be an important risk factor since 18q Deletions from 18q21 and beyond 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 18q Deletions from 18q21 and beyond? (Etiology)

Chromosome 18q Deletions from 18q21 and beyond are caused by the deletion of genetic material from chromosome 18. The amount of missing chromosome material varies widely from one individual to another resulting in a variable set of signs and symptoms. There are two types of deletions recorded in the medical literature.

• Interstitial deletion: Here, there is a loss of chromosomal material from between the 18q21 region to the end of the chromosome 18 on its long arm (q). The term “interstitial” means that the chromosome material on the q arm broke at two locations (between 18q21 and end of the chromosome) and the broken ends have joined together; and, the broken segment after 18q21 is lost or missing
• Terminal deletion: Here, there is breakage of chromosome 18 at a single point beyond the q21 region, and the chromosome material till the end of the q arm is lost/missing (the broken piece gets detached and is lost)
• The severity of the condition and the associated signs and symptoms vary depending on the size of the deletion (whether small or large), the breakpoints involved, and the genes that are affected/lost
• Most cases of the disorder develop sporadically (de novo) during embryonic development. This means that no deletion of genetic material at 18q is observed in either of the parents. However, in rare cases, the disorder may be inherited

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 18q Deletions from 18q21 and beyond?

The signs and symptoms of Chromosome 18q Deletions from 18q21 and beyond 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 18q Deletions from 18q21 and beyond include:

• Growth and developmental delays
• Short stature (mostly arising from growth hormone deficiency)
• Speech, language, and learning difficulties that may be mild to moderate
• Hypotonia (reduced muscle tone) resulting in a soft and floppy body of the infant
• Feeding difficulties; sucking and swallowing may be difficult
• Poor fine motor skills in some children; the hand eye coordination may be weak
• Seizures may be seen in between 10-30% of the infant children
• Minor genital abnormalities, particularly in boys (some girls are also affected)
• Hand and feet abnormalities (mostly foot problems such as rocker bottom feet and high-arched heels)
• Children may have a variety of allergies including asthma
• Eczema
• Umbilical hernia may be noted in over 40% of the affected children
• Heart defects may be noted in between 25-35% of the children
• Craniofacial features may be slightly different from other children and include:
  • Small head size and midface hypoplasia
  • Eyes set widely apart with small openings between the eyelids; the eyes may be downturned or upturned at the corners
  • Low-set ears
  • Cleft lip and palate
• Hearing and vision may be affected; some present narrow ear canals and frequent ear infections
• Behavioral issues

How is Chromosome 18q Deletions from 18q21 and beyond 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 18q Deletions from 18q21 and beyond in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.

Chromosome 18q Deletions from 18q21 and beyond 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
• Assessment of hearing and vision of the affected child
• 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 18q Deletions from 18q21 and beyond?

The complications of Chromosome 18q Deletions from 18q21 and beyond may rarely include:

• Severe emotional stress for parents and caregivers
• Pregnancy complications
• Intrauterine growth retardation (IUGR)
• Delayed milestone achievement
• Thyroid gland abnormalities
• Hearing loss
• Brain abnormalities (in rare cases) including delayed myelination
• Rheumatoid arthritis may be occasionally noted
• Recurrent infections due to poor immunity
• Kidney defects such as kidney reflux
• Behavioral issues, such as hyperactivity, temper tantrums, and aggression, may be observed
• Reduced quality of life

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

How is Chromosome 18q Deletions from 18q21 and beyond Treated?

There is no cure for Chromosome 18q Deletions from 18q21 and beyond 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, otolaryngologists, neurologists, internists, cardiologists, endocrinologists, surgeons, and other healthcare professionals are involved in managing the condition.

The treatment measures for Chromosome 18q Deletions from 18q21 and beyond may involve:

• Use of hearing aids
• Use of vision aids
• 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
• Employing learning strategies via music therapy, visual and tactile books, learning through fun and play, and lots of repetition
• Speech and language therapy; the use of sign language may be beneficial; rectification of hearing impairment may improve speech and language development
• Seizure control using anticonvulsant medication, vitamin supplements, and ketogenic diet
• 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)
• Surgical correction of physical defects, as assessed by a healthcare expert
• Surgical correction (orchiopexy) of undescended testicles and other genital defects
• 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 18q Deletions from 18q21 and beyond be Prevented?

Chromosome 18q Deletions from 18q21 and beyond 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 18q deletions 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 18q Deletions from 18q21 and beyond? (Outcomes/Resolutions)

The long-term outlook (prognosis) for people with Chromosome 18q Deletions from 18q21 and beyond varies from one individual to another.

• The severity of the condition and the associated signs and symptoms largely depend on the size of the deletion, the breakpoints, and the genes involved
• Weak muscle tone (hypotonia) severity may determine motor function delays; it improves with physiotherapy and as the child gets older
• Occasionally, children may require lifelong medical support and care

Additional and Relevant Useful Information for Chromosome 18q Deletions from 18q21 and beyond:

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

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