What are the other Names for this Condition? (Also known as/Synonyms)
What is Chromosome 5q14.3 Deletion Syndrome? (Definition/Background Information)
- Chromosome 5q14.3 Deletion Syndrome is a highly infrequent chromosome abnormality that develops when there is missing genetic material on chromosome 5 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 5 at position q14.3 is missing/deleted
- Some individuals with this deletion may have only mild features, while others may have severe findings that can include growth and developmental delays (speech and motor delays), intellectual disabilities, distinctive facial features, and brain abnormalities
- This chromosomal anomaly is usually known to develop from sporadic mutations (vast majority of cases). 5q14.3 Deletion 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 defects
- The prognosis is primarily dependent on the severity of the disorder, and it varies from one child to another. Many children with Chromosome 5q14.3 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 5q14.3 Deletion Syndrome? (Age and Sex Distribution)
- The incidence of Chromosome 5q14.3 Deletion Syndrome is currently unknown. It is an extremely rare syndrome
- 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
- 5q14.3 Deletion Syndrome is a congenital disorder, and the presentation of symptoms may occur at or following the birth of the child
- 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 5q14.3 Deletion Syndrome? (Predisposing Factors)
In a vast majority of individuals, there are no identified risk factors for Chromosome 5q14.3 Deletion Syndrome.
- In some individuals, a positive family history may be an important risk factor for 5q14.3 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 5q14.3 Deletion Syndrome? (Etiology)
- Chromosome 5q14.3 Deletion Syndrome is caused by a deletion of genetic material in the long arm (q) of chromosome 5. The deletion typically occurs in one of the 2 copies of chromosome 5, and the missing segment corresponds to q14.3
- It is researched that the deletion of the MEF2C gene at this location (q14.3) is responsible many of the significant presentations associated with the syndrome. In some cases, point mutations on the gene may also be contributive
- 5q14.3 Deletion 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 some cases, a microdeletion may take place. 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.
What are the Signs and Symptoms of Chromosome 5q14.3 Deletion Syndrome?
The signs and symptoms of Chromosome 5q14.3 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 associated signs and symptoms depend on what material is lost/missing, how much deletion has occurred (quantity), where the deletions occur, and if the involvement of other chromosomes are noted.
The signs and symptoms of 5q14.3 Deletion Syndrome may vary from one individual to another and may include:
- Developmental delays that may be moderate or severe
- Speech and language delays that are mostly significant; absent or severely delayed speech
- Abnormal facial features that include:
- Small-sized head with broad forehead
- Eyes that are set wide apart; downslanting eyes
- Low-set and unusually-shaped ears
- Prominent nose
- Thin lips
- Cleft palate and palate
- Small and/or receding lower jaw
- Children tend to keep their mouths open
- Short stature
- Low muscle tone (hypotonia) affecting fine motor skills is noted to be usually severe with early-onset
- Feeding difficulties, including gastroesophageal reflux disease (GERD)
- Constipation may be commonly noted
- Mobility issues - children may have unusual movements
- Lack of appetite in children
- Dental problems
- Hand and foot deformities
- Vision and hearing loss are generally mild to moderate; hearing impairment is mostly temporary
- Joint hypermobility is common in children
- Epileptic seizures (and seizure-like movements) that may be of the following types:
- Febrile seizure
- Absence seizure
- Infantile spasm
- Generalized tonic-clonic
- Behavioral issues - decreased social interaction, restlessness,
- Intellectual disability
- Sleep disturbances are commonly noted
- Minor genetic abnormalities, such as cryptorchidism and hypospadias, in boys
How is Chromosome 5q14.3 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 5q14.3 Deletion Syndrome in the differential diagnosis. Often, specialized tests are necessary to confirm the disorder.
5q14.3 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 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 5q14.3 Deletion Syndrome?
The potential complications of Chromosome 5q14.3 Deletion Syndrome may include:
- Severe emotional stress for parents and caregivers
- Pregnancy complications are not commonly seen
- Intrauterine growth retardation (IUGR)
- Delay in achieving developmental milestones such as rolling, crawling, sitting, and walking; many children walk only after age 5 or so
- Head control by the baby/child may develop gradually and slowly and may take till primary school age to gain complete control
- Failure to thrive
- Severe brain anomalies resulting in brain dysfunction from:
- Agenesis of the corpus callosum
- Cerebral atrophy
- Cortical dysplasia
- Delayed myelination
- Enlarged ventricles
- Periventricular heterotopia/leukomalacia
- Social isolation and awkwardness
- Severe learning disabilities; some children are unable to speak
- Reduced quality of life
Complications may occur with or without treatment, and in some cases, due to treatment also.
How is Chromosome 5q14.3 Deletion Syndrome Treated?
There is no cure for Chromosome 5q14.3 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 5q14.3 Deletion 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
- Speech and language therapy; the use of sign language may be beneficial; rectification of hearing impairment may improve speech and language development
- Special education: Employing learning strategies via music therapy, visual and tactile books, learning through fun and play, and lots of repetition. Writing by holding a pencil may be very difficult; but touchscreen computers and keyboards are known to be easier to use and learn
- 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
- A surgical procedure named fundoplication may be necessary in some children with severe gastroesophageal reflux disease (GERD). Milder GERD cases can be generally well-controlled by giving feeds slowly and positioning the baby in a semi-upright position. And, where necessary, raising the head of the end of the bed for sleeping is also recommended
- Surgical correction of physical defects, as assessed by a healthcare expert
- Surgical correction (orchiopexy) of undescended testicles and other genital defects
- 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 5q14.3 Deletion Syndrome be Prevented?
Chromosome 5q14.3 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 5q14.3 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 5q14.3 Deletion Syndrome? (Outcomes/Resolutions)
The prognosis of Chromosome 5q14.3 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
- Some children may require lifelong medical support and care; severe brain abnormalities can worsen the prognosis
- Children with MEF2C gene deletion have generally worser prognosis than those without the gene deletion
Additional and Relevant Useful Information for Chromosome 5q14.3 Deletion Syndrome:
The following DoveMed website link is a useful resource for additional information: