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22q11.2 Deletion Syndrome
Condition Description
Several overlapping syndromes are included in the 22q11.2 deletion syndrome. These include:
- DiGeorge syndrome
- Velocardiofacial syndrome
- Conotruncal anomaly face syndrome
- Some cases of autosomal dominant Opitz G/BBB syndrome
- Sedlackova syndrome
- Cayler cardiofacial syndrome.
Their common genetic cause is a microdeletion (a very small piece of DNA is missing) from the long arm of chromosome 22. All of these conditions have significant overlap in their features and will be treated as a single condition in this brief review. This chromosome deletion is the most common deletion in human beings.
22q11.2 Deletion Syndrome is a contiguous gene deletion syndrome. Contiguous genes are a group of genes that are situated close together along a stretch of a chromosome (a structure in cells made up of DNA and proteins that carries many genes). If this section of the DNA is missing, many genes can be missing which usually causes functional and developmental changes for the person who carries it.
The way 22q11.2 deletion syndrome affects each person can be very different, even when it runs in families. The presence of any one feature (symptom) of the syndrome does not necessarily mean there will be any other feature of the syndrome. The approach to treatment and management of any child with 22q11.2 deletion syndrome must be individualized, to treat their specific features. Most of the time (90%), 22q11.2 deletion syndrome is a one-time event which means that the chances of other family members having or inheriting it is small.
Prevalence
Chromosome 22q11.2 deletion syndrome occurs in approximately 1 out of every 4000 live births and in most cases the patient is the first to have the condition in the family. However, because the number of features and the level of severity can be so different in each person who has it, many investigators believe that the condition is likely more common than these estimates suggest.
22q11.2 deletion syndrome is the second most common cause of developmental delay and major congenital (present at birth) heart disease after Down syndrome. It accounts for approximately 2.4% of people with developmental disabilities and approximately 10% to 15% of people with Tetralogy of Fallot (a type of heart defect). Males and females of all ethnic backgrounds are affected in equal numbers.
Common Associated Conditions
Children with 22q11.2 deletion syndrome often have a subset of some or all of the following features.
- About three quarters (74%) of the time, congenital heart disease will be present. Most commonly, these congenital heart defects are conotruncal defects. This category of heart defects is also known as outflow tract defects and includes tetralogy of Fallot, interrupted aortic arch, ventricular septal defect and truncus arteriosus.
- In 69% of cases, defects of the palate (the roof of the mouth) also occur, especially velopharyngeal incompetence (air leakage through the passage between the back of the mouth and the nasal passages that allows air to escape through the nose during speech), submucosal cleft palate (a split in the soft part of the palate close to the back of the mouth), bifid uvula (a split in the small structure that dangles down at the back of the mouth and is attached to the rear of the soft palate), and cleft palate (a split in the roof of the mouth. A cleft can be in the hard palate, soft palate or both).
- Characteristic facial features often aid in making the diagnosis and include a prominent nose with a rounded tip, smaller than average eye openings, flattened cheek bone areas, a long face, a small chin and a small head.
- Learning difficulties of varying degrees are eventually evident in the majority (between 70% and 90%) of children with 22q11.2 deletion syndrome.
- In addition, the immune system (the system that protects against infectious disease) does not function normally in just over three quarters (77%) of cases, making these children prone to infection.
Other features that may occur less often in some people include:
- Hypocalcemia (low levels of calcium in the blood), which occurs in about half of people with a 22q11.2 deletion. Hypocalcemia may result in seizures.
- Thyroid function may be affected, with either an under active (20% of people) or over active thyroid (5% of people).
- Weakened function of, or unusual structure of the urinary tract (kidneys and bladder working together to remove waste from the body) may be present. These may include a structural urinary tract anomaly (something that is different than expected) in just under a third (31%) of people with the syndrome. In 10% to 11% of children, dysfunctional voiding, unilateral renal agenesis (a missing kidney) or multicystic dysplastic kidneys (kidneys with many cysts that may not function properly) are also present.
Short-Term Treatment and Outcomes
The number and type of associated features will determine the management for each person with 22q11.2 deletion syndrome. Often the first feature noted is a cleft palate (birth defect of the roof of the mouth), which can, along with other factors, complicate feeding. Other common features affecting the digestive tract include acid reflux (stomach acid coming up and irritating the esophagus), dysphagia (difficulty or discomfort swallowing), and constipation (hard stools that make bowel movements difficult). Approximately a third (36%) of children have considerable issues with feeding, some requiring feeding through a tube. A feeding consult may help to identify the best method to assure that enough food is being ingested to support the child's growth.
Developmental delay is often seen in children with 22q11.2 deletion syndrome, including a delay in language. As the child grows older, intellectual disability and learning differences are likely to become more obvious. Verbal IQ is often greater than performance IQ as the child grows. Early intervention services are often helpful in maximizing a child's developmental potential.
Long-Term Treatment and Outcomes
As the child grows, skeletal features such as scoliosis (curvature of the spine) and differences in the shape of the cervical spine may become apparent. Scoliosis develops in almost half (45%) of children with 22q11.2 deletion syndrome, though only a small minority of these children (6%) require corrective surgery.
Developmental delays in language and motor skills may become increasingly evident as a child approaches school age. If a significant intellectual disability is present, special educational services are important to assure that each child develops to his/her fullest potential.
Short stature can also be a part of the syndrome and is sometimes caused by growth hormone deficiency, but not always. Recurrent infections and additional cardiac surgery can impact school attendance.
Implications for Children's Development
Children with 22q11.2 deletion syndrome will usually have developmental delays that include both motor and speech and language areas. Enrollment in Early Intervention services may help to maximize development. Otitis media (inflammation inside the ear) may also result in conductive hearing loss that may increase developmental delays in speech and language. In addition, once speech commences, children with 22q11.2 deletion syndrome often have a hypernasal quality to their speech (nasal sounding). Working with a speech pathologist may help to minimize this tendency.
In general, intelligence scores are shifted lower, with the average IQ in the low 70's. About 30% of children will have an IQ between 80 and 100, which is in the normal range. Memory and rote learning (memorization) is often a strength for these children and this may help them perform better in some school settings, but abstract reasoning (ability to analyze and solve a problem) is often more difficult.
Although a diagnosis of 22q11.2 deletion syndrome presents many challenges for the physical and mental health of the child and his/her family, early diagnosis and consistent support by parents, educators and medical providers can improve and maximize the child's health, development and wellbeing across their life span.