The 22q11.2 deletion occurs in approximately 1 in every 2,000 to 4,000 live births, although this is likely a gross underestimate of its prevalence. It is thought to be almost as common as Down syndrome. In addition, it is the most frequent cause of syndromic palatal defects, and it is found in 1 of 68 children born with a heart defect. Despite this prevalence, many physicians are still not familiar with the diagnosis or its extreme variability. Because of this, a family may search for years for an explanation for a child’s problems, as well as for meaningful help. Sometimes patients are in their late teens or even adulthood when the diagnosis is made, and many people never get properly diagnosed at all.

It is not yet known how common 22q11.2 Duplication is.  Because there are likely so many individuals who remain undiagnosed, it is hard for doctors to estimate the prevalence of this syndrome.  Best estimates fall in the range of 1/700 live births.

There is a lot of confusion about various diagnoses given to children affected by the deletion. Other names that have been used for the 22q11.2 deletion include DiGeorge syndrome, velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome. These are all older names given to a collection of findings by different sub-specialists before anyone knew about the true cause of the various findings – the chromosome 22q11.2 deletion. For example, Angelo DiGeorge, MD, an endocrinologist, focused on problems with calcium; Robert Shprintzen, PhD, a speech pathologist, concentrated on palatal differences; and Dr. Kinouchi and others in Japan looked at heart defects. In 1997, Donna McDonald-McGinn, MS, CGC likened this phenomenon to a group of near-sighted veterinarians trying to describe an elephant by each examining a separate part. Each was accurate in describing his or her own area of interest but none was able to see the big picture; so too was the case of the 22q11.2 deletion prior to the availability of a laboratory test for this chromosomal deletion. We now know that children with velocardiofacial, DiGeorge, conoctruncal anomaly face, Opitz G/BBB, and Cayler cardiofacial syndromes all have the same condition: the 22q11.2 deletion syndrome.

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Today there are many genetic blood tests that can identify the 22q11.2 deletion. They include: FISH (fluorescence in situ hybridization), comparative genomic hybridization (CGH), whole genome or SNP array, and multiplex ligation-probe amplification (MLPA). A routine chromosome study can only identify this very small deletion about 25% of the time, so one of the more specialized tests above needs to be requested in order to detect it.

22q11.2 Duplication Syndrome is not detectable by routine genetic testing (called karyotyping.)  Most individuals with 22q11.2 duplication are identified either by something called array genomic hybridization (array GH) testing or by multiplex ligation-dependent probe amplification (MLPA) testing for 22q11.2 deletion syndrome. Both of these tests are performed with blood work but can be diagnosed in pregnancy using cells from the placenta or the amniotic fluid.

Most times, the deletion is not hereditary or “running in the family,” and parents without the deletion are not at increased risk of having a second affected child. However, a person with the deletion has a 50% chance of passing it on to his or her child with every pregnancy. In addition, as the findings in people with the 22q11.2 deletion are so variable, it is impossible to predict how mildly or significantly affected a child will be. It is important for parents to keep in mind that nothing they did or failed to do could have caused the deletion to occur. It is common for parents to initially feel a sense of guilt over the fact that their child has a "genetic condition,” but it is clear that this was out of their control and not anyone’s fault.

About 70 percent of individuals with the duplication inherit it from one of their parents.  In other cases, the duplication is not inherited and occurs as a random event during the formation of the child.  Any person with the duplication has a 50% chance of having a child with the same duplication. 

Unlike early reports of children with DiGeorge syndrome, many of whom died in early infancy prior to the availability of sophisticated cardiac surgeries and antibiotics to fight infections, the mortality rate in children with the 22q11.2 deletion is very low (~ 4%). Those children who do succumb to problems associated with the deletion often pass away at a very young age (~ 4 months). However, many children and adults have numerous medical problems during their lifetimes that require specialized care. These include:

· Cardiac defects: 75% of children have some type of heart defect, many of whom require surgery to correct the problem, often in the newborn period.

· Developmental delays: Most children (>95%) have motor milestone delays (like walking), delays in emergence of language and specific learning differences requiring special help in school; and a subset of children have autism or autistic like features and/or behavioral differences like ADHD, OCD, anxiety, perseverations, and psychosis. It is important to note that all children benefit from Early Intervention strategies including occupational therapy, physical therapy, and speech therapy, including sign language, in young childhood; this is followed by specific learning style interventions, as most children have relative strengths in reading and rote memorization but more difficulty with math and complex / abstract reasoning (a non-verbal learning disability).

· Palatal differences: 75% of children have differences in their palate allowing milk to come through their nose in infancy (known as nasal regurgitation) and later causing them to have hypernasal speech which makes it difficult for the child to be understood. Here too, many children benefit from surgical interventions, usually performed by a Plastic Surgeon or an ENT as part of a Cleft Palate Team.

 · Endocrine imbalances: Approximately 50% of children have low calcium levels which usually resolve in infancy, but some children require calcium supplements for a longer period of time or during times of illness or stress such as at puberty or post operatively; in addition, some children have trouble with their thyroid (under active or over active) and some have growth hormone deficiency –all of which respond to treatment.

· Hearing loss: Ear infections are common (often due to the high incidence of palatal problems), as is the presence of hearing loss (both conductive and sensorineural), and problems with the child’s airway due to structural differences such as a vascular ring or laryngeal web or associated with reflux. Occasionally a child will have a connection between the wind pipe and feeding pipe (tracheoesophageal fistula) or an abnormal feeding pipe (esophageal atresia). Many children benefit from ear tube placement; some need hearing aides; whereas others require more complex care from an Otolaryngologist. 

· Gastrointestinal and feeding difficulties: Around 35% of children have significant feeding and swallowing problems such as gastroesophageal reflux (GERD) and dysmotility leading to reflux and constipation; less common problems include umbilical hernia, intestinal malrotation, an absent anal opening, Hirshsprung’s disease (where the child has severe constipation/blockage of the bowel), a diaphragmatic hernia where loops of bowel can be in the chest. Most common feeding problems exist in the newborn period and often resolve with medical assistance by school age.

· Blood disorders: Rarely, a child has had problems with bleeding due to the deletion of a gene that codes for clotting on the chromosome with the deletion and a non-working gene on the other chromosome 22 called Bernard-Soullier syndrome and occasionally children have had problems with their blood counts due to an autoimmune problem such Idiopathic Thrombocytopenia and Autoimmune Neutropenia; some children have rarely had a tumor, most notably in the liver (hepatoblastoma) and sometimes elsewhere such as the kidney (Wilm’s tumor, Renal Cell carcinoma) or thyroid; as well as an occasional individual with Leukemia or Lymphoma. With the exception of Bernard-Soullier syndrome, these problems are likely related to the individuals’ “pokey” immune system as well as other genes on other chromosomes that may predispose them to having these problems.

· Immunological and rheumatological issues: 77% of children have immunodeficiency regardless of whether or not they appear to have recurrent infections including things like recurrent infections, not mounting a normal response to vaccines, and not being able to receive live viral vaccines. Most problems resolve in infancy but some older children and adults have chronic infections. In addition, children and adults are more prone to autoimmune diseases such as Juvenile Rheumatoid arthritis, Idiopathic Thrombocytopenia, Autoimmune Neutropenia, Grave’s disease, and Vitiligo.

· Neurological findings: Rarely, children have seizures unrelated to their low calcium levels and/or structural brain differences/a small head. An occasional child will have spina bifida.

· Eye differences: Some children have eye problems such as droopy eyelids (known as ptosis); differences in the whites of their eyes (scleracornea); differences in the colored parts of their eyes (coloboma); and differences with their eye muscles. Some of these problems need surgical treatment or other interventions such as patching of the eyes and others do not.

· Bone troubles: Approximately half of children have differences in the way the vertebrae of the spine are formed at the neck causing decreased room surrounding the spinal cord at the neck in a very small subset of children which often benefit from surgical correction; differences in the bones of the spine in other areas such as the chest (butterfly vertebrae); curvature of the spine (scoliosis); extra ribs, extra fingers and toes; differences in “wing bones (scapula); and occasionally premature fusion of the bones of the skull (craniosynostosis) all of which are able to be helped surgically if needed. Many children also have unexplained leg pain.

· Genito-urinary issues: Around 35% of children have differences in the way their kidneys are formed or how they work such as a single or malformed kidney and/or kidney reflux, as well as, problems with infections, potty training, and differences in the way the genito-urinary system may be formed (hypospadias in boys where the opening of the penis is not at the tip and undescended testes and occasionally an absent uterus in girls); and hernias in the groin.

Ideally, children with the 22q11.2 deletion should receive coordinated care from centers that offer multidisciplinary teams of clinicians, often drawn from more than 20 specialties. Centers address each child’s individual health problems, as well as issues such as speech or learning delays, in order to help these children and their families lead the best life possible.

See our bibliography of medical and professional articles on the 22q11.2 deletion syndrome.

Upon initial diagnosis, the standard assessment and work-up for all ages generally includes:

• Cardiology
• Endocrinology  
• Immunology
• Speech/Language/Developmental Assessments
• A Renal Ultrasound (to check the kidneys)  
• X-rays of the neck (in children old enough to cooperate and where the bones are well ossified – so ~ 3 to 4 years of age)·  
• Deletion studies in both parents when available 

Thereafter, the work-up is individualized, depending on the symptoms, but may include any or all of the following:

• Plastic Surgery/ENT/Audiology  
• Gastroenterology/Feeding Team  
• Hematology  
• Urology/Nephrology  
• Orthopedics  
• Ophthalmology  
• General Surgery  
• Dentistry  
• Rheumatology  
• Neurology/Neurosurgery 
• Psychiatry