22q FAQ:

The deletion occurs in an estimated 1 in 2,000-4,000 live births, although this is possibly an underestimate of the prevalence of this deletion, making it almost as common as Down syndrome and impacting approximately 150,000 individuals in the U.S. alone. 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. 22q11.2DS is the most common microdeletion syndrome and it is the leading genetic cause of schizophrenia. Despite this prevalence, many physicians are still not familiar with the diagnosis or its extreme variability. Because of this, a family may search several years for an explanation for the child’s problems, as well as for meaningful help. Sometimes patients are in their late teens or even adulthood before the diagnosis is made. 

Other names for the 22q11.2DS include DiGeorge syndrome, Velo Cardio Facial syndrome, conotruncal anomaly face syndrome, and Cayler Cardiofacial syndrome. These were all names given to a collection of findings by different sub-specialists before anyone knew about the true etiology of the various findings – the chromosome 22q11.2 deletion. For example, Angelo DiGeorge, MD, was focusing on the immunodeficiency; Robert Shprintzen, PhD, a Speech Pathologist, was concentrating on palatal differences; and Dr. Kinouchi and others in Japan were looking 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 in l994 of a laboratory test for this chromosomal deletion.  Although there has been an effort to streamline the name of this syndrome to just 22q11.2 Deletion Syndrome, DiGeorge Syndrome or Velo Cardio Facial Syndrome are names still commonly in use in different locations.  However, it is important to understand that the underlying issue in all of these cases is the deletion and that the research and information published is applicable across the board. 

Today there are many tests that can identify the deletion, and they are most readily performed as blood tests. They include FISH (fluorescence in situ hybridization), array-comparative genomic hybridization (CGH)/microarray, whole genome or SNP array, and multiplex ligation-probe amplification (MLPA). In general, a regular chromosome study will not identify this very small deletion, e so one of the above more specialized tests would need to be requested in order to find the deletion.

There are also tests available currently to detect the deletion prenatally.  Fetal ultrasound is useful in identifying heart defects or major structural anomalies that may signal the need for more tests, but many children with the 22q11.2 deletion do not have major structural issues that would show up on routine ultrasound.  New non-invasive prenatal tests (NIPTs) are now available to detect the deletion with high accuracy, but they are still under study for their efficacy.  More invasive tests include chorionic villus sampling or amniocentesis utilizing FISH or microarray technology are options, especially for those with pregnancies at  risk for the syndrome. 

22q11.2DS is a genetic condition, but it is not always inherited.   Approximately 93% of the time this deletion occurs as a chance event during the early development of the fetus or in the formation of egg and sperm cells. Approximately 7% of the time, this condition is inherited from an affected parent. 22q11.2DS is inherited in an autosomal dominant pattern.    Once it is present the person with the deletion has a 50% chance of passing it on to his or her child. It is important to know that the eggs and sperm have no memory, so every pregnancy has the same 50% chance of having a child with the deletion even if there is an affected child already in the family. In addition, as the findings in people with 22q11.2DS are variable it is impossible to predict how mildly or significantly affected a child will be.  There is some evidence that second generation children may be more severely impacted.

When neither parent is affected, it is a de novo or brand new occurence in their child.It is nothing that the parents did or did not do that caused it to occur. It occurs on a very cellular level due to the inherent structure of the chromosome and it is nothing that anyone has any control over. This is very important as many families feel a sense of guilt over the fact that their child has a “genetic condition” but this is not anyone’s fault.  Currently there is no evidence to explain why the deletion occurs or knowledge as to how it can be prevented. 

22q11.2 deletion syndrome impacts each individual differently.  Some are more affected with many more medical problems than others.  For example, a number of children have congenital heart defects (about 60%) while others have no heart issues at all.  Some have unintelligible speech that requires corrective surgery, while others have normal speech patterns.  This wide variability is one of the reasons that this syndrome is so elusive.  However, when a child presents with several of the typical 22q11.2DS, it should raise a red flag and trigger genetic testing to confirm a diagnosis.  There are many reasons why just one of the following issues would be present in a young child, but when several symptoms are present it is important to investigate further for an underlying cause. 

Most typical symptoms: 

• Cardio-vascular anomalies
• Cleft palate
• Feeding difficulties
• Immune system problems
• Developmental delay (meeting milestones later)
• Significant learning difficulties (especially in math and reading comprehension)
• Speech problems (usually hyper nasal speech)
• Delayed social emotional development
• Mental health/behavioral difficulties (anxiety, ADHD, executive functioning deficits, etc.)
• Renal abnormalities
• Growth hormone deficiencies

There are over 180 different features associated with this syndrome. A more comprehensive list of issues is below:

Cognitive/learning

• Learning difficulties (math concepts, reading comprehension)
• Concrete thinking, difficulty with abstract thinking
• Communication difficulties
• Borderline normal intellect as child reaches adulthood
  • Difficulties with attention and focus (primarily inattention)
• Poor adaptive skill development
• Difficulty generalizing learned information

Vascular anomalies

• Medially displaced internal carotid artery
• Tortuous, kinked, absent or accessory internal carotids
• Jugular vein anomalies
• Small veins
• Circle of Willis anomalies
• Absence of vertebral artery (unilateral)
• Low bifurcation of common carotid
• Tortuous or kinked vertebral arteries
• Raynaud’s phenomenon
• Thrombocytopenia, Bernard-Soulier disease

Unlike the early reports on children with the 22q11.2 deletion 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 22q11.2DS is very low (~ 4%). However, many children and adults have numerous medical problems across their lifetime that require specialized care.  

The 22q11.2 Society created and upated set of managing guidelines for patients with 22q11.2 deletion syndrome, coordinating a global effort of expert clinicians and incorporating input from patient advocacy groups. This update involved a systematic literature review and the creation of a multidisciplinary consensus document for both children and adults that are necessary for physicians to follow. 

Links to those documents and other articles can be found here: 

• Practical guidelines for managing patients with 22q11.2 deletion syndrome (children)
• Practical guidelines for managing adults with 22q11.2 deletion syndrome
• Speech-Language Disorders in 22q11.2 Deletion Syndrome: Best Practices for Diagnosis and Management

Below are some statistics and general care guidelines:

• Cardiology – 60-75% of children with 22qDS have some type of heart defect, many of whom require surgery to correct the problem, often in the newborn period.
• Child Development – Almost all children (>95%) have milestone delays in areas such as fine and gross motor skills, speech/language skills, and learning. A subset of children has autism or autistic like features. Almost all children with 22qDS need and will benefit from early intervention strategies such as occupational therapy, physical therapy, speech therapy and cognitive developmental stimulation.
• Cleft Palate Team – Over 75% of children have differences in their palate (usually a submucosal cleft palate with velopharyngeal insufficiency) and/or language delays. These issues require careful monitoring by an ENT for possible surgery and intervention by a speech and language pathologist. Many young children with 22qDS have speech that is difficult to understand and that has a nasal quality. Their language acquisition can be slow to develop, and they may have both expressive and receptive delays. Surgery to correct the palate and improve intelligibility can be quite successful when followed by targeted speech therapy. Language deficits can also be improved substantially with therapy interventions.
• Endocrinology – 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.
• ENT and Audiology – 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 windpipe and feeding pipe (tracheoesophageal fistula) or an abnormal feeding pipe (esophageal atresia). Many children benefit from ear tube placement; some need hearing aids; and others require more complex care from an Otolaryngologist.
• Gastroenterology/Feeding Team – 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. However, there are a fair number of children who are put on feeding tubes to their early years to maintain adequate growth and nutrition.
• Hematology/Oncology – A small number of children have 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. There is some evidence emerging for increased cancer risk in this population, but further studies in this area are needed.
• Immunology/Rheumatology – Over 70% of children have some type of immunodeficiency and are prone to recurrent infections, and vaccine response abnormalities. Many problems resolve in infancy, but some older children and adults have chronic infections and ongoing issues. 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.
• Neurology – Some children and adults develop seizures unrelated to their low calcium levels. There is emerging evidence of a possible link to Parkinson’s Disease in some older adults, but more studies need to be conducted in this age category.
• Ophthalmology – Many children have structural 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. There have also been reported cases in young adults of keratoconus (cornea disease). Some of these problems need surgical treatment or other interventions such as patching of the eyes and others do not. Visual processing difficulties are very common in the syndrome and these difficulties can interfere with learning. Among the areas that are impacted are visual form constancy, visual sequential memory and visual closure.
• Orthopedics – Some issues related to the syndrome are differences in the bones of the spine and 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.
• Psychiatry – Many children have mental and behavioral health challenges such as ADHD, OCD, anxiety, and perseveration. There is a higher risk for psychotic disorders into adulthood.
• Urology – About 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 genital-urinary system may be formed. Some issues occasionally occurring are hypospadias in boys (where the opening of the penis is not at the tip). undescended testes, occasionally an absent uterus in girls, and hernias in the groin.

Ideally, children with the 22q11.2 deletion receive coordinated care in centers comprised of multidisciplinary teams of clinicians often drawn from more than 20 specialties. A multipronged approach encourages discussion among many specialty providers and case management for families. 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. Some families find it helpful to petition health insurance to cover travel to a specialty clinic that has experience with this syndrome. In the United States several clinics exist that would be able to evaluate and give guidance to primary care providers who may be less familiar with the syndrome. A list of clinics that specialize in this syndrome can be found under the tab Living with 22q.

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

• Genetics
• Cardiology
• Endocrinology
• Immunology
• Speech/Language
• Audiology
• Neurology
• Developmental Behavioral Pediatrics/Psychology

As well as:

• 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 around 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 the following:

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

Most children and adults with the 22q11.2 deletion do quite well both medically and as members of their families and communities at large. As with anything that is unexpected, coming to terms with the diagnosis is often difficult at first, but becomes easier as more information becomes available and as families have an opportunity to meet other children and adults with the 22q11.2 deletion and/ or to converse with them through diagnosis specific internet sites. In addition, attendance at family meetings/picnics; contacting support networks; and sending children to camps specifically designed for those individuals with a 22q11.2 deletion such as Dragonfly Forest (www.dragonflyforest.org) is often helpful as families realize they are not alone. 

Given the rapid advancement of genome studies and a heightened interest in this particular syndrome, there is every reason to be optimistic as newer and better treatments are on the horizon.  Multiple research sites around the world are in the process testing new approaches to treatment and there is growing understanding of the mechanisms that are causing the health difficulties.  Parents are encouraged to focus on their specific child’s needs and not to worry about problems that may occur in the future.  It is very difficult to predict the future, so a proactive, educated approach may offer the best chance for a positive long-term outcome. 

Also the power of community is huge in helping families find a new sense of comfort.  Be sure to visit our Events page to learn more about virtual and in-person opportunities to connect.