Definitions

• What is Autism?

• What is Velocardiofacial Syndrome (VCFS)?

• Frequently Asked Questions

What is Autism?

Autism is a complex developmental disability that typically appears during the first three years of life and leads to unusual interests or repetitive behaviors, and problems with communication and social relationships.  The result of a neurological disorder that affects the functioning of the brain, autism and its associated behaviors have been estimated to occur in as many as 2 to 6 in every 1.000 individuals (Centers for Disease Control and Prevention 2001).  It is four times more likely to occur in boys than in girls and knows no racial, ethnic, or social boundaries.  Family income, lifestyle, and educational levels do not affect the chance of autism’s occurrence.  At this time, exactly what causes the abnormal brain development is unknown.

Because autism is a spectrum disorder, individuals may be severely affected or only mildly impaired.  The symptoms and characteristics of autism can present in a wide variety of combinations.  Two children, both with the same diagnosis, can act very differently from each other and have varying strengths and challenges.

Every person with autism is an individual, and like all individuals, has a unique personality and combination of characteristics. Some common characteristics of autism are:

• Insistence on sameness; resistance to change
• Uneven gross and fine motor skills
• Repeating words or phrases in place of normal, responsive language
• Laughing, crying, showing distress for reasons not apparent to others
• May not want to cuddle or be cuddled
• Difficulty in mixing with others; prefers to be alone
• Little or no eye contact
• Unresponsive to normal teaching methods
• Sustained odd play—spins objects
• Over sensitivity or under sensitivity to pain
• No real fear of danger
• Not responsive to verbal cues; acts as if deaf although hearing tests in normal range
• Noticeable physical over-activity or extreme under-activity

There are many different behavioral, educational, dietary and pharmacological treatments for autism. Few of these treatments have been well studied and most seem to work for only a subset of people.  However, most clinicians and researchers think early, intensive intervention while the brain is still developing is important in the treatment of those with autism.                            

Autism Resouces (links):

• National Alliance for Autism Research & Autism Speaks
• Autism Society of America
• Other Autism Resources
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What is Velocardiofacial Syndrome (VCFS) or 22q11 Deletion Syndrome?

22q11deletion syndrome (22qDS) is a genetic disorder caused by a small deletion of part of chromosome 22. 22qDS is closely related to several other syndromes, and it has been called by many names.  For example, it is also referred to as velocardiofacial syndrome (VCFS), DiGeorge sequence, Shprintzen syndrome, Robin sequence, CATCH 22 (Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcaemia), or conotruncal anomaly face syndrome (CTAF).  A large percentage of people with DiGeorge syndrome, Robin sequence, or the other named disorders above have a chromosome 22q11 deletion.  However, not everyone with 22qDS meets the clinical criteria for the other named syndromes (like DiGeorge syndrome or Shprintzen syndrome).  Therefore, we will refer to the disorder as 22qDS meaning that an affected person is missing a specific part of chromosome 22.

How common is 22q11 deletion syndrome?

About 1 in every 4000 people are born missing part of chromosome 22, but its effects on each person are unique.  Many people with 22qDS will have some form of a birth defect.  Often the heart and roof of the mouth (known as the palate) are affected.  The face and the brain may also develop differently from most people.  In addition, a small number of people also have malformations of their skeleton, urinary system, and immune system.  Some also have problems regulating the level of calcium in their blood.  However, the specific types of malformations or developmental differences and their severity are highly variable. 

What types of problems does 22qDS cause? 

The most common abnormalities in people with 22qDS are heart defects – over half (between 50 and 80 percent) have some form of heart defect.  These heart defects are of several different types, including conotruncal heart anomalies (10-30%) such as interrupted aortic arch type II (14%), ventricular septal defect (14%) and truncus arteriosus (9%).  Although there are many causes of heart defects, about 3% of people with congenital heart problems have 22qDS.

Birth defects of the face, or subtle differences in the proportion or shape of the face (known as “minor anomalies”) are also common with 22qDS.  Problems with the palate and the way it connects with the back of the throat, known as velopharyngeal insufficiency (VPI), are also common.  About one in eight people with 22qDS have a cleft palate without a cleft lip.  In fact, 22qDS is found to be the cause of cleft palate in many people (around 1 in 8) who have cleft palate without a cleft lip.  VPI and hypernasal speech (often related to VPI) are seen in at least a third of people with 22qDS. It is thought that more than half of people with VPI have 22qDS.

Learning problems or disabilities are also commonly found among people with 22qDS.  In young children, language problems are often seen and, in older children, problems with nonverbal tasks such as math or handwriting are more common.  Many people with 22qDS also develop emotional problems or mental illnesses.  Young children often seem very anxious.  Adolescents and adults frequently develop serious psychiatric illnesses including depression, bipolar disease and schizophrenia.  The exact rates of these psychiatric problems are unclear but estimates go as high as 40% for any mental illness, 30% for a mental illness that causes serious problems with one’s perceptions and beliefs (known as psychosis) and 25% for a specific type of mental illness associated with psychosis (schizophrenia).  It appears that approxiately 2-5% of people with schizophrenia have 22qDS.

It is important to realize that none of the numbers above are exact because the people with 22qDS who have helped doctors in learning more about the deletion have usually had serious medical problems that first led them to start working with the doctors.  It is possible that there are other people with 22qDS that the doctors and researchers don’t know very much about because they don’t have serious medical problems. 

Why do people with 22qDS have these problems?

People think that 22qDS causes all of these different problems because the missing genes affect how many different parts of the body develop.  This is especially important before the affected person is born since all parts of the body are developing then.  In addition, the deletion may continue to influence the development of parts of the body that change as one gets older.  The brain is probably the part of the body that changes most throughout our lives.  This might be why some of the learning and emotional difficulties that people with 22qDS experience might not be present until they get older.  Research looking at the size and shape of the brains of people with 22qDS have found greater changes in the brains of older children than younger children.  This suggests that the effect of the deletion might be different at different ages.  Recent studies have found that only certain parts of the brain are affected by the deletion.  Other studies have found that the brain changes caused by the deletion might be different depending upon whether the missing genetic material was from the mother or the father.  This is important because sometimes only genes that come from the mother are turned on and in other cases, only genes that come from the father are turned on.

Our research group is especially interested in learning more about the brain changes that are sometimes seen in 22qDS.  One of the first things we want to understand is why some people with 22qDS have thinking and behavioral problems and why some do not.  We are trying to find out if there are any characteristics that can be identified early on, that make it more likely that someone with 22qDS will develop emotional or behavioral problems when they are older.   We also want to know if there are things that happen (like stress or using certain kinds of medications or drugs) that make it more or less likely that a person will develop these kinds of problems as they get older.  We hope that understanding these factors may help in finding new ways to keep 22qDS patients healthy. 

Frequently Asked Questions:

The exact cause of 22qDS is unknown.  What we do know is that it is a genetic disorder, in which a small part of chromosome 22 is missing.  The part that is most commonly missing contains about 30 genes.  However, we do not yet understand the function of these genes, nor how they are involved in causing 22qDS.  Chromosomes are threadlike structures that are found in every cell of the body and house the body’s genes.  A human cell normally contains 46 chromosomes (23 from each parent) and each chromosome contains hundreds of genes.  As a result of the deletion in chromosome 22, some of the genes are absent from this chromosome.  These missing genes may be responsible for some of the abnormalities associated with 22qDS.  It is possible that mistakes are made copying this part of chromosome 22 during development because the DNA there is very repetitive. 

2. Why are there so many names for 22qDS?

22qDS is thought to be the underlying cause of the medical problems associated with the vast majority of patients with VCFS, DiGeorge syndrome, CTAF, and Robin sequence.  In fact, all DiGeorge, CTAF, Robin patients with a deletion in chromosome 22 have 22qDS; however, not everyone with 22qDS will meet the clinical criteria for the other named syndromes. Furthermore, the diagnostic name given to a particular patient’s set of findings is generally determined by the subspecialist whom the patient first sees.  For example, many patients diagnosed with CTAF first saw a cardiologist because of their heart defect.  The same is true for many patients with DiGeorge syndrome who often have problems with calcium and their thymus gland in addition to their heart problems.  Patients diagnosed with VCFS usually are first seen at craniofacial clinics due to a cleft palate or velopharyngeal insufficiency.  Thus, the perception that these diagnoses were distinct disorders may ultimately be explained by the bias of each medical group’s area of expertise.   These symptomatic descriptions, such as DiGeorge, Robin, and CTAF are all secondary sequences that are etiologically heterogeneous, whereas 22qDS has only been related to 22q11.2 deletions and no other cause has yet been isolated.  Thus, we refer to all disorders related that deletion in chromosome 22 as 22qDS. 

3. What are the chances of having a child with 22qDS?

Although 22qDS is a genetic disease, most cases are thought to be “spontaneous”, meaning that they are not passed down from generation to generation (like freckles or eye color).  In these cases, a “mistake” is made in copying chromosome 22, and these mistakes are not predictable.  In a few cases, however, a deleted copy of chromosome 22 is inherited from a parent who also has 22qDS – this appears to happen for about 10% to 15% of all cases of 22qDS.  If neither parent has 22qDS, the risk of having a child in the family being affected is approximately 1 in 2000 to 4,000.   However, if one parent has 22qDS, they have a 50% chance of passing it on to each of their children.  In addition, even though 22qDS is passed down to about half the children of someone with 22qDS, it may cause different malformations and problems in each person in the family.  So if a parent with 22qDS has heart problems, half of their children are likely to have 22qDS, but none of them may have heart problems. 

4. What are some common features of 22qDS?

Despite the involvement of a very specific portion of chromosome 22, there is great variation in the features of this syndrome.  22qDS has had over 180 clinical features described.  Some of the more common features include: cleft palate, usually of the soft palate (the roof of the mouth nearest the throat which is behind the bony palate); velopharyngeal insufficiency; hypernasal speech; heart problems including, but not limited to, interrupted or right-sided aortic arch, tetralogy of Fallot, truncus arteriosus, and ventricular and/or atrial septal defects; similar faces (elongated face, almond-shaped eyes, wide nose, small ears); learning and behavioral difficulties; psychiatric disorders; eye problems; feeding problems that include food coming through the nose (nasal regurgitation) due to the cleft palate; recurrent middle-ear infections (otitis media); hypoparathyroidism (low levels of the parathyroid hormone that can cause low calcium and result in seizures); immune system problems which make it difficult for the body to fight infections; weak muscles (hypotonia); short height; curvature of the spine (scoliosis); and tapered fingers. 

5. How many of the manifestations of 22qDS are usually present?

Probably no individual with 22qDS has all the known clinical findings.  Many of the anomalies associated with the syndrome are not apparent at birth, or even in early childhood, primarily because they are behavioral, or in some cases because they are “silent” anomalies, meaning that they don’t cause problems. 

6. What kind of learning issues are involved in 22qDS?

For the large majority of children with 22qDS, specific learning disabilities become obvious by 7 or 8 years of age. Although mental retardation can occur in 22qDS, it is not common.  However, IQ scores have been noted to drop in children with 22qDS, often between 7 and 10 years of age, although this is highly variable.  The range of IQ scores associated with 22qDS is also very broad. Usually more language problems are seen in preschool and early grades and more nonverbal problems (e.g., math, drawing, hand writing) are seen as children with 22qDS get older. 

7. Do all children with 22qDS develop mental health problems?

No.  As is true with all clinical manifestations of genetic syndromes, it is rare for any single abnormality to be present in every case.  It is also true that even when present, not all anomalies have the same degree of severity.  In 22qDS, it appears that severe psychiatric problems like psychosis or schizophrenia occur in less than half of the people with 22qDS.  The current estimates are approximately 25-40% of people with 22qDS having a significant mental health problem, with schizophrenia accounting for about half of those problems (i.e., occurring in about 13-25% of individuals with 22qDS). 

8. What types of developmental issues are associated with 22qDS?

Developmental delay is a common manifestation in children with 22qDS, but it is variable with some children showing almost no early problems and others being quite delayed. The majority of children, however, tend to fall towards the outer limits of normal for most motor milestones. This delay may have multiple contributors commonly seen in people with 22qDS, including generalized hypotonia (low muscle tone), congenital heart disease, multiple hospitalizations and operations, chronic illness, and other factors that can restrict a child’s activity. Severe motor impairment is very uncommon among children with 22qDS. Speech and language milestones tend to be slightly more delayed, however, this is again very variable. The large majority of children with 22qDS do go through several "spurts" of motor development, especially between 3 and 4 years of age that tend to narrow the differences between themselves and other children quite a bit. By school age, the majority of children with VCFS tend to perform close to the normal range in terms of motors skills, although they may always be a little more hypotonic or "clutzier" than other kids. A similar spurt also occurs with speech and language. It would seem that children with VCFS have their own developmental profile that differs from that of other children. In general, most show significant "catch-up" before their fourth birthday.