22q Deletion Syndrome: Symptoms, Treatment + Podcast

Everything to know about 22q Deletion Syndrome, from the experts.

Podcast

Author and Contributing Experts to this Guide include:

Brenna Bentley Director, Patient Education at YourDNA.com LinkedIn

What is 22q Deletion Syndrome?

22q Deletion Syndrome is the most common chromosome deletion syndrome, and is roughly as common as Down Syndrome 1 . It’s estimated that between 1 in 3,000 to 6,000 children are born each year with 22q, but that number is probably a gross underestimation 2.

Individuals with 22q deletion syndrome, have a section of the q arm on the 22nd chromosome missing. Most of the time, this deletion occurred spontaneously, meaning that it occurred randomly and is not seen in the patient’s parents.

Conditions are termed as syndromes when they present with a number of identifying features. 22q deletion syndrome is no different.

There are many potential presenting issues such as: congenital heart diseases, palate abnormalities, immune deficiency, characteristic facial features, and learning disabilities 3. Because there are so many presenting features, and each patient may have only a few or several of the symptoms, diagnosis can be challenging in some cases.

In fact, researchers have identified more than 180 possible symptoms of 22q deletion syndrome. Due to the wide range of symptoms, this condition has historically gone by several different names:

  • 22q11 deletion syndrome
  • 22q11.2DS
  • DiGeorge syndrome
  • Velocardiofacial syndrome (VCFS)
  • Conotruncal Anomaly Face syndrome
  • Opitz G/BBB syndrome
  • Cayler Cardiofacial syndrome.
  • Sedlackova syndrome
  • Shprintzen syndrome

Part of the reason there are so many different names is that sub-specialists created names for various findings before anyone was able to link all of them together. For instance, Angelo DiGeorge, MD, an endocrinologist, focused on problems with calcium 4, while Robert Shprintzen, PhD, a speech pathologist, concentrated on palatal differences.

Many specialists were accurate in their own areas but none were able to see the bigger picture until a lab test was developed to detect the chromosomal deletion.

“It is a highly variable phenotype. No individual with 22q is going to be the same as another,” said Emily Palen, a licensed genetic counselor who coordinates the 22q developmental specialty clinic at Geisinger's Autism & Developmental Medicine Institute in Lewisburg, Pennsylvania.

What Causes 22q Deletion Syndrome?

In clinical terms, “22q deletion is caused by about a three megabase deletion on chromosome 22 on the long arm of that chromosome,” said Palen.

Most chromosomes have two arms, a short arm called “p,” and a long arm called “q.” Under special staining, chromosomes will appear “banded”. In order for researchers to clearly communicate about findings, the chromosome bands are numbered.

The name, 22q11.2 deletion syndrome, specifies the specific region on chromosome 22 that is missing.

“A three megabase deletion, is about three million based pairs, or the genetic letters that make up our genetic code. Those three million base pairs are missing from that section of the chromosome. The loss of several genes in that region cause some of the hallmark features of the 22q condition.” – Palen

About 15% of people have a smaller than standard size deletion, which is often referred to as “nested” or “distal” deletions 5.

Most children with 22q deletion syndrome, are missing 30 to 40 genes 6. Researchers don’t know the exact function of many of these genes. However, the missing the gene TBX1 on chromosome 22 likely causes the syndrome's most common physical symptoms like heart issues or cleft palate 7.

The loss of another gene (COMT) may also explain the higher risk for behavior problems and mental illness 8.

It can be inherited, but most times 22q arises de novo, meaning it is a new change that is occurring for the first time in the family. About 90-95% of the 22q deletions are new and unique in an individual and they have not been inherited from either parent 9. In other words, it can be inherited, but most of the time, it is not.

Signs and Symptoms of 22q Deletion Syndrome

“Every person will be different from each other that has this deletion. If we pull back and try to find physical commonalities, some of the facial features or physical features that you might notice are ears tend to be smaller and maybe a little bit squared off at the top. Eyelids tend to be hooded, so the skin between the brown bone and the lash line is a little bit droopier. The bridge of the nose is more prominent, and the chin tends to be rather small,” said Palen.

“Individuals might be a little bit smaller, shorter than other members of their family. Some of the other features of the condition are things that you can't see with the naked eye,” she added.

Depending on the patient’s age, there can be different presenting signs and symptoms. When a child is first born and as the age into infancy, some of the more common signs are congenital heart defects, frequent infections, a nasally speech, low calcium, feeding problems, and developmental delays 10.

“We tend to see cardiac defects or congenital heart defects, cardiac abnormalities that are present from birth. That may be a hole in the heart or something called Tetralogy of Fallot, which is a few different cardiac abnormalities all occurring at the same time, or maybe an interrupted aortic arch. These are typically cardiac abnormalities that affect the aorta of the heart,” said Palen.

According to Palen, “We may also see palatal abnormalities, so individuals with this condition may have a cleft pallet or a bifid uvula, which is that little dangly bit in the back of your neck at the back of your throat. That might be split in two.”

We may also see something called velopharyngeal insufficiency. What that means is the soft pallet at the back of your pallet doesn't close against the back of the neck.

What that can cause is air flow when speaking that makes the speech sound a little bit different.

“If you chat with a little kid who has this condition, their speech might sound a little bit different than other kids who don't have this deletion. That's typically caused by that VPI or that velopharyngeal insufficiency.”

As the child gets older and moves into adolescence and adulthood, new features might arise such as psychiatric illness.

“22q is also associated with some mental health differences. That's usually one of the things that people can cling onto. If you do any Googling, you may see that this condition is associated with a psychiatric condition called schizophrenia. That can be very overwhelming for newly diagnosed individuals and their families. We can also see things like increased anxiety, mood differences, things like that,” said Palen.

In fact, there are more than 180 identified signs and symptoms of 22q deletion syndrome. The most affected symptoms include:

  • Cardio-vascular
  • Cleft palate
  • Feeding difficulties
  • Immunization problems
  • Growth hormone deficiencies
  • Delayed neurological and psychological developments
  • Speech problems
  • Renal abnormalities

However, this is not an extensive list. The range of signs and symptoms can be quite broad including congenital birth defects, cardiac findings, craniofacial/oral findings, learning differences, ear/hearing findings, differences in the endocrine system, immune deficiency, skeletal findings, skin/hair differences, and vascular anomalies. You can find a full list of signs and symptoms at www.22qcentral.com

What does 22q11.2 Deletion Syndrome Look Like?

Individuals with 22q Deletion Syndrome might have some slight differences in their features that could help with diagnoses. Individuals might have a small mouth and jaw.

When you look at their eyes you might that the corners of their eyes are turned slightly upward, and that their eyelids might seem to be a bit droopy. They might also seem to have a broad tip of their nose.

The ears might a bit squared and rotated down. It is important to remember that these changes are often small and not everyone with 22q Deletion syndrome will have these features 11.

Prevalence and Risk Factors for 22q Deletion Syndrome

“Anyone can have 22q deletion syndrome. It doesn't discriminate in regards to a person’s sex, or race, or anything like that,” said Palen.

“We know that if someone carries the deletion, and has this condition, there's a 50-50 chance with each pregnancy that the deletion could be passed on to the child. If someone doesn't carry the deletion, we can't say there's a zero percent chance because it's possible the deletion could occur independent of being inherited. Instead, we say someone has a low risk if the parent isn't a carrier,” she added.

When thinking about prevalence, it can be difficult to come to an absolutely number. Due to the wide range of signs and symptoms, there is an accompanying range of prevalence estimates.

Doctor Scott Hickey is an assistant professor of clinical pediatrics through the Ohio State University College of Medicine and a board-certified clinical geneticist and co-director at the 22q Center Multidisciplinary Clinic at Nationwide Children's Hospital in Columbus, Ohio.

He estimates, “…the prevalence is somewhere between one in 2,000 and one in 3,000 people. There was a study in 2015 of pregnant women where they found evidence that it could be as high as one in 1,000. That was just one study, and I would tend toward it being closer to one in 2,000 to one in 3,000, which does make it the most common chromosomal microdeletion syndrome.”

“By comparison, down syndrome is probably found in about one in 1,000 people. So, down syndrome might be about twice as common,” added Dr. Hickey.

There does not appear to be a higher prevalence among certain populations regarding 22q deletion syndrome 12.

“In terms of the question of certain populations, 22q is a condition that seems to occur due to some specific predisposition that all humans have to possibly have a child with this condition. That's a predisposition I think we would expect would cut across all races and ethnicities. Although I don't have exact data across all different types of indigenous people and everything, we would expect it would be about the same in most populations,” added Dr. Hickey.

Diagnosis of 22q Deletion Syndrome

If an individual is exhibiting some of the signs and symptoms mentioned above, then 22q Deletion Syndrome might be suspected. In order to confirm the diagnosis, a DNA sample, typically either blood or saliva, will need to be sent to a laboratory for analysis.

There are a number of different tests that could be used, but most commonly the condition is identified through microarray analysis. You might also hear about Fluorescence in situ hybridization (FISH).

“Sometimes if a patient is seen by a geneticist or another provider who really thinks that it's 22q, they may do very targeted testing to look for just that deletion and nothing else,” says Palen.

“Other times, a provider says, ‘I think it might be 22q, but I might be wrong.’ They'll maybe order a test called a chromosomal microarray to look any deletion or duplication on any of the chromosomes.

“Other providers might offer up broader testing, something called whole exome sequencing, which some of the time we can detect these types of deletions as well.”

How we have diagnosed 22q Deletion Syndrome has changed over time.

“In the late 90s and the early 2000s, to make the diagnosis, you had to use fluorescence in SITU hybridization or FISH testing,” noted Dr. Hickey.

Academic institutions led the way with chromosomal microarray testing, but by 2010, there were multiple different genetic societies recommending genetic testing as the frontline diagnosis for intellectual disability, autism, and multiple congenital anomalies types of presentation.

“This required the provider to say, ‘I think this might be 22q deletion syndrome. Let's check.’ Now the way that chromosomal testing has developed over time, we as geneticists don't have to be quite as smart anymore. We can just employ a test called a microarray that looks at copy number changes across all the chromosomes,” said Dr. Hickey.

We don't have to think of 22q deletion syndrome. We can just say, "Is it any chromosome condition?", and it will come back and let us know if it's 22q deletion syndrome,” he added.

This can be especially helpful when someone other than a genetics provider is on the frontlines of a diagnosis. A primary care physician or neonatologist only needs to take into account that symptoms may indicate that a chromosome difference is present.

When geneticists are involved, they use two different skillsets to make a diagnosis. They use genetic testing and interpretation of the genetic testing, but also use dysmorphology. This means physically looking at patents for specific patterns as part of the overall context of what’s going on.

According to Dr. Hickey, “if there’s a medical concern, we look at the baby’s facial features. Children with 22q deletion syndrome often have a sort of bulbous or rounded nasal tip. Their ears are often formed a little bit differently. They're a little overfolded and in low set in some cases. Then their mouth is often small with the corners of their mouth are downturned. Then their chin is often small. Some of these features are reflective of what's called low muscle tone.”

“It's important to point out that children with lots and lots of different genetic conditions have low muscle tone. So, just because a child has low muscle tone, I wouldn't necessarily say that they have 22q deletion syndrome.

“If a baby is born with a certain type of heart defect, if they have a calcium problem, immune problems, a cleft pallet or other things that might make us think of 22q deletion syndrome, then that would be a first line test we would want to do.”

A diagnosis can take place at almost any age. Some people aren’t diagnosed until they’re in their 30s or 40s according to Palen. This could be because their symptoms or features are subtle and mild, or they simply weren’t diagnosed as someone with 22q when they were younger.

Others go undiagnosed because they never met with the right provider or a genetic test was never ordered for them.

Treatment and Care Options for 22q Deletion Syndrome

When someone is first diagnosed with 22q deletion syndrome, inevitably the first question asked is, “Is there a cure?”

Unfortunately, at this time, the answer is no.

“We don't have the ability to replace that missing section of 22q. A lot of families say, ‘Well, if it's missing, can't we just put it back?’ We don't have that technology or that ability right now,” explained Palen.

“Your genetic information is present and found in all of the trillions of cells of your body. So, anything that would be considered ‘cure’ would have to reach and have its effect and change the genetics in every one of those trillions of building blocks of your body, which is just a real challenge,” added Dr. Hickey.

However, the upside is that in many instances, providers are effective in treating and managing many of the symptoms and features of 22q deletion syndrome. Thanks to management guidelines, patients with 22q receive coordinated and individualized care from multidisciplinary teams of clinicians that can be drawn from more than 20 specialties 13.

After an 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

After the initial evaluation, a care team will work with you to identify a plan that is specific to the individual. Since everyone with 22q deletion syndrome is different, the care and management will be different too. Some examples of care can be found below, with percentages pulled from Dr. McDonald-McGinn’s research 14.

Cardiology – About 75 percent of children have some type of heart defect, many require surgery to correct the problem, often as newborns.

Child Development – The majority have motor milestone delays, such as walking, and delays in emergence of language and specific learning differences. This requires special help in school, including those with autistic features or behavioral differences like ADHD, OCD, perseverations, anxiety, and psychosis.

However, all children with 22q benefit from strategies for early intervention, including such things as occupational therapy, physical therapy, and speech therapy/sign language in young childhood followed by specific learning style interventions

Cleft Palate – 75 percent of children have differences in their palate allowing fluids to come through their nose in infancy (nasal regurgitation) and later leading to hypernasal speech. Surgery is often performed to alleviate this problem.

Endocrinology – About 50 percent of children have low calcium levels and some children will need calcium supplements during times of illness or stress such as at puberty or post operatively. Some children will have trouble with an under- or over-active thyroid and some have growth hormone deficiency, both of which respond well to treatment.

ENT and Audiology – Ear infections and hearing loss are common caused by structural differences, like a vascular ring or laryngeal web or associated with reflux. Many children benefit from ear tube placement or hearing aids. In some cases, more complex care is required from an Otolaryngologist.

Gastroenterology/Feeding Team – 33 percent of children have significant problems with feeding and swallowing, including gastroesophageal reflux (GERD) and dysmotility leading to reflux and constipation. Other less common issues include umbilical hernia, intestinal malrotation, an absent anal opening, Hirshsprung’s disease, or a diaphragmatic hernia where loops of bowel can be in the chest. Most common feeding issues are resolved with medical assistance by school age.

Immunology/Rheumatology – 75 percent of children have immunodeficiency and must deal with recurrent infections, failure to respond normally to vaccines, and are not able to receive live viral vaccines. Most issues resolve in infancy. Patients are also more likely to get autoimmune diseases, for example, Juvenile Rheumatoid arthritis, Idiopathic Thrombocytopenia, Autoimmune Neutropenia, Grave’s disease, and Vitiligo.

Neurology – where, rarely, children suffer seizures that are not related to their low calcium levels and/or structural brain differences/a small head. Occasionally, children will have spina bifida.

Ophthalmology – Some children will also have eye problems such as droopy eyelids, differences in the whites of their eyes, in the colored parts of their eyes, and differences with their eye muscles. Some of these problems require surgical treatment eye patching.

Orthopedics – Some children have variations in the way the vertebrae of the spine are formed at the neck, resulting in reduced room surrounding the spinal cord at the neck. Surgery often corrects this.

Other suffer from bone differences in the chest, a curvature of the spine, extra ribs, extra fingers and toes, or in a few cases, premature fusion of the bones of the skull. All of these can be helped through surgery.

Urology – One-third of children have variations in the way their kidneys are formed or how they function, including malformed kidneys, kidney reflux, problems with infections, differences in the way the genito-urinary system may be formed, and potty training. Depending on the problem, corrective surgery may help 15.

Potential Complications from 22q Deletion Syndrome

A small number of children with severe heart defects and immune system problems caused by 22q deletion syndrome will not survive the first year of life 16. But most children who are treated early in life will survive and grow into adulthood.

Because there are so many symptoms, the possibility of potential complications is wide and will vary from patient to patient.

Can 22q Deletion Syndrome be Prevented?

About 90-95% of all cases of 22q deletion syndrome happen by chance. Therefore, only 5-10% of cases are inherited from a parent 17. As such, there isn’t really any way to prevent this condition.

If an individual with 22q deletion syndrome is considering starting and family and is curious if the child will also have the condition, there are preconception and prenatal options.

If a couple with a known 22q deletion, has yet to conceive, they have the option of pre-implantation genetic diagnosis. The couple would first undergo in vitro fertilization, and then the embryos would be screened for 22q deletion syndrome.

Only embryos without the deletion would be implanted into the mother’s uterus.

After a couple conceives, they can choose to undergo non-invasive prenatal testing (NIPT). If the test results come back indicating that 22q might be present, then, individuals may choose to pursue diagnostic testing, such as an amniocentesis.

This test looks at fetal cells to see if there are any deletions or duplications that might indicate developmental concerns or medical concerns, such a 22q.

“It's every family's choice what information they want to know about their child or their pregnancy,” noted Palen.

“Sometimes if 22q isn't on our radar, the parent isn't a carrier, and there's no family history. Instead, maybe ultrasound findings come back that are indicative of this condition. We may see some cardiac abnormalities that we know are more common in 22q. A provider would likely discuss that with the family and see if they'd like to pursue any testing.”

You may also want to consult with a genetic counselor if you have questions or you want help planning future pregnancies.

Prognosis of 22q Deletion Syndrome

The prognosis of someone with 22q deletion syndrome has changed in recent years. Many children who died in infancy before sophisticated cardiac surgeries and advanced antibiotics are now winning the battle against this condition.

The mortality rate in children is about 4% and those who pass away usually do so at a very early age, on average at 4 months 18.

“The question of a shortened lifespan is one that I get asked a lot by parents, and it's a very emotionally charged question. In response, I think it's important to be kind of specific about it. For example, if a child has a really significant structural difference in the anatomy of their heart, that is always going to affect life expectancy,” said Dr. Hickey.

“There are other things that are known to affect life expectancy by themselves, including intellectual disability and then schizophrenia. There is a substantial risk for neuropsychiatric conditions such as schizophrenia and 22q deletion syndrome. Although, the majority won't have that issue. But, those things effect mortality too,” added Dr. Hickey.

This is not to say that those who survive don’t experience medical problems throughout their lives, because they do.

And the news on prognosis is improving.

“Each subsequent study that I see on this, the median age of survival gets longer. So, I think that's encouraging,” said Dr. Hickey.

“The last report that came out of Canada of an adult clinic, a prominent adult clinic in Toronto was that the median age of death was in the mid to late 40s, which I know is not what people want to hear. That also includes people with significant congenital heart disease.

If a child doesn't have significant congenital heart disease, I think we would expect more than that. I think with guidelines and modern medical care, I think we expect to continue to improve over time.”

What to do Next: Living with 22q Deletion Syndrome

A diagnosis of 22q deletion syndrome can be a shock and overwhelming. Fortunately, there are several resources you can tap for more information and support. Some of those include:

The International 22q Foundation provides several resources to help those afflicted by 22q, seeking to improve the quality of life through family and professional partnerships.

The 22q Family Foundation has several links on their website to help you connect with resources near you. This includes several online support groups listed by state.

“22q and You” Center The Children's Hospital of Philadelphia 3401 Civic Center Blvd Philadelphia, PA 19104 USA Phone: (215) 590-2920 Toll-free: (800) 879-2467

Genetic and Rare Diseases (GARD) Information Center PO Box 8126 Gaithersburg, MD 20898-8126 Phone: (301) 251-4925 Toll-free: (888) 205-2311 Website: http://rarediseases.info.nih.gov/GARD/

Chromosome 22 Central – dedicated to support for the disorders of Chromosome 22.

Chromosome Disorder Outreach

National Organization for Rare Disorders/Chromosome 22q11.2 Deletion Syndrome

Referenced Sources

  1. McDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A., . . . Bassett, A. S. (2015). 22q11.2 deletion syndrome. Nat Rev Dis Primers, 1, 15071. doi:10.1038/nrdp.2015.71
  2. Botto, L. D., May, K., Fernhoff, P. M., Correa, A., Coleman, K., Rasmussen, S. A., . . . Campbell, R. M. (2003). A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics, 112(1 Pt 1), 101-107. doi:10.1542/peds.112.1.101
  3. McDonald-McGinn DM, H. H., Emanuel BS, et al. (2020). 22q11.2 Deletion Syndrome.
  4. DiGeorge A. (1965). Discussion on a new concept of the cellular immunology. Journal of Pediatrics, 67, 907-908.
  5. McDonald-McGinn, D. M., & Zackai, E. H. (2008). Genetic counseling for the 22q11.2 deletion. Dev Disabil Res Rev, 14(1), 69-74. doi:10.1002/ddrr.10
  6. McDonald-McGinn, D. M., & Zackai, E. H. (2008). Genetic counseling for the 22q11.2 deletion. Dev Disabil Res Rev, 14(1), 69-74. doi:10.1002/ddrr.10
  7. Jerome, L. A., & Papaioannou, V. E. (2001). DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1. Nat Genet, 27(3), 286-291. doi:10.1038/85845
  8. Vorstman, J. A., Turetsky, B. I., Sijmens-Morcus, M. E., de Sain, M. G., Dorland, B., Sprong, M., . . . Kemner, C. (2009). Proline affects brain function in 22q11DS children with the low activity COMT 158 allele. Neuropsychopharmacology, 34(3), 739-746. doi:10.1038/npp.2008.132
  9. McDonald-McGinn, D. M., Tonnesen, M. K., Laufer-Cahana, A., Finucane, B., Driscoll, D. A., Emanuel, B. S., & Zackai, E. H. (2001). Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net! Genet Med, 3(1), 23-29. doi:10.1097/00125817-200101000-00006
  10. McDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A., . . . Bassett, A. S. (2015). 22q11.2 deletion syndrome. Nat Rev Dis Primers, 1, 15071. doi:10.1038/nrdp.2015.71
  11. McDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A., . . . Bassett, A. S. (2015). 22q11.2 deletion syndrome. Nat Rev Dis Primers, 1, 15071. doi:10.1038/nrdp.2015.71
  12. McDonald-McGinn, D. M., Kirschner, R., Goldmuntz, E., Sullivan, K., Eicher, P., Gerdes, M., . . . Zackai, E. H. (1999). The Philadelphia story: the 22q11.2 deletion: report on 250 patients. Genet Couns, 10(1), 11-24.
  13. Bassett, A. S., McDonald-McGinn, D. M., Devriendt, K., Digilio, M. C., Goldenberg, P., Habel, A., . . . Vorstman, J. (2011). Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr, 159(2), 332-339.e331. doi:10.1016/j.jpeds.2011.02.039
  14. McDonald-McGinn, D. M., & Sullivan, K. E. (2011). Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore), 90(1), 1-18. doi:10.1097/MD.0b013e3182060469
  15. Healthcare Guidelines. The International 22q11.2 Foundation. Retrieved online, 2020.
  16. Repetto, G. M., Guzmán, M. L., Delgado, I., Loyola, H., Palomares, M., Lay-Son, G., . . . Alvarez, P. (2014). Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study. BMJ Open, 4(11), e005041. doi:10.1136/bmjopen-2014-005041
  17. McDonald-McGinn, D. M., Tonnesen, M. K., Laufer-Cahana, A., Finucane, B., Driscoll, D. A., Emanuel, B. S., & Zackai, E. H. (2001). Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net! Genet Med, 3(1), 23-29. doi:10.1097/00125817-200101000-00006
  18. Repetto, G. M., Guzmán, M. L., Delgado, I., Loyola, H., Palomares, M., Lay-Son, G., . . . Alvarez, P. (2014). Case fatality rate and associated factors in patients with 22q11 microdeletion syndrome: a retrospective cohort study. BMJ Open, 4(11), e005041. doi:10.1136/bmjopen-2014-005041

Transcript

Brenna: You are listening to the Rare Disease Connection, a production of Aspect Health and RareDisease.com. Sometimes I find myself thinking about the intricacies of genetics. From just 46 chromosomes comes an entire person. There is so much information packed into each of ourselves, and scientists are just beginning to understand the nuances of us. On this podcast, we've talked about conditions caused by changes in a single gene or conditions involving an entire extra chromosome. Brenna: Today, we're going to talk about what happens when you're missing a region on chromosome 22. Rare Disease Connection and our additional resources on RareDisease.com and YourDNA.com brings together the people whose expertise can explain what you're facing from diagnosis to prognosis to treatment options all the way to questions like, "Who do I talk to? Where are the people who have been through this before?" You'll find those answers here from doctors, geneticists, academics, genetic counselors, patient organizations, other patients and their families, they're all within your reach. We're here to connect you. This is Rare Disease Connection. Brenna: Hey everyone. This is Brenna, Co-Host of Rare Disease Connection and Director of Patient Education at YourDNA.com. Today, I'm going to bring you conversations with three experts on 22q Deletion Syndrome. Before we get started, you should know that this podcast is just the beginning. We have taken the information from this podcast and added additional resources, explanations, links and references for you in a downloadable guide. You can get your free copy by going to RareDisease.com/22q. That's RareDisease.com/22q. So, let's get started. Brenna: Our first guest today is Emily Palen, a licensed genetic counselor currently working at Geisinger's Autism & Developmental Medicine Institute in Lewisburg, Pennsylvania. She has been there since 2016 and coordinates their 22q developmental specialty clinic. Welcome Emily. Brenna: Why don't you start out just telling us a little bit about yourself? Emily Palen: Sure. My name is Emily Palen. I'm a licensed certified genetic counselor and research coordinator at Geisinger's Autism & Developmental Medicine Institute here in Lewisburg, Pennsylvania. I graduated from Boston University's Genetic Counseling Training program in 2016, and I've been here at Geisinger ever since. Part of my work at Geisinger includes coordinating our 22q Specialty Clinic here at the institute. Brenna: That sounds wonderful. Speaking from your experience as a genetic counselor, what immediately comes to mind when you hear 22q deletion? Emily Palen: Yeah. A few different things come to mind. First, is a highly variable phenotype. No individual with 22q is going to be the same as another. I also think about a fierce and loving network of families. They're some of the most incredible families that I've had the privilege of working with. Then something very special to 22q is I feel that the community of researchers and medical providers is highly engaged, supportive and forward thinking. So, those are the main things that come to mind when I think about this particular condition. Brenna: Yeah, all really good things, positive things. Emily Palen: Yeah, definitely. Brenna: Using your experience as a genetic counselor and trying to understand what's actually occurring, what's going on genetically that causes 22q deletion? Emily Palen: Yeah, great question. 22q deletion is caused by about a three megabase deletion on chromosome 22 on the long arm of that chromosome. So, that's about three million based pairs, or the genetic letters that make up our genetic code. So, those three million base pairs are missing from that section of the chromosome. The loss of several genes in that region cause some of the hallmark features of the condition. Brenna: Is this inherited? Is this something that someone has gotten from one of their parents, or were they just born with it? Emily Palen: Yeah, so it can be inherited. As far as we understand it right now, most of the time these deletions, about 90% of the time, arise de novo, meaning that they're new and unique in the individual and weren't inherited from either parent. It's certainly possible that it could have been inherited from a parent in some of the cases. Brenna: Okay, so we know that maybe sometimes it's inherited, but most of the time it's not. Thinking about it as a whole, are there certain people who are more likely to have 22q Deletion Syndrome? What kind of chances to have a child with this condition? Emily Palen: Yeah, great question. Anyone can have 22q Deletion Syndrome. It doesn't discriminate against sex or race or anything like that. Anyone could have this condition. We know that if someone carries the deletion, so if someone has this condition, there's a 50/50 chance with each pregnancy that the deletion could have been passed on to the child. If someone doesn't carry the deletion, we can't say there's a zero percent chance because it's possible the deletion could occur out of the blue. We would say have a low risk if the parent isn't a carrier of that condition. Brenna: Thinking about how we actually make this diagnosis, I guess first time you see a patient, you might walk in. If you were to see pictures of someone with this condition, what would we see? What would someone look like? Emily Palen: Yeah. I'll sound like a broken record throughout this entire recording, but every person will be different from each other that has this deletion. If we pull back and try to find physical commonalities, some of the facial features or physical features that you might notice are ears tend to be smaller and maybe a little bit squared off at the top. Eyelids tend to be hooded, so the skin between the brown bone and the lash line is a little bit droopier. Bridge of the nose is more prominent, and the chin tends to be rather small. Those are some of the facial features that you would see. Individuals might be a little bit smaller, shorter than other members of their family. Some of the other features of the condition are things that you can't see with the naked eye. Brenna: Thinking about those things that we can't see with the naked eye, what are those? What are things that some people should be watching for? Emily Palen: 22q Deletion Syndrome, there are a few things that tend to go along with it. Again, everyone will be different who carries a deletion. We tend to see cardiac defects or congenital heart defects, so cardiac abnormalities that are present from birth. Maybe a hole in the heart or something called Tetralogy of Fallot, which is a few different cardiac abnormalities all occurring at the same time or maybe an interrupted aortic arch. These are typically cardiac abnormalities that affect the aorta of the heart typically. Emily Palen: We may also see palatal abnormalities, so individuals with this condition may have a cleft pallet or a bifid uvula, which is that little dangly bit in the back of your neck at the back of your throat. That might be split in two. We may also see something called velopharyngeal insufficiency . What that means is the soft pallet at the back of your pallet doesn't close against the back of the neck. What that can cause is air flow when speaking that makes the speech sound a little bit different. If you chat with a little kid who has this condition, their speech might sound a little bit different than other kids who don't have this deletion. That's typically caused by that VPI or that velopharyngeal insufficiency. Emily Palen: Individuals with this condition might also have immune deficiencies, so ear infections a lot or getting colds all the time. So, their immune system isn't quite as strong as other people. We usually also see some sort of developmental delay. Maybe that's across the board in all of the developmental domains or maybe in just a couple. We tend to see developmental milestones lagging behind their typical peers. Emily Palen: 22q is also associated with some mental health differences. That's usually one of the things that people can cling onto. If you do any Googling, you may see that this condition is associated with a psychiatric condition called schizophrenia. That can be very overwhelming for newly diagnosed individuals and their families. We can also see things like increased anxiety, mood differences, things like that. Brenna: Thinking about all of those things, and I know how they might not be present in every single person and everyone's going to be different. When does someone receive a diagnosis typically? Is there a typical age? Is there a certain test that they have to undergo? Emily Palen: It totally depends. I know individuals who weren't diagnosed until they were in their 30s or 40s. That might be because maybe their symptoms or their features were more subtle or more mild and they just weren't identified as someone who might have this condition when they were younger. Maybe they just slipped through the cracks in terms of genetic testing. They never met with a provider who had offered that up to them or their families. Emily Palen: In my pediatric practice, our clients with 22q tend to be picked up in the NICU. Usually babies who have 22q may have those cardiac abnormalities that I was talking about or low calcium levels, which can cause seizures and other medical concerns. Maybe a doctor notices that have some other characteristic facial features or physical features consistent with the syndrome. A lot of the little friends that I have who are diagnosed with 22q was because they exhibited those signs or symptoms early on. Emily Palen: The types of tests vary as well. There are many different ways to detect this deletion. Sometimes if a patient is seen by a geneticist or another provider who really thinks that it's 22q, they may do very targeted testing to look for just that deletion and nothing else. Maybe a provider says, "I think it might be 22q, but I might be wrong." They'll maybe order a test called a chromosomal microarray, which will look for any deletion or duplication on any of the chromosomes. 22q would be detected by that technology. Then other providers might offer up broader testing, something called whole exome sequencing, which some of the time we can detect these types of deletions as well. It really all depends. The kind of clinical management or care isn't dictated by which test is ordered. It just kind of clarifies the diagnosis. Brenna: I know you mentioned that you see several individuals who are picked up in the NICU, but I guess going before that, is there any prenatal testing that's available for this condition? Emily Palen: Yes, absolutely. There are many different ways that this might be detected in the prenatal period. Some individuals may choose to pursue non-invasive prenatal screening. Sometimes that screening test might come back indicative of possibilities that this deletion is present. Those individuals may choose to pursue diagnostic testings, such as an amniocentesis, which would be looking at the fetal cells to see if there are any deletions or duplications that might be causative of other developmental concerns or medical concerns such a 22q. Emily Palen: If a parent is a known carrier, so if you have an individual who's known to carry 22q, and their pregnant or family planning, they might choose to pursue that diagnostic testing that I mentioned and amniocentesis or not. It's every family's choice what information they want to know about their child or their pregnancy. Sometimes if 22q isn't on our radar, the parent isn't a carrier, there's no family history, nothing like that, maybe ultrasound findings come back that are indicative of this condition. Maybe they notice some cardiac abnormalities that we know are more common in 22q. So, the provider would likely discuss that with the family and see if they'd like to pursue any testing. Brenna: Is there a cure? Emily Palen: Yeah. That's a question I get from a lot of our families who are newly diagnosed. At this time, we don't have the ability to replace that missing section of 22q. A lot of families say, "Well, if it's missing, can't we just put it back?" We don't have that technology or that ability right now. The bright side of 22q is we're really good at treating and managing all of the symptoms and features. If someone has immune deficiency, we'll get them set up with immunology. If they have cardiac defects, we'll get them set up with cardiology. Emily Palen: So, there's very clear protocols and guidelines that we can follow to take the best care of these individuals that we can. But, no, at this time we don't have a cure or a way to correct that genetic deletion. Brenna: In closing, you've seen a lot of individuals and families who have this condition. What's your best advice for someone who's just been diagnosed or who has a loved one who was just diagnosed? Emily Palen: I think the first thing that comes to mind is to tell that individual or their family that they're not alone. 22q is one of the most common microdeletion syndromes. There are many medical providers and researchers who are dedicated to taking the best possible care of these individuals. So, if and when you or your loved one or family members are ready, the 22q community is going to be here with open arms. They're some of the most engaged and supportive individuals I've ever met. So, the community is really strong. I think that can be very, very helpful for some individuals facing a new diagnosis for themselves or their family member. Brenna: Thank you, Emily, for joining us today. Brenna: Whether you've interacted with a genetic counselor yet or not, they play an invaluable role in the journey of anyone diagnoses with a rare genetic disease. If you have questions about 22q Deletion Syndrome, I would recommend looking at NSGC.com to find a genetic counselor near you. Brenna: Our next guest is Doctor Scott Hickey. He's a clinical geneticist at Nationwide Children's Hospital in Columbus, Ohio. Doctor Hickey works on a number of different specialty clinics, one of which being the 22q Center Multidisciplinary Clinic. Brenna: Thank you for taking the time to speak with us today. Why don't you start out by just telling us a little bit about yourself? Doctor Hickey: Yeah, my name is Scott Hickey. I'm an assistant professor of clinical pediatrics through the Ohio State University College of Medicine in affiliation with Nationwide Children's Hospital in Columbus, Ohio. I'm a board certified general pediatrician and board certified clinical geneticist. I'm the staff geneticist and one of the co-directors of our 22q Center through our hospital, which is a multidisciplinary clinic for patients with 22q11 Deletion Syndrome. Brenna: Thinking about your experience as a pediatrician and as a clinical geneticist, what immediately comes to mind when you hear 22q Deletion Syndrome? Doctor Hickey: Well, it's one of those conditions that's quite variable in terms of the extent to which it effects the quality of patients. So, everybody can be quite different, and everybody has their own unique set of challenges. I think that's one of the reasons that it's important for a medical system and hospital to have resources across a wide range of disciplines to help provide for these patients. Brenna: Thinking about 22q Deletion Syndrome as a whole, how common is this condition? Is it more prevalent in certain populations or areas of the world? Doctor Hickey: Well, I think the vast estimates are that the prevalence is somewhere between one in 2,000 and one in 3,000 people. There was a study in 2015 of pregnant women where they suggested that ... they found evidence that it could be as high as one in 1,000. That was just one study, and I would tend toward it being closer to one in 2,000 to one in 3,000, which does make it the most common chromosomal microdeletion syndrome. By comparison, down syndrome is probably found in about one in 1,000 people. So, down syndrome might be about twice as common. Doctor Hickey: It is interesting because most people in the general public when you talk to them, I often use down syndrome as a point of reference, because most people are familiar with that. Whereas for whatever reason with 22q Deletion Syndrome, most people have not. In terms of the question of certain populations, I doubt it. It's a condition that really it's a recurrent condition due to some specific predisposition that all humans have to possibly have a child with this condition. That's really a predisposition that I think we would expect would cut across all races and ethnicities. Although I don't have exact data across all different types of indigenous people and everything, we would expect it would be about the same in most populations. Brenna: Sure. Absolutely. Throughout your career in working with this condition, what has surprised you the most? Doctor Hickey: Well, I think it's the variability of the condition, because a lot of things have changed in terms of genetic testing technology. In the late 90s and the early 2000s, in order to make the diagnosis, you had to use fluorescence in situ hybridization or FISH testing, which was, without getting into the technical parts of it, required the provider to say, "I think this might be 22q Deletion Syndrome. Let's check." Now the way that chromosomal testing has developed over time, we as geneticists don't have to be quite as smart anymore. We can just employ a test called a microarray that looks at copy number changes across all the chromosomes. Doctor Hickey: So, we don't really have to ask questions. We don't have to think of 22q Deletion Syndrome. We can just say, "Is it any chromosome condition?", and it will come back and let us know if it's 22q Deletion Syndrome. What we learned from that is that in many cases, even though we weren't thinking of that condition specifically, that's what turned out to be the cause. So, it always looked like what we thought it would look like because that's what we were looking for. Now we've seen all the many other different ways that this condition can present to doctors. Brenna: Right. As you casted a larger net, you were able to identify patients who might have had symptoms or signs that might not have been the traditional symptoms or signs initially looked for. Doctor Hickey: Right. That's correct. That's also helpful, because it's not always a genetics provider. In fact, it's often not a genetics provider who's evaluating these patients on the frontline. It might be a primary care physician. It might be a neonatologist. It might be in another specialty because of some other health condition that is kind of the first thing that gets pediatrician's concerned. So, it's helpful to have a test now that allows them to just sort of ask a general question, "Could it be any chromosome difference?" Then it comes back that it's a 22q deletion without requiring the expertise of a geneticist looking at the patient with a little more detail or eye toward that question. Brenna: Sure. That's the first line test for intellectual disability, development delays. It's typically a go-to for that microarray, right? Doctor Hickey: Right. Chromosomal microarray really became quite popular clinically in around 2006 to 2008 range, depending what institution you're at. The academic institutions, I think, tended to be a little bit more on the cutting edge, so to speak, side of that. Then by 2010, there were multiple different genetic societies recommending that as the frontline test for intellectual disability, autism, multiple congenital anomalies type of presentation. Brenna: Keeping in this [inaudible 00:21:11] with diagnosis, if you were able to see these patients, I know often you're stating geneticists aren't always the frontline, but when you are completing a physical exam, are there certain features that might make you suspicious of this condition? Doctor Hickey: As geneticists, I guess we have two different skillsets that are sort of our area of expertise. One of them is genetic testing and the interpretation of genetic testing. The other one is what's called dysmorphology, which refers to looking at babies, children, patients and looking for specific patterns in the way that they look in the context of whatever's going on. So, I think it's important to sort of preface it by we look for these things in babies who are having some sort of problem. It's a different situation if you see features in a baby who's otherwise healthy and growing and developing normal. Doctor Hickey: So, in the context of some sort of medical concern, a lot of it is looking at the baby's facial features. So, children with 22q Deletion Syndrome are often described as having a sort of bulbous or rounded nasal tip. Their ears are often formed a little bit differently. They're a little overfolded and in low set in some cases. Then their mouth is often small with the corners of their mouth are downturned. Then their chin is often small. Some of these features are reflective of what's called low muscle tone. Doctor Hickey: Children with 22q Deletion Syndrome often have low muscle tone. It's important to point out that children with lots and lots of different genetic conditions have low muscle tone. So, just because a child has low muscle tone, I wouldn't necessarily say that they have 22q Deletion Syndrome. If a baby is born with a certain type of heart defect, if they have a calcium problem, immune problems, a cleft pallet or other things that might make us think of 22q Deletion Syndrome, then that would be a first line test that we'd want to do. Brenna: It sounds like you really have to take the whole picture into account. Doctor Hickey: Yes, that definitely correct. That's a really important point, because my experience in dealing with patient families is that there's always this question of sort of what does that little particular point mean like, "You see this on a baby. What does that mean?" It's a really important overarching point that we're not looking at one thing. We're looking at the whole picture and the context. Doctor Hickey: Anything individually doesn't necessarily mean anything. This is sort of the process of being a doctor. You take this concern that the parent or another doctor has. You take the way that the baby looks. You take the lab test results. Everything gets put together. Then you sort of take all of that data to try to figure out what you think about the situation. So, there's not sort of, "Well, what's the one thing that's important?" If you're thinking that way, that's not the way doctors think. Brenna: That's probably important when we think about care and management, because this condition can be so variable from person to person. Just knowing that you have 22q Deletion Syndrome probably doesn't say, "This is the exact treatment and management." You're probably having to look at what that specific patient needs. Doctor Hickey: Right. Yeah. That's a really good point too. Even other doctors who aren't involved in genetics, they have this idea that I can look at a report and a piece of paper and then tell them what the patient looks like. It grants me a lot of power that I don't really have. So, yes, everyone is an individual and has their own individual set of challenges. I think really always care is going to be tailored to the individual patient. Doctor Hickey: What we use, the diagnosis of 22q Deletion Syndrome, we take that at the start of a road map or these are the risks that we're aware of based on that information. These are the things that we think we need to look out for. There are certain guidelines that have been out there since 2011. Then there's whatever's going on with the patient or their family. Then we kind of either add some things or we take some things out depending on their specific situation or preferences or concerns or whatever. So, you get the diagnosis, and those guidelines are a start for what you need to do, but then you take the individual situation for sure. Brenna: With all that in mind, my next question is probably not exactly fair without speaking about an actual patient in front of you. Doctor Hickey: It's okay. Brenna: Just sort of thinking generally, if you did have that textbook fit all of the check marks 22q Deletion Syndrome patient, what would care and management look like generally? Doctor Hickey: Well, we use the guidelines from Journal of Pediatrics in 2011. So, they're always going to ... When we make the diagnosis, there is just a checklist of things that should be looked for. Really, there's no recommendation to change that based on the age of the patient. So, it's really interesting because this is the condition that may be diagnosed prenatally based on a concern on, for example, before the baby's born. It might be diagnosed right after the baby's born. Might be diagnosed in early childhood. I've seen a handful of young adults with some psychiatric challenges who are diagnosed around college age or even a little bit after that. Doctor Hickey: There's really no recommendation to sort of do the whole kit and kaboodle no matter what age somebody is. So, we're always going to recommend an echocardiogram or an ultrasound of the heart, recommend calcium testing due to concerns for difference in parathyroid activity. Always going to recommend immune system testing, renal ultrasound to look for the structure of the kidneys. Doctor Hickey: Speech and language therapy is often a very integral part of this condition, because they may have a cleft pallet, but if they don't, they still might have what's called velopharyngeal insufficiency, which is weakness of the muscles and the structures that are separating the mouth cavity from the nasal cavity. So, their voice may have this hyper nasal intonation to it that makes it difficult for others to understand them. Increasingly, that is recognized to be an issue that is, in some cases, amendable to surgical therapy. So, that might be apart of the care, having a scope that goes and looks at the function of the structures that they close off, the connection between the two cavities. So, that is usually a standard part of care as well. Doctor Hickey: We'll always tell families about the genetic inheritance of the condition. We offer testing to parents if they would like it. It's a new genetic change about 93% of the time, so it's only inherited five to seven percent of the time. So, it's usually not inherited. It's important in genetics, as you know one of our really central tenets is non-directiveness, so we offer genetic testing. We don't tell people that they have to get it or not to get it. We just explain the facts, and families can decide on their own. Brenna: It sounds like you have great guidelines and management options and even some surgical and treatment options. At this point, is there a cure for this condition? Doctor Hickey: No. Generally, put it in the groping of a chromosome condition. Another aspect of genetics is that your genetic information is present and found in all of the trillions of cells of your body. So, anything that would be considered "cure" would have to reach and have its effect and change the genetics in every one of those trillions of building blocks of your body, which is just a real challenge. Doctor Hickey: The typical deletion or missing information in 22q Deletion Syndrome includes around, depending on your definition of what a gene is, includes about 70 genes. So, you have, at least at the outset in theory, 70 genes that aren't working correctly. There may be effects on other genes that are outside the deletion. Where we are in medical science, as least as far as I understand it is, we're making some in-roads in therapies, at least targeted therapies, for the genetic difference in single gene disorders. So, where you have one gene that's not functioning properly, usually a gene that has lost a function and is not doing at all what it's supposed to do. Doctor Hickey: That's what I would consider the low hanging fruit of cures and therapies and genetics. Something like this that's a chromosomal condition is going to be many years down the line after we get the hang of single gene disorders, which we still really haven't done. Those therapies are really only available for a handful of conditions. Brenna: That's a lot of information and a lot of cells to work on. Just the last couple of questions, I know you've seen patients at a variety of ages, but in general, is there shortened life expectancy for individuals with 22q Deletion Syndrome? Doctor Hickey: Well, obviously I get asked that a lot by parents, and it's a very emotionally charged question. So, I think it's important to be kind of specific about it. If a child has a really significant structural difference in the anatomy of their heart, that is always going to effect life expectancy. So, that's true in 22q Deletion Syndrome and not in other children who don't have 22q Deletion Syndrome. Doctor Hickey: In terms of how this has been looked at, I think those are really ... I would piece people into separate buckets there the way that I thought about them. There are other things that are known to effect life expectancy just in and of themselves and by themselves, including intellectual disability and then schizophrenia. There is a substantial risk for neuropsychiatric conditions such as schizophrenia and 22q Deletion Syndrome. Although, the majority won't have that issue. So, those things effect mortality too. Doctor Hickey: Each subsequent study that I see on this, the median age of survival gets longer. So, I think that's encouraging. The last report that came out of Canada of an adult clinic, a prominent adult clinic in Toronto was that the median age of death was in the mid to late 40s, which I know is not what people want to hear. You have to understand that also includes people with significant congenital heart disease. If a child doesn't have significant congenital heart disease, I think we would expect more than that. I think with guidelines and modern medical care, I think we expect to continue to improve over time. Brenna: My final question of today is, what's one thing you would like people to leave this podcast knowing about 22q Deletion Syndrome? Doctor Hickey: Well, it's a little bit of a restatement of what we mentioned before. In genetics, I always like to bring up to other providers and families sometimes that a diagnosis isn't necessarily a prognosis. Again, I can't look at that sheet of paper and have it serve as a crystal ball for a person's future. It does, as we mentioned, offer a road map for care. I think that's why it's important to make the diagnosis so we understand what's going and we know what to look out for in the future. Hopefully if further issues are going to develop, we will catch them early and be able to make interventions and prove things by catching them early. Doctor Hickey: Again, that everyone is different. We had to learn this over many years as our technology changes that we thought we had an idea of how this condition looked and that people were all going to all develop all these problems. Then later, we developed a new test and started testing more people and then found that lots of people had it that didn't have any of those problems that we thought they should have. I think it's just important to understand that the diagnosis is not the prognosis. Brenna: Thank you, Doctor Hickey, for spending time with us today. Brenna: If you have a loved one who was recently diagnosed with 22q Deletion Syndrome, it is important that you identify physicians familiar with this condition. You can go to 22qFamilyFoundation.org to see a list of specialty clinics and find one near you. Brenna: Our final guest today is Keisha Fonnell. Keisha's son, Rowen, was diagnosed with 22q Deletion Syndrome when he was two years old after numerous visits with specialists. Thank you for joining us today, Keisha, and for sharing your story. Brenna: Why don't you start off just by telling us a little bit about yourself? Keisha Fonnell: Well, I am 36 years old. I am a mother to two beautiful children, one of which is a little extra special because he has 22q Deletion Syndrome. I think that's probably our biggest thing in our life and our family. Brenna: When you first hear 22q Deletion Syndrome, what initially comes to mind? Keisha Fonnell: A little bit of everything, fear of the unknown. Mostly we don't always know what's next with him. Then hope obviously because there's a lot of research going on right now. There's a lot of education going on right now. I didn't even know what it was before my son was diagnosed. I've been an OPN since 2004, and I had never heard of that syndrome before. I worked both in the elderly setting, and then also with children, I work with [inaudible 00:36:34]. I have seen a good many syndromes but not that one. Brenna: So, it was new information for you when you got that diagnosis? Keisha Fonnell: Very. Brenna: Let's back up a little bit. Why don't you introduce us to your son? Tell us a little bit about him. Keisha Fonnell: Okay. Well, Rowen is seven. He'll be eight real soon. He's awesome. He has got a great sense of humor. He's very loving to his family. He is mild in the respect that his cognitive abilities are much higher than I think we previously expected. He's in first grade, and he's in mainstream school. He does still have some therapies and things like that, but he's doing really well right now. Brenna: Yeah, that's great to hear. Thinking about how you got this diagnosis, when did you first become aware that your son might be different from other children? Keisha Fonnell: Well, day one of life, they told us that he had multiple heart defects. But 22q wasn't one of the screening blood tests. It should be. I would like it to be, but it wasn't. So, that was the first time we realized something was wrong. Then he wasn't able to latch. He had a lot of nasal regurgitation, a lot of reflux. I found myself taking him to a lot of specialty appointments. I would say around six months, he stopped meeting milestones. He would sit but not unless you propped him. After that, he stopped meeting his milestones and therapy started shortly thereafter. Keisha Fonnell: It was not until he was a little over two years old that we met Doctor Chalman at the AZMI Clinic. That appointment was for something else and turned into a diagnosis, which was both bittersweet because I could finally put a name to what was going on, but then at the same time you were putting a name to what was going on. That appointment was meant for, to my understanding, it was supposed to get more language therapy. The more we talked, the more he started asking me questions, the more I realized it was going in a different direction. We got the diagnosis about two weeks later. He called me on the phone. Brenna: What was that process like for you, you know, waiting to get that diagnosis? Keisha Fonnell: I believe I was in denial. That's 100%. Doctor Chalman is wonderful. He's changed our life. He was positive that the test would come back positive, and he told me that afterwards. For those two weeks or so, I was certain there was just no way. It had to be something else. It was sort of denial really. When he called me, he was wonderful. You know when you're going to get bad news and when you're going to get good news it sounds different on the phone? If it's good news, someone's just going to be like, "Hey, guess what?" That's not ... I knew. He was just like, "Are you alone? Is there someone with you? Can you sit down?" That's when I knew he was going to tell me. Keisha Fonnell: He said, "Yeah, your son has 22q Deletion Syndrome." He said, "The first thing I need you to do is go see a genetic counselor immediately." He said, "We have those resources, and we need you to talk to them right away so that you can be properly educated and we can get started." Brenna: That must have been quite some news to hear. Keisha Fonnell: Yes. It stopped us in our tracks. It was good to give a reason for all the things that was happening. Everyone kept ... Certain people were throwing around autism and things like that, and I just really didn't think that was quite what was wrong. There were other bits to it, and there were other things that were going undiagnosed that he diagnosed when we were there. That's when we realized that he had velopharyngeal insufficiency and he had a submucosal cleft pallet that no one had noticed yet. Even though we knew he had a bifid uvula, no one had realized even with the speech and everything else that was going on. Keisha Fonnell: He gave us so many diagnoses and so many things that we could go ahead and start checking off the list. That makes you feel good when you check something off the list. It's like, "Okay, moving to the next thing," and just making sure that we're doing our best for Rowen at all times. Brenna: It sounds like maybe after meeting with Doctor Chalman as well as a genetic counselor and hearing about different signs and symptoms, things started to line up with what you were seeing in your son. Keisha Fonnell: Yeah, but it was really scary. You don't know what's next. You don't know if he's going to be okay. You know there's surgeries coming up. None of these appointments are great. Everybody there is wonderful, but you don't want to have to be doing that with your kiddo. Brenna: Going through that process with it being scary, is there something you wish you would have known or heard that maybe would have made the process a little bit better for you? Keisha Fonnell: If someone could have told me that it was going to be okay when it the big part of it was over and the surgeries were over, maybe I could've been a little stronger. I think I was a good, strong mom for him, but I was scared. I would tell anybody that if you're going through something like this with your kiddo, seek out your own therapy. Be sure to validate yourself, your own feelings, your own journey, because it's important to keep yourself going so that you can be there for your child. Rowen went through a lot of things that he didn't fully understand, and I had to be the one there. So, it helps to talk to other people about that. Brenna: I think that's great advice. I think that's something more families should hear as a whole. So, once you've received your diagnosis, you started marking off those check boxes, as you were saying. What has therapy and management looked like for you and for Rowen? Keisha Fonnell: Management has looked like a lot of appointments, regular blood work. Then we sought out CHOP in Philadelphia. They have a 22q NU Department, an entire clinic that actually fully understand my child and what's been going on. The doctor there has been studying the syndrome since 1983. Her and several other doctors wrote a book that she gave me. They're full of knowledge. They're constantly researching, which they have us do like spit in a vial, things like that just so they can keep learning. Keisha Fonnell: He's had multiple surgeries. He had his cleft repaired at CHOP. That was two different surgeries a year apart. That surgeon's fabulous. There's been a lot of therapy, everything, occupational therapy, physical therapy, vision therapy, speech therapy and we do therapeutic writing. Brenna: It seems like that's a lot of appointments for you to keep up with and to make sure everyone's getting to you at a right time. Keisha Fonnell: Mm-hmm (affirmative). You have to advocate. You have to stand your ground as a mom. A lot of times, you meet a doctor who doesn't know what your child has. You actually have to start from the beginning and be like, "This is what 22q is." I've met a lot of doctors who still try to call it the DiGeorge. They'll be like, "Well, he has this, this and this." I'm like, "Well, no, actually he doesn't. It's more on the velocardial facial side. So, it was more this, this and this versus what you're talking about." It makes a big difference. They need to know that he has this before we get started with anything else. You have to understand our history. Brenna: That seems like then probably going to a place like CHOP where people already understand what's going on and have that baseline extremely beneficial. Keisha Fonnell: It was crazy to meet her for the first time, because it was almost like she knew us, and Doctor Chalman the same way. When he would start to talk to me and describe my child, even though this was literally our first appointment, it's crazy to meet someone who already knows and it's very comforting. You realize that someone else is fully aware of what's going on, and they have ideas like, "When your child's like nine, you need to have this x-ray," or, "We need to do this yearly," or, "Have you seen this doctor yet?" It's nice to have somebody who is already on the same page. Brenna: Outside of having obviously these fabulous support resources and these physicians, has there been anything else that's been super helpful for you support-wise throughout your journey? Keisha Fonnell: We use the CSIU. So, we had home therapy and we use a private therapy, KidWorks. They have been wonderful along the way. I would say that my biggest support has been my family, 100% my family. Everybody understands we're going through a journey. Everyone has helped. There's no judgment. I think my family's been the main reason we've gotten through everything really and truly. Brenna: Is there any particular organizations or support groups that you would recommend to other families who have 22q Deletion Syndrome? Keisha Fonnell: I don't even have a Facebook. So, I am not apart of any groups. I can tell you that I do 22q at the Zoo every year. I love meeting new families, whether they have a new diagnoses or they're new to the area or they traveled from somewhere. Talking with other families that are going through something similar is very therapeutic. All our stories are different, because all our kids are a little different. I would say, I mean organizations-wise, it's mostly the hospitals and therapies that we've had. Brenna: Thanks so much for spending time with us today. Just in closing, what's your best advice either to another mom or other family members who might have just found out that their child or another loved one has 22q Deletion Syndrome? Keisha Fonnell: I would tell you to take a big deep breath and strap in, because it's going to be a journey. It's going to be an adventure. As long as you have the support around you, you'll get through it. It's a journey, and you have to validate yourself and you have to advocate for your child. That's the most important. Brenna: Thank you, Keisha, for introducing us today to Rowen and sharing your story. Brenna: For many families, the diagnostic journey can be long, but don't give up. You are not alone. For additional resources and connection to other families, you can go to the International 22q Foundation website at 22q.org. Brenna: In closing, we have had the chance to talk to three experts today in 22q Deletion Syndrome, but this is just the beginning. We have taken all of today's information and included it in a free downloadable guide. You can get your free guide by going to RareDisease.com/22q. We would love to connect with you. If you need to talk to someone, we're standing by. Go to RareDisease.com/help. We are waiting for you. Rare Disease Connection is a production of Aspect Health and RareDisease.com. Thanks for joining us.

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Resolution of Primary Immune Defect in 22q11.2 Deletion Syndrome

Mahidol University

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Examining Genetic Factors That Affect the Severity of 22q11.2 Deletion Syndrome

Albert Einstein College of Medicine

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Thymus Transplantation in DiGeorge Syndrome #668

Duke University

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