Our recent publications - highlights


Adult-onset obstructive sleep apnea and pediatric pharyngoplasty in 22q11.2 deletion syndrome
Cancelliere S, Heung T, Fischbach S, Klaiman P, Bassett, AS
Sleep Medicine Volume 104, Pages 49-55, 2023
DOI: 10.1016/j.sleep.2023.02.010

Obstructive sleep apnea (OSA) is a disorder which causes the airways to narrow or temporarily collapse during sleep, preventing proper breathing. This research aimed to find out how common OSA is, and what features it is associated with. Among 387 adults with 22q11.2 deletion syndrome (22q11.2DS), 73 had an overnight sleep study. More than half of these 73 individuals were diagnosed with OSA, and the age at diagnosis was relatively young (33.6 years old on average). Thus, at least 1 in 10 adults with 22q11.2DS had OSA.

Velopharyngeal dysfunction (VPD) is a condition in which the velopharynx (the back of the palate and the throat) cannot close the space that connects the mouth and the nose, and pharyngoplasty is a common surgery to repair it in children with 22q11.2DS. Our team found that pharyngoplasty in childhood may increase the risk of developing OSA as an adult. Older age, heavier body weight, and asthma also increased risk of OSA in 22q11.2DS. Men and women were equally likely to have OSA, but severe OSA was more common among men.

The gold standard for treating OSA is using a continuous positive air pressure (CPAP) machine, which provides air flow through a mask on the person’s face to keep the airway open. Most of our study participants who had OSA (including those with intellectual disabilities and/or managed psychiatric conditions) were able to use a CPAP machine regularly while sleeping, showing that OSA is treatable in adults with 22q11.2DS.

OSA is a serious condition which can lead to higher blood sugar levels, higher blood pressure, and weight gain. Our research demonstrates the need for greater awareness of OSA among adults with 22q11.2DS, which may promote earlier diagnosis and treatment. Our findings also highlight the need for long-term research on the effect of childhood surgeries, such as pharyngoplasty, on health outcomes in adulthood.

Updated clinical practice recommendations for managing adults with 22q11.2 deletion syndrome
Boot E, Óskarsdóttir S, Loo JCY, Crowley TB, Orchanian-Cheff A, Andrade DM, Arganbright JM, Castelein RM, Cserti-Gazdewich C, de Reuver S, Fiksinski AM, Klingberg G, Lang AE, Mascarenhas MR, Moss EM, Nowakowska BA, Oechslin E, Palmer L, Repetto GM, Reyes NGD, Schneider M, Silversides C, Sullivan KE, Swillen A, van Amelsvoort TAMJ, Van Batavia JP, Vingerhoets C, McDonald-McGinn DM, Bassett AS.
Genet Med. 25(3): 100344, 2023.
DOI: 10.1016/j.gim.2022.11.012.

This set of clinical practice guidelines are developed for the care of individuals 18 years and older, covering life from the transition into adulthood all the way to the elderly age range. The emphasis is on periodic assessments to uncover and manage conditions that are later-onset or previously undetected.

Early diagnosis and treatment are important, and standard treatment strategies apply for each condition.. Healthcare providers from different specialties need to provide coordinated care and tailor the management to suit the individual, taking into account coexisting issues, intellectual disabilities, learning disabilities, mental health problems, and the changing nature of 22q11.2DS over time. In many cases, family members and caregivers continue to be an essential part of the care team.

Updated clinical practice recommendations for managing children with 22q11.2 deletion syndrome
Óskarsdóttir S, Boot E, Crowley TB, Loo JCY, Arganbright JM, Armando M, Baylis AL, Breetvelt EJ, Castelein RM, Chadehumbe M, Cielo CM, de Reuver S, Eliez S, Fiksinski AM, Forbes BJ, Gallagher E, Hopkins SE, Jackson OA, Levitz-Katz L, Klingberg G, Lambert MP, Marino B, Mascarenhas MR, Moldenhauer J, Moss EM, Nowakowska BA, Orchanian-Cheff A, Putotto C, Repetto GM, Schindewolf E, Schneider M, Solot CB, Sullivan KE, Swillen A, Unolt M, Van Batavia JP, Vingerhoets C, Vorstman J, Bassett AS, McDonald-McGinn DM.
Genet Med. 25(3): 100338, 2023
DOI: 10.1016/j.gim.2022.11.006.

This set of clinical practice guidelines focuses on the care of individuals from birth to 18 years of age. The emphasis is on periodic assessments and family-centered care.

Early diagnosis and treatment as well as preventive management are strongly recommended as they optimize health, functioning, and quality of life. Healthcare providers need to have basic knowledge about the variable, multi-system, and changing nature of 22q11.2DS. Specialists from various disciplines need to provide coordinated care and tailor the treatment to suit the child. Family members and caregivers are an essential part of the care team and benefit from information and support.

Prenatal screening and diagnostic considerations for 22q11.2 microdeletions
Blagowidow N, Nowakowska B, Schindewolf E, Grati FR, Putotto C, Breckpot J, Swillen A, Crowley TB, Loo JCY, Lairson LA, Óskarsdóttir S, Boot E, Garcia-Minaur S, Cristina Digilio M, Marino B, Coleman B, Moldenhauer JS, Bassett AS, McDonald-McGinn DM.
Genes (Basel). 14(1):160, 2023
DOI: 10.3390/genes14010160.

Many babies with conditions associated with 22q11.2DS require urgent medical attention at birth or soon afterwards. Early diagnosis can help provide the best after-birth care, which is especially important for newborns who have critical heart defects, but can also help those with more subtle health issues avoid a lengthy search for a definitive answer.

This article provides prenatal guidance for: (1) families with no history of 22q11.2DS; (2) prospective parents who have 22q11.2DS themselves; and (3) unaffected couples who already have a child with 22q11.2DS. There is discussion about methods of obtaining samples for prenatal genetic screening and testing, as well as physical features that may be seen on imaging. There is explanation about what each testing method can and cannot detect, and the importance of genetic counselling.

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Hypertriglyceridemia in young adults with a 22q11.2 microdeletion.
Blagojevic C, Heung T, Malecki S, Ying S, Cancelliere S, Hegele RA, Bassett AS.
European Journal of Endocrinology 187:91-99, 2022
doi: 10.1530/EJE-21-1104

  • Triglycerides are a type of lipid (fat). Your body stores and releases energy as triglycerides in fat cells.
  • Hypertriglyceridemia means having too high a triglyceride level in the blood.
  • Hypertriglyceridemia increases the risk of:
    • Obesity
    • Diabetes
    • Heart disease
  • Our team performed a study of 7,060 non-diabetic Canadian adults to see what factors could predict hypertriglyceridemia.
    • Age range: 17 to 69 years old
    • 267 of the 7,060 adults have 22q
  • Main findings:
    • Predictors of hypertriglyceridemia:
      • 22q11.2 deletion
      • Being male
      • Certain ethnic groups
      • Older age
    • NOT a predictor of hypertriglyceridemia:
      • Use of antipsychotic medication
    • 75% of the individuals with 22q who have hypertriglyceridemia are under 40 years of age.

The 22q11.2 deletion may be a risk factor for a high triglyceride level. Nevertheless, we can lower the triglyceride level with exercise / activity, and with eating and drinking fewer sugars & simple starches. Here’s to healthy eating!

Schizophrenia Risk Mediated by microRNA Target Genes Overlapped by Genome-Wide Rare Copy Number Variation in 22q11.2 Deletion Syndrome
Ying S, Heung T, Zhang Z, Yuen RKC, Bassett AS
Front Genet 13:812183, 2022.
doi: 10.3389/fgene.2022.812183.

Approximately 1 in 4 individuals who carry a 22q11.2 deletion develop schizophrenia. In this study, we proposed that the increased risk and variable expressivity associated with the deletion may be driven by miRNA dysregulation acting together with additional genome-wide rare copy number variations. Results demonstrate convergence of this mechanism with cellular pathways implicated by previous schizophrenia genetic studies. This study helps explain the vastly increased risk for schizophrenia associated with the 22q11.2 deletion and reveals insights that may be generalizable to schizophrenia in the general population.

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Estimate of the contemporary live-birth prevalence of recurrent 22q11.2 deletions: a cross-sectional analysis from population-based newborn screening [Full text]
Blagojevic C, Heung T, Theriault M, Van L, Tomita-Mitchell A, Chakraborty P, Kernohan K, Bulman DE, Bassett AS
CMAJ Open, 2021, 9 (3) E802-E809
doi: 10.9778/cmajo.20200294

In this study, our team screened for 22q deletions in just over 30,000 babies born in Ontario between January 2017 and September 2018, in order to determine the live birth prevalence of 22q. We found 14 newborns with confirmed 22q deletions in the sample, which corresponds to an estimated live birth prevalence of 1 in 2148 live births. To put this number into perspective, cystic fibrosis and severe combined immunodeficiency (two of the genetic conditions that are screened for in Ontario’s existing Newborn Screening program) in fact have lower prevalence rates than that of 22q. We also found that the babies with 22q likely to have younger mothers, were smaller in size for their gestational age, and had lower TREC levels, which can be a marker for immunodeficiency. These results support the importance of early 22q diagnosis (either prenatally or in infancy through newborn screening), which would allow for earlier screening and management of features associated with 22q.

Sexual knowledge and behaviour in 22q11.2 deletion syndrome, a complex care condition
Palmer LD, Heung T, Corral M, Boot E, Brooks SG, Bassett AS
Journal of Applied Research in Intellectual Disabilities (pages 1–10), e-published 21 July 2021 ahead of print
doi: 10.1111/jar.12927

There is limited information about sexual knowledge and behaviours in adults with complex care needs, including those with 22q11.2 deletion syndrome (22q), which represents a group predisposed to intellectual disabilities. Individuals with intellectual disabilities have sexual needs just like other people, but they may not know as much about sex, sexuality, and sexual health. Just like the general population, individuals with intellectual disabilities may behave in ways that put them at risk of negative health outcomes, including unplanned pregnancies and sexually transmitted infections. High-risk sexual behaviours are important to identify, as the potential outcomes associated with some behaviours are not only important in themselves, but could have significant impacts on pre-existing medical and psychiatric conditions (common in adults with 22q).

To our knowledge, our team conducted the first study of sexual knowledge and behaviour in 67 adults with 22q. We found that adults with 22q, with and without intellectual disabilities or identified sexual health knowledge deficits, were engaging in sexual activities, and sometimes including high-risk sexual activities with others. We conclude that there is a need to increase preventative sexual health measures (e.g. STI screening and cancer prevention), provide a safe, sex-positive space for sexual health discussions, repeated education and counselling in certain areas. etc. in order to have the potential to reduce overall burden of disease and help improve overall quality of life in adults with 22q.

Within-family influences on dimensional neurobehavioral traits in a high-risk genetic model
Fiksinski AM, Heung T, Corral M, Breetvelt EJ, Costain G, Marshall CR, Kahn RS, Vorstman JAS, Bassett AS.
Psychological Medicine, (pages 1–9), e-published 14 January 2021 ahead of print

Adults with 22q11.2 deletion syndrome (22q11.2DS) show a wide range of expression in most features, including those related to the nervous system. In this study, researchers looked at whether the variability of features in unaffected parents might help explain some of the differences among individuals who have a spontaneously occurring (non-inherited) 22q11.2 deletion. They found that within each family, the 22q11.2 deletion has by far the largest effect on the intellectual functioning of the person with 22q11.2DS but the IQ scores also have a relationship to the IQ scores of the unaffected parents. This parent-offspring relationship is similar to what has been observed in the general population for IQ, and was present even after accounting for any effects of schizophrenia. On the other hand, the researchers did not find that there was any significant relationship between the parents’ social or motor functioning and the social or motor functioning of the person with 22q11.2DS, suggesting that other, non-shared factors may play a role for these traits.

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22q11.2 microdeletion and increased risk for type 2 diabetes
Van L, Heung T, Malecki SL, Fenn C, Tyrer A, Sanches M, Chow EWC, Boot, E, Corral M, Dash S, George SR, Bassett AS
EClinicalMedicine - The Lancet, 2020 (published online)

In our current study, we studied the possible effect of 22q on the risk of type 2 diabetes (T2D). For 314 adults with 22q, we were able to compare data to similar data from a survey of 11,874 Canadian adults. We found that individuals with 22q were more likely to develop T2D compared to the general population, even when we took into account other risk factors for diabetes, like older age, obesity, medications, and family history of diabetes. Also, the average age at diagnosis of diabetes was younger in adults with 22q. This new knowledge means that we are changing when we start to monitor for diabetes in 22q. This will allow us to put in place measures to help prevent diabetes!

Please see page 11 of our Clinic’s 2020 Newsletter for an interview with Dr. Sarah (Voll) Malecki.

Personalized medical information card for adults with 22q11.2 deletion syndrome: An initiative to improve communication between patients and healthcare providers
Loo JCY, Boot E, Corral M, Bassett AS.
J Appl Res Intellect Disabil. 2020;33:1534–1540.
doi: 10.1111/jar.12747

Many adults with 22q11.2DS and their family members have a hard time providing crucial information to those who try to help. To solve this problem, our Clinic has been offering personalized medical information cards for patients. As we reported in this article, card users have found the card to be useful in multiple ways. They provide necessary information, speed up interactions with professionals, and help avoid repeat storytelling. If you would like to obtain an electronic copy of the article, please send your request to 22q@uhn.ca. Thank you.

A genetic model for multimorbidity in young adults.
Malecki SL, Van Mil S, Graffi J, Breetvelt E, Corral MG, Boot E, Chow EWC, Sanches M, Verma AA, Bassett AS.
Genetics in Medicine 22:132-141, 2020

To study the burden of illness in 22q, we compared young to middle-aged adults with 22q to a large community-based Canadian general population sample of over 25,000 people. We defined burden of illness (“multi-morbidity”) as using five or more prescription medications. In the 25-44 year age group the overall burden of illness was most similar to the burden in the general population at age 65. In the 45-64 year age group the burden of illness in 22q was about twice that of the general population. For younger adults, the pattern tended to be consistent with the conditions commonly associated with 22q, but in middle age in 22q the pattern looked more similar to older age groups of the general population. Our results highlight the importance of providing multidisciplinary and person centred care for adults with 22q.

Please see page 11 of our Clinic’s 2020 Newsletter for an interview with Dr. Sarah (Voll) Malecki.

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All-cause mortality and survival in adults with 22q11.2 deletion syndrome
Van L, Heung T, Graffi J, Ng E, Malecki S, Van Mil S, Boot E, Corral M, Chow EWC, Hodgkinson KA, Silversides C, Bassett AS. Genet Med. 21(10):2328-2335, 2019.
doi: 10.1038/s41436-019-0509-y

As information is limited on long term outcomes in 22q, we studied mortality and survival in 309 adults with 22q and their 1014 unaffected parents and siblings. The results showed that the probability of survival to age 45 years was approximately 95% for those with no major congenital heart defect, and 72% for those with a major heart defect. Although the 22q11.2 deletion and more severe forms of congenital heart defects contribute to a significantly lower life expectancy than family-based expectations, a substantial minority of individuals with 22q had outlived both parents. The average age at death was approximately 5 years older than the age we reported 10 years ago for the initial subgroup of 100 patients with 22q.

Neurocognition and adaptive functioning in a genetic high risk model of schizophrenia
Fiksinski AM, Breetvelt EJ, Lee YJ, Boot E, Butcher N, Palmer L, Chow EWC, Kahn RS, Vorstman JAS, Bassett AS.
Psychol Med. 49(6):1047-1054, 2019.
doi: 10.1017/S0033291718001824.

The results of this study showed the average relative cognitive strengths and weaknesses in 22q (e.g., relatively better on tasks related to visual than verbal memory, and better yet when given hints). The best overall performance for adults with 22q was in Daily Living Skills. Older age was significantly associated with better functional outcomes. Executive Performance (tasks requiring more abstract thinking and judgment) was significantly associated with functional outcome. The fact that there was substantial variability between individuals emphasized the need to recognize and balance individual capabilities and environmental demands in day-to-day situations.

22q11.2 deletion syndrome-associated Parkinson’s disease.
Boot E, Bassett AS, Marras C.
Movement Disorders Clinical Practice 6:11-16, 2019

This paper reviewed what is known so far about the hallmark motor symptoms and neuropathology of Parkinson’s disease. Typical findings are present in individuals with 22q who develop Parkinson’s disease, often at a young age (average 40 years). 22q11.2DS associated Parkinson’s disease accounts for about half of 1% of all individuals with early-onset Parkinson’s disease. Studying Parkinson’s disease in people with 22q could help us understand the mechanisms that cause this condition in the general population.

Low prevalence of substance use in people with 22q11.2 deletion syndrome.
Vingerhoets C, van Oudenaren MJF, Bloemen OJN, Boot E, van Duin EDA, Evers LJM, Fiksinski AM, Breetvelt EJ, Palmer LD, Vergaelen E, Vogels A, Meijer C, Booij J; Genetic Risk and Outcome of Psychosis (GROUP) investigators, de Haan L, Swillen A, Vorstman JAS, Bassett AS, van Amelsvoort TAMJ
British Journal of Psychiatry, 3:1-7, 2019

The results of this study suggested that patients with 22q are at decreased risk for substance use and substance use disorders compared to individuals in the general population. Drinking, smoking, and drug use however are major health problems for some individuals with 22q, requiring active treatment and prevention measures.

Neurobiological perspective of 22q11.2 deletion syndrome
Zinkstok JR, Boot E, Bassett AS, Hiroi N, Butcher NJ, Vingerhoets C, Vorstman JAS, van Amelsvoort TAMJ.
Lancet Psychiatry. 6(11):951-960, 2019.Epub 2019 Aug 5.
doi: 10.1016/S2215-0366(19)30076-8.

This review paper summarizes what we know about disorders common in 22q that involve the brain. These include intellectual disability, schizophrenia, attention-deficit disorder, anxiety disorders, seizures, and Parkinson’s disease. Learning more about them in people with 22q may help scientists understand better these same conditions in the general population.

Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot
Reuter MS, Jobling R, Chaturvedi RR, Manshaei R, Costain G, Heung T, Curtis M, Hosseini SM, Liston E, Lowther C, Oechslin E, Sticht H, Thiruvahindrapuram B, Mil SV, Wald RM, Walker S, Marshall CR, Silversides CK, Scherer SW, Kim RH, Bassett AS.
Genet Med. 2019 Apr;21(4):1001-1007.
doi: 10.1038/s41436-018-0260-9.

See the UHN Newsroom article

Studying adults who were born with major heart defects (“blue babies”), but who did not have 22q, we discovered a new pathway to these important conditions. We used the most advanced genetic sequencing methods available and carefully examined for changes to genes that were likely to cause problems with the development of the heart. The findings focussed on a signalling mechanism that may be important for many individuals, including those with 22q.

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Neuropsychiatric expression and catatonia in 22q11.2 deletion syndrome: an overview and case series
Butcher NJ, Boot E, Lang AE, Andrade D, Vorstman JA, Bassett AS
American Journal of Medical Genetics A (pages 1-14), 2018, e-published 19 May 2018

Catatonia is a set of symptoms that include abnormal involuntary movements and behaviours that sometimes occur in individuals with psychiatric conditions like schizophrenia and depression and in some neurological diseases. In this study, the authors provide an overview of the psychiatric and neurological symptoms and conditions associated with catatonia in adults with 22q. The results may help with the diagnosis of catatonia so that effective treatment can be provided as early as possible.

Elucidating the diagnostic odyssey of 22q11.2 deletion syndrome
Palmer LD, Butcher NJ, Boot E, Hodgkinson KA, Heung T, Chow EWC, Guna A, Crowley TB, Zackai E, McDonald-McGinn DM, Bassett AS
American Journal of Medical Genetics A 176:936-944, 2018
doi: 10.1002/ajmga.38645

Individuals with 22q are often undiagnosed for years because this condition is not easily recognizable. This study analyzed the time it took for a diagnosis of 22q and reasons for delays across age and groups in Toronto and Philadelphia. Problems with the palate and heart were associated with shorter times to a 22q diagnosis. Non-European ancestry lead to longer times. There is a great need for education about 22q so that the condition is more widely known.

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