Our recent publications - highlights


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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