DSRF was proud to host Dr. George Capone for a one day conference on Down syndrome covering topics relating to overall health and development. Working with Dr. Osman Ipsiroglu, Dr. Sylvia Stockler, Kirsten Graham and of course Dr. Capone (please refer to endnotes for associations), we planned for a day filled with information relevant to families and professionals. The conference was broken into three sections, with lots of time for questions and answers.
The three segments focused on:
Overviews: Down syndrome as a genetic disorder and a neurobiologic disorder, impact on brain development/function, behavior phenotypes, and sleep disorders
Medical: epidemiology, medical risks and screening, research data on behaviour and mental health
Interventions: basis for identifying and prioritizing targets for biomedical intervention into cognition, promoting cognitive development, enhancing established cognitive function, and preventing cognitive decline
There were many important points made during the presentation. While we cannot include them all in this brief summary, we have tried to capture those that have the most significance.
Chromosome 21 (C21) was sequenced in 2000 as part of the Human Genome Project, yet there is still no therapeutic focus. There are still huge gaps in our knowledge of the consequence of the triplicated genes on C21 which exert continuing effects across the lifespan.
C21 contains 350-500 unique genes in 3 copies, and in addition there are modifier genes that interact with C21.
A distinguishing feature of Down syndrome is the decreased number of cells in all parts of the body (i.e. this includes bone density, organs, and the brain). The opportunity for complex connectivity is reduced from the start due to fewer brain cells.
Genes (including CBS and SOD) that impact DNA synthesis, repair and cellular methylation are located on C21. This may impact an individuals’ ability to effectively metabolize folate and it is also a B12 dependent process.
Much has been done to enhance the effectiveness of prenatal testing, but little has been done to develop meaningful therapies. Suggested rational targets for prenatal and postnatal interventions include therapies that are focused on enhancing neurogenesis and cell survival to increase stable nodes upon which to build circuit complexity. These could include: transcription factors, growth factors (brain-derived neurotrophic factor), signaling molecules (sonic hedgehog) and stem cells.
“Developmental theory is a proxy for true understanding of complex events. Has this therapeutic focus resulted in real improvement or benefit? Developmentally based education, including coaching, parent training, guidance, and individualized teaching may provide benefit for some, but for others - maybe not. These are limited tools against the reality of an extra chromosome 21 in every cell of the body.”
There are recognized challenges to the Canadian model of care, where a physician or pediatrician may have only one patient with Down syndrome on their caseload. This makes it very challenging for a primary care pediatrician or general practitioner to stay on top of research and best practice information, and points to the need for a more specialized model of care with centralized resources and knowledge base.
It is very important to medically screen asymptomatic individuals, rather than only deal with issues once symptoms have surfaced. It is also important to look beyond observed behaviour for physiological causes. The updated Health Care Guidelines for individuals with Down syndrome is a good tool for families and clinicians to use, and may help to identify issues before they become a major problem. See the American Academy of Pediatrics Health Care Guidelines and the Health Watch Table for DS from Surrey Place Centre in Toronto.
Health management should be thought of as having three components: neurocognitive and mental health, weight/metabolic and restorative sleep.
Neurogenesis is involved with moving short term knowledge acquisition into long term memory, and this is negatively impacted by high stress, high cortisol levels, bad sleep and no exercise. Medications can interfere with sleep. Restless or motorically active sleep is an indication of poor quality sleep. Periodic limb movements can be a result of low levels of ferritin, which may be treated with supplements.
Good sleep is critical to the consolidation of memory and learning. Dr. Capone compared restorative sleep to syncing your iPod to your computer: “Your downloaded music and apps aren’t permanent until it has been synced!”
Obstructive sleep apnea is very common in DS. Airway factors are a bigger factor than obesity, and having your tonsils out does not protect against obstructive sleep apnea.
When learning is compromised and/or behaviour indicates poor executive function (including inhibition, cognitive flexibility and emotional control), this is a problem in frontal lobe integrity which is further compromised by illness or poor quality sleep.
There are often very complex presentations of Down syndrome with many co-occurring conditions that may be exacerbated by missed medical conditions which are likely treatable.
Some people with Down syndrome are vulnerable to impacts on executive function and mental health issues at or around puberty, and this may relate to synaptic reorganization that happens around this age for everyone.
The life span of individuals with Down syndrome has increased and there is a “tsunami of people with Down syndrome who are aging.” Statistics from the USA Centre for Disease Control show that 2/3 of people with Down syndrome in the U.S. are over age 21, and 1/3 are children.
Autism looks different in individuals with Down syndrome. This comparison was made for individuals with dual diagnosis:
Social affection is somewhat preserved (not so in autism alone)
Individuals with both DS and ASD have more issues with adaptive skills
Individuals with DS at 4.7 years and 7 years can show regression-type ASD (they experience a later onset than typically developing children)
When comparing the research funding that has been devoted to autism, Down syndrome falls woefully short.
At the end of the day we invited families and professionals to stay for a planning session to discuss development of a working group and how to address gaps in health services for individuals with Down syndrome. Advocacy, knowledge dissemination and implementation of measures to improve care for DS patient were the main topics in the final round table discussion. The absence of a specialized DS care center and the consequential gaps in long term care can be overcome by an orchestrated action plan taken by all stakeholders.
In order to start this discussion collaboratively with parents, patient advocates, health care professionals serving at all three tier service levels, as well as medical and political opinion leaders, the following action plan has been suggested:
(1) To develop a plan for dissemination of protocols among physicians and health care providers in BC, including evidence based screening for common late onset morbidities in DS;
(2) To integrate DS related competencies into graduate and postgraduate curricula and explore career paths for fellows and physicians with special interest in DS;
(3) To create a subspecialty DS clinic including pediatric and adult specialists (developmental pediatrics, psychiatry) for complex medical cases with focus on subspecialty knowledge dissemination to universal health care providers;
(4) To develop a plan for advocacy and government involvement.
Associations of Key Individuals
Osman S. Ipsiroglu, MD, FRCPC, MAS MBAPhD [Venia legendi, Medical University of Vienna]Adjunct Professor, Thompson Rivers University, KamloopsClinical Associate Professor, UBCBC Children's Hospital,Dept. of Pediatrics, Faculty of Medicinec/o Sleep Research Lab [Sunny Hill Health Center for Children]
Sylvia Stockler MD, PhD, MBA, FRCPCProfessor Pediatrics, Department Pediatrics, UBCHead Division Biochemical Diseases, BCCHProject Lead, Treatable Intellectual Disability Endeavour in BC (TIDE BC)
Kirsten GrahamParent AdvocateChildren’s Sleep Network
George T. Capone, MDDirector, Down Syndrome Clinic and Research Center,Kennedy Krieger InstituteAssociate Professor, Pediatrics,John Hopkins School of Medicine
The CKNW Orphans' Fund has granted DSRF $5,200 for our 2014 summer school programs for students with Down syndrome. Thank you for empowering individuals with Down syndrome to reach their full potential!