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Down Syndrome


Down Syndrome

Authors: Peters Vincent J.T. & de Winter J. Peter

Down syndrome (DS), often caused by trisomy 21, is the most common form of intellectual disability among newborn infants worldwide. Differences in annual live births have been observed per continent: around 17,000 annual live births of children with DS have been estimated in Europe, around 5,100 annual live births of children with DS have been estimated in the US, and around 300 annual live births of children with DS have been estimated in Australia and New Zealand. The presence of prenatal screening and elective terminations has negatively influenced the live birth rates of children with DS.

The availability and accessibility of prenatal testing (like non-invasive prenatal testing) and genetic counselling certainly have a current and future impact on the number of live births with DS. In addition, there is a risk of the routinization of prenatal screening, where parents are no longer facilitated to make informed decisions based on their own moral and practical considerations, but family members, relatives, and friends alike, implicitly or explicitly expect that parents will choose prenatal screening, diagnostic testing, and, perhaps the termination of pregnancy. Such potential societal pressure may increase the effect of the vailability of prenatal screening on the live birth rate of children with DS. Other factors – such as religious beliefs, economics, the complexity of society, changing maternal ages, cultural beliefs, and social norms – likely play additional roles. The anticipated quality of life for a person with DS might also be an essential consideration in the decision-making for some expectant parents.

About live birth rates, the life expectancy of persons with DS has significantly increased in the last decades due to improvements in medical care, such as improvements in cardiac surgery, prevention of childhood infections, and broader access to standard care. This results in an expanding cohort of persons with DS who need medical care addressing their unique profile. Given these developments, we aimed to provide a brief overview of progress made in the last few years regarding medical comorbidities and care models in the field of DS healthcare.

Persons with DS are known to have an intellectual disability and a variety of malformations like congenital heart defects, small ears, small mouths, and other physical findings, along with medical conditions like hip dislocation and leukaemia. Many medical conditions are more common in individuals with DS than the general population and affect health, development, and daily functioning. Therefore, secondary screening for comorbidity is an essential part of the care of persons with DS. DS is associated with medical comorbidities and disorders that differ from population rates and impact organ systems throughout the body. As a result, persons with DS have an increased risk for conditions like obstructive sleep apnea, obesity, hearing problems, vision problems, congenital heart diseases, autism, regression disorder, and Alzheimer’s disease, among others. The healthcare professionals most frequently involved in treating these comorbidities are paediatricians, cardiologists, ophthalmologists, ENT physicians, dieticians, speech therapists, orthopaedic surgeons, physiotherapists, (paediatric) cardiologist, psychologist, and education generalist.

The best followup for persons with DS involves regular medical checkups, developmental assessments, and social support. Medical checkups should be scheduled every year or as recommended national guidelines to monitor any health concerns or conditions that may develop. Developmental assessments help identify learning difficulties and other developmental delays, allowing for early intervention and tailored support. Social support is essential, including education and training for family members and caregivers on how to provide persons with DS with a supportive environment where they can thrive. This deserves attention from the moment the information about a suspected DS diagnosis, either before or after birth, is communicated with family members and caregivers. Additionally, access to therapy and programs that promote social interaction, life skills, and independent living can help promote a high quality of life for persons with DS.

With declining birth rates yet a higher prevalence of childhood and adult survivors with DS, it is important to identify the optimal model to deliver care for persons with DS in all life stages. Finding the optimal model is especially relevant because although each separate clinical problem is often well known, the personal tailoring of the screening, prevention, and treatment in an individual with DS makes the organization and delivery of DS healthcare complex. Around the globe, there is significant variability in content, organization, provision, and access to care for persons with DS. They follow different models, serve different populations by age or location, and are organized by different medical specialties. This diversity hampers the implementation of personalized care and leads to unmet care needs all around the globe. For example, in the US, specialty DS clinics exist where some see only the paediatric population, whereas others provide care restricted to adults. In Europe, multidisciplinary care for children with DS is organized in various forms: in the Netherlands, paediatric outpatient clinics organize multidisciplinary team appointments, and in Israel, multidisciplinary centers provide holistic care to persons with DS. In Asia, integrated care for children with DS is realized by organizing multidisciplinary care with protocol-driven surveillance in Taiwan, and clinical guideline management by physicians in Singapore.The importance of specialty clinics is also recognized in other countries like Oman.

Although various care models have been reported in the literature, there is no evidence that one model is more effective than others. Therefore, the variety in care models should make us pause and re-consider who should care for children with DS, and how that care should be delivered and organized. First steps are made in this regard by, for example, using a modular decomposition approach to provide insight into the underlying organizational structure of healthcare provision, which provides opportunities to offer persons with DS individualized healthcare based on their needs and requirements. These first steps could eventually influence the quality of healthcare for persons with DS and, consequently, the quality of life in persons with DS.

There are several areas of investigation that could be explored to understand the long-term outcomes of persons with DS. Some potential avenues of research might include 1) Medical follow-up: persons with DS are at increased risk for a variety of medical conditions, including heart defects, thyroid disease, and Alzheimer’s disease. Studying long-term outcomes could involve tracking the incidence and progression of these conditions, as well as evaluating the effectiveness of different interventions or even medical treatments, 2) Intellectual development: long-term studies could explore the factors that contribute to intellectual development over time, as well as strategies for maximizing potential in different areas of functioning, and 3) Occupational and social outcomes: persons with DS often face employment discrimination and social isolation, despite the fact that many are capable of living independently and contributing to society.

Although DS is an incredibly complex, multi-system condition, the affected persons, their family members and caregivers, and involved healthcare professionals in both paediatric and adult care provision have an opportunity to collaborate and provide new insight into complex care delivery in the 21st century. One opportunity is actively involving persons with DS in health research, also known as inclusive health research. However, historically persons with DS have been excluded from (clinical) research and family members and/or caregivers have served as a proxy. This has proven helpful given that family members and caregivers often have more experience and expertise about their offspring, since they are in the lead of care content and organization. Hence, they face the life-long challenge of negotiating health and social service systems for these persons with DS who depend on others to understand and explain their needs. Although family members and caregivers are often used as proxies in paediatric care, differences between children and their proxies have been reported. Therefore, it might be worth exploring whether persons with DS, in addition to caregivers, could also serve as experts-by-experience in inclusive health research to capture the full potential of these persons.

Another opportunity arises concerning the transition from paediatric to adult care. This transition has many challenges, crossing all dimensions of life. Persons with DS and caregivers need to find adult healthcare providers, ensure insurance coverage, and, where possible, take ownership of their health maintenance. In parallel, transition in various other spheres, such as educational, vocational, financial, social, guardianship, and legal responsibilities. Despite the attributed importance of this transition, only a few studies have been conducted on the transition of care for persons with DS, and no consensus has been reached on the organization of care transition for persons with DS.

Last, an increasing number of persons, besides persons with DS, live with complex care needs resulting from incredibly complex, multi-system conditions. Due to lifelong care needs on multiple life domains, these persons present a challenging task for healthcare professionals and care systems to provide optimal personalized care, taking both the characteristics of the genetic disorder and the individual into account. The progress in the field of DS can be extrapolated to offer directions for dealing with complex care needs for persons with other rare genetic disorders like 22q11 deletion syndrome, Williams syndrome, and Phelan-McDermid syndrome.

The manifestations of DS are complex, warranting (ideally) expert and multidisciplinary care in all life stages. Due to lifelong care needs, persons with DS present a challenging task for health care providers and care systems all over the world to provide optimal care, taking both the characteristics of the genetic disorder as well as the individual needs into account. In the present paper, we present an overview of progress made in the last few years regarding medical comorbidities and care models in the field of DS healthcare. We hope this overview is inspiring and leads to avenues for future research.


Vincent J.T. Peters1

1Department of Management, Tilburg School of Economics and Management, Tilburg University, Tilburg, the Netherlands; Tranzo, Tilburg School of Social and Behavioral Sciences, Tilburg University, Tilburg, the Netherlands


Down syndrome is a complex congenital condition and the most prevalent genetic cause of intellectual disability in humans. Although people with Down syndrome share a typical appearance, intellectual disability, and delayed motor development, each individual with Down syndrome is unique. In addition, many individuals with Down syndrome experience various comorbidities, therefore, people with Down syndrome have complex healthcare needs. The prevalence and severity of these comorbidities varies. This makes individuals with Down syndrome a very diverse and heterogeneous patient group from an early age, despite their common genetic background (trisomy 21). Providing adequate healthcare and interventions in the early life of individuals with Down syndrome improves physical and mental development. In the Netherlands, 22 pediatric outpatient clinics organize multidisciplinary team appointments (so-called “Downteams”) to address the complex healthcare needs of children with Down syndrome. In this study, we present the healthcare provided by these multidisciplinary teams in a modular way and show that this modular approach results in improved healthcare provision for children with DS.

O H Elshazali1, H Abdullahi2

1Consultant Paediatric cardiologist, University of Khartoum, Sudan
2Consultant Obstetrician and Gynaecologist , Sidra medicine, Doha, Qatar


Down syndrome is the most common chromosomal malformation, it affects multiple organs, necessitating a need for medical care for different systems. The care needed by infants with Down syndrome is complex and needs planning and coordination at different levels. Medical services in Sub-Saharan Africa are not robust and face challenges in providing accessible and affordable health care. We will review the situation of the medical care provided to infants with Down Syndrome, looking at diagnosis, counselling, and management within the Sub-Saharan context. Exploring the challenges and suggesting recommendations.

Octavio Garcia1, Jesús Antonio Villegas-Piña1, Jesús Antonio Villegas-Piña1

1Facultad de Psicología, Unidad de Investigación en Psicobiología y Neurociencias, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, 04510, México.


Down syndrome is the most common genetic cause of intellectual disability. Nevertheless, under certain stimulation processes, Down syndrome people can develop certain intellectual skills, suggesting an active mechanism of neuronal plasticity. Defects in both dendritic arborization and dendritic spines could affect neuronal plasticity and contribute to the degree of intellectual disability in people with Down syndrome. However, the cellular mechanisms involved in this process are unknown. Thrombospondin-1 (TSP-1) is an astrocyte-secreted protein involved in the development and maintenance of dendritic spines and synapses, which is altered in Down syndrome. Nonetheless, the role of TSP-1 in neuronal plasticity is not well characterized. In this study, we analyze whether TSP-1 is involved in neuronal microstructure changes induced by environmental enrichment, a model of experience-dependent neuronal plasticity. We found that the increase in dendritic spine density induced by environmental enrichment is associated with an increase in TSP-1 levels in the hippocampus of wild-type mice. The lack of TSP-1 in TSP-1-/- mice produce changes in the number and length of dendritic branches and a decrease in both, the number of intersections and density of dendritic spines. Exposure of TSP-1-/- mice to environmental enrichment did not affect the dendritic length and branching and number of intersections, but increased the density of dendritic spines significantly. These results suggest a role of TSP-1 as an important factor regulating brain microstructural plasticity, whose activity is reduced in Down syndrome.

Miki Kosaka 1,2, Hidenobu Senpuku3, Asami Hagiwara2, Yoshiaki Nomura1, Nobuhiro Hanada1

1Tsurumi University School of Dental Medicine
2Tokyo Children’s Rehabilitation Hospital, Japan
3National Institute of Infectious Disease


Individuals with Down syndrome (DS) are known to be highly susceptible to periodontal disease, exhibiting a rapid progression and increased severity in younger age. They are also at high risk for Alzheimer’s disease (AD) with certain risk derived from amyloid-β (Aβ) accumulation. Periodontal disease in DS individuals is related to an impaired immune system, poor oral hygiene, gingival tissue abnormalities, salivary factors, microbial factors and oxidative stress with high levels of radical oxygen resulting in genetic abnormalities. However, simultaneous assessments of these factors were not performed to clear risk factors to periodontal disease in DS individuals. This study investigated relationships among various parameters in oral and systemic diseases in DS and non-DS subjects.

Thirty DS subjects and 38 non-DS subjects were enrolled in this study and their oral hygiene and oral disease status were examined. Unstimulated whole saliva and blood samples were collected to investigate the presence of periodontal bacteria, cariogenic bacteria and opportunistic pathogens; interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α saliva concentrations; and Aβ42 plasma concentrations. Among tested parameters, Aβ42 plasma concentrations, development of periodontal diseases, S. mutans rate, lactobacilli per total streptococci ratio, numbers of Candida and IL-6 and IL-8 saliva concentrations were significantly higher in DS subjects than in control subjects. Additionally, oral disease parameters, except for the decay-missing-filled index, were significantly higher in DS subjects than control subjects. However, no significant difference was observed in periodontal bacteria ratios between DS and control subjects.

Our results demonstrate that DS subjects are more likely to develop periodontal diseases, produce inflammatory cytokines and become infected by opportunistic pathogens in the oral cavity than control subjects. This is likely due to poor oral hygiene and decreased host defense responses rather than infection of pathogenic bacteria or Aβ accumulation.