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Health and disease in adults with Down syndrome

Authors:
Eva Albertsen Malt at University of Oslo
Eva Albertsen Malt
Renate Charlotte Dahl
Renate Charlotte Dahl
Renate Charlotte Dahl
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Trine Marie Haugsand at Akershus universitetssykehus
Trine Marie Haugsand
Ingebjørg H Ulvestad
Ingebjørg H Ulvestad
Ingebjørg H Ulvestad
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Abstract and Figures

Background: The increasing life expectancy of persons with Down syndrome calls for a knowledge of conditions that frequently occur in adults with the syndrome and of which health personnel should be particularly aware. Method: The article is based on a literature search in PubMed and the authors' clinical experience with the patient group. Results: Altered immune system function, muscular hypotonia, dysmorphic otolaryngologic features and premature ageing contribute to health problems. The group is susceptible to infections, particularly of the respiratory and the gastrointestinal tract. Congenital heart defects may give rise to symptoms, also in adults. Many also develop mitral valve disease, including those without congenital heart defects. Hypothyroidism develops in up to half, and coeliac disease in one of five. Obstructive sleep apnoea syndrome occurs in approximately half. Sensorineural hearing loss and cataract may occur before the age of 30. Atlantoaxial instability occurs, and radiological examination of the neck must take place before intervention under general anaesthesia. Behavioural changes with loss of skills, withdrawal, psychomotoric retardation and mutism occur frequently from the age of 30 and may be symptoms of mental illness or the onset of Alzheimer's dementia. Interpretation: Adults with Down syndrome need to undergo regular medical examinations, and we recommend an annual check-up with the primary doctor. Screening for hearing loss and cataract is also recommended every three and five years, respectively. In the event of concomitant symptoms, particularly related to neurological and psychiatric conditions, the patient can be referred to the habilitation service.
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REVIEW ARTICLE
290 Tidsskr Nor Legeforen nr. 3, 2013; 133: 290 – 4
Review article
Health and disease in adults
with Down syndrome
290 – 4
Eva Albertsen Malt
emal@ahus.no
Renate Charlotte Dahl
Trine Marie Haugsand
Ingebjørg H. Ulvestad
Nina Merete Emilsen
Børre Hansen
Yon Eduin Galezo Cardenas
Rolf Olof Skøld
Anne Tove Berge Thorsen
Eva Merete Male Davidsen
Department of Adult Habilitation
Akershus University Hospital, Norway
MAIN POINTS
The life expectancy of persons with Down
syndrome has increased in recent years
and is now about 60
The syndrome is associated with specific
diseases and accelerated ageing processes
A number of diseases occur more frequently
or earlier in persons with Down syndrome
Regular clinical check-ups should be carried
out by the primary doctor
BACKGROUND The increasing life expectancy of persons with Down syndrome calls for
a knowledge of conditions that frequently occur in adults with the syndrome and of which
health personnel should be particularly aware.
METHOD The article is based on a literature search in PubMed and the authors' clinical
experience with the patient group.
RESULTS Altered immune system function, muscular hypotonia, dysmorphic otolaryngo-
logic features and premature ageing contribute to health problems. The group is susceptible
to infections, particularly of the respiratory and the gastrointestinal tract. Congenital heart
defects may give rise to symptoms, also in adults. Many also develop mitral valve disease,
including those without congenital heart defects. Hypothyroidism develops in up to half, and
coeliac disease in one of five. Obstructive sleep apnoea syndrome occurs in approximately
half. Sensorineural hearing loss and cataract may occur before the age of 30. Atlantoaxial
instability occurs, and radiological examination of the neck must take place before interven-
tion under general anaesthesia. Behavioural changes with loss of skills, withdrawal, psycho-
motoric retardation and mutism occur frequently from the age of 30 and may be symptoms
of mental illness or the onset of Alzheimer’s dementia.
INTERPRETATION Adults with Down syndrome need to undergo regular medical examina-
tions, and we recommend an annual check-up with the primary doctor. Screening for
hearing loss and cataract is also recommended every three and five years, respectively.
In the event of concomitant symptoms, particularly related to neurological and psychiatric
conditions, the patient can be referred to the habilitation service.
Down syndrome is the most frequently
occurring chromosomal abnormality in
humans, and in 2010 there were 69 live
births of infants with Down syndrome in
Norway (1.1 of 1 000 live births) (1). The
syndrome is due to trisomy of the whole or
part of chromosome 21 in all or some cells
of the body and is associated with mental
retardation, congenital heart defects, gastro-
intestinal anomalies, reduced neuromuscu-
lar tone, dysmorphic features of the head,
neck and airways, characteristic facial and
physical features, audiovestibular and visual
impairment and a higher incidence of other
clinical disorders (2, 3).
Thanks to medical progress, particularly
in cardiovascular surgery and cancer ther-
apy, the life expectancy of persons with
Down syndrome has increased from an aver-
age of 35 in 1982 to about 60 today (4, 5). As
a result, the health service more frequently
encounters adults with Down syndrome and
with typical health challenges. This paper
provides a brief overview of conditions that
doctors should be aware of in this patient
group.
Method
The article is based on literature identified
through search in the PubMed database with
the subject search term «Down syndrome»
and the text word «adult» combined with
each of the terms «ageing», «Alzheimer’s
disease», «autoimmune diseases», «cogni-
tive impairment», «dementia», «dermatitis»,
«endocrine system diseases», «epilepsy»,
«eye diseases», «gastrointestinal diseases»,
«health», «hearing loss», «heart», «immune
system diseases», «mental disorders», «mus-
culoskeletal diseases», «neoplasms», «ner-
vous system diseases», «obesity», «otolaryn-
gologic diseases», «periodontal diseases»,
«seizures», «sleep apnoea syndromes» and
«thyroid gland». The search was limited to
the period 2000 – 2012 and the cut-off was
April 2012. The search did not include con-
straints on study design or type of article. We
first conducted a search based on conditions
that we know from our own clinical experi-
ence frequently occur in adults with Down
syndrome. The search was refined and re-
peated with a number of search terms after
we had read articles indicating that more con-
ditions should be included. We identified 486
articles, and these were assessed on the basis
of the abstract. Empirical articles and reviews
dealing with clinical disorders in adults with
Down syndrome were read in full text
(n = 142). The search identified no meta-
analyses. The articles regarded as of most
relevance to our subject were included. Sear-
ches in the Cochrane Library and Best Prac-
tice databases did not identify any further
relevant articles. The article is also based on
the authors’ own clinical experience with the
patient group.
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Results
A number of clinical conditions occur more
frequently in adults with Down syndrome
than in the rest of the adult population
(Table 1) (6 – 24). Some conditions are asso-
ciated with specific dysmorphic features,
while others are assumed to be due to acce-
lerated ageing processes (15, 25). Anoma-
lous prevalence figures are quoted for some
conditions. This is primarily because the
evidence base consists of a few, small stu-
dies using dissimilar methods.
Cognition
Persons with Down syndrome are on aver-
age mildly to moderately mentally retarded,
equivalent to a mental age of 8 – 9 years, but
there are wide individual variations (26).
Neuropsychological tests show that many
have a cognitive profile with special weak-
ness in verbal memory and strength in sol-
ving visuospatial problems (27). The ability
to plan and change strategies is often weaker
than their mental age would imply (28).
Visual aids are more important to learning
than frequent repetition.
Fertility
Women are usually fertile, and guidance on
contraception is necessary (15). Conversely,
men with Down syndrome are usually sterile.
Mentally retarded persons are generally at
greater risk of being sexually exploited, and
counselling on behaviour and boundary-
setting may help to prevent this (29).
Cardiovascular disease
Almost half of children with Down syndrome
have a congenital heart defect, and atrioven-
tricular and ventricular septum defects consti-
tute 80 % of these (10). Some will require car-
diological monitoring as adults – for example
for mitral insufficiency, mitral stenosis,
outflow stenoses, residual shunt through sep-
tum, AV block, pulmonary hypertension and
development of heart failure (30, 31). Many
also develop mitral valve disease, including
those without congenital heart defects (9).
Arteriosclerosis
The prevalence of obesity in adults with
Down syndrome has been reported to be
31 – 47 %, and it is common to find lipid
metabolic disorders such as elevated LDL
cholesterol and triglycerides and low HDL
cholesterol (10, 32). Despite this, the preva-
lence of arteriosclerosis is lower than among
the normal population (10).
Immune-related diseases
The prevalence of immune-related diseases
is higher in Down syndrome than in the gen-
eral population (20).
Infections
Low cellular and humoral immunity results
in a high incidence of infections in persons
with Down syndrome of all ages (6, 7, 33).
Infections of the middle ear, respiratory sys-
tem and gastrointestinal tract are seen par-
ticularly frequently (7). Pneumonia and influ-
enza contribute to excess mortality in persons
with Down syndrome, and infection-related
excess mortality increases with age (34).
Thyroid disease
Down syndrome is associated with several
autoimmune diseases, and the thyroid is often
affected. The prevalence of thyroid disorders
with Down syndrome varies in the different
studies (7 – 50 %) depending on the popula-
tion and diagnostic criteria (10). There is
much to indicate that the risk increases with
age, and there do not appear to be gender-
related differences. Hypothyroidism is the
most prevalent, but the prevalence of hyper-
thyroidism is also slightly high (24). We
would recommend that thyroid function be
checked annually in all persons with Down
syndrome (Table 2) (14, 35).
Coeliac disease
The prevalence of coeliac disease in the gen-
eral population is 0.3 – 0.5 %, while the pre-
valence in persons with Down syndrome is
2.5 – 18.6 % depending on patient selection
and screening method (20, 21, 36).
Diabetes
The prevalence of type 1 diabetes has been
found to be over four times higher in persons
with Down syndrome than in the general
population (22).
Table 1 Frequently occurring disorders in adults with Down syndrome. Estimated prevalence
in per cent. Articles from which the estimates originate in right-hand column. Anomalous preva-
lence figures are due to few, small studies using dissimilar methods
Medical condition Estimated prevalence (%) Reference
Higher infection tendency 100 (6, 7)
Gastrointestinal disorders > 70 (8)
Mitral valve prolapse 57 (9, 10)
Alzheimer’s disease 50 – 70 (at age 60) (5, 9, 11)
Obstructive sleep apnoea syndrome 30 – 50 (9, 12)
Cataract 17 – 29 (13)
Mitral valve regurgitation 17 (9, 10)
Atlantoaxial instability 14 (9)
Hearing loss 12 – 72 (14, 15)
Epilepsy 12 – 46 (14, 16)
Mental disorders 11 – 30 (17, 18)
Keratoconus 8 – 10 (19)
Hypothyroidism 7 – 50 (10)
Coeliac disease 2 – 18 (20, 21)
Type 1 diabetes 4 (22, 23)
Hyperthyroidism 1 – 3 (24)
Atlantoaxial subluxation 1 – 2 (9)
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REVIEW ARTICLE
Dermatological diseases
Atopic dermatitis, vitiligo, alopecia areata,
fungal infections of the skin and nails,
seborrhoeic eczema and dry skin are more
prevalent in persons with Down syndrome
than in the general population (15, 21).
Hearing loss
Persons with Down syndrome have narrow
auditory canals, and accumulation of wax in
the external auditory canal may result is
hearing loss. Age-related sensorineural hea-
ring loss associated with Down syndrome
occurs 30 – 40 years earlier than in the general
population and is estimated to occur in
12 – 72 %, depending on the survey method
(14, 15). Regular screening every three years
is recommended by several authors (9, 35).
Visual impairment and eye diseases
Visual impairment and eye diseases such as
astigmatism, impaired accommodation, stra-
bismus, cataract and keratoconus are com-
mon (19). The first three conditions tend to
manifest themselves during childhood. Kera-
toconus occurs in 8 – 10 % and is often dis-
covered in the teens or early twenties. Age-
related cataract may develop in the twenties
or thirties. It is recommended that adults with
Down syndrome be examined by an eye spe-
cialist every five years, more frequently in
the event that disorders are found (13, 19).
Musculoskeletal diseases
Adults with Down syndrome often develop
musculoskeletal diseases such as arthritis at
a relatively early age (4).
Atlantoaxial instability
Radiological tests show signs of atlantoaxial
instability in up to 14 % of persons with
Down syndrome, and 1 – 2 % have subluxa-
tion symptoms (9). X-rays of the thoracic
spine in neutral, flexed and extended pos-
itions are indicated if patients have symptoms
that may point to this (9). Prior to inter-
vention under general anaesthesia, X-ray
scans of the neck of patients with Down syn-
drome should always be taken as standard
procedure.
Osteoporosis
Down syndrome appears to be a specific
vulnerability factor for the development of
osteoporosis, and both general and compres-
sion fractures of the spine occur frequently
(4). Contributory factors may be low muscle
tone and strength, limited physical activity
and autoimmune conditions. Solberg et al.
recommend bone density measurement for
women early in the menopause (35).
Obstructive sleep apnoea
Persons with Down syndrome have many
risk factors that make them prone to ob-
structive sleep apnoea syndrome, such as
abnormalities in the head, throat and respira-
tory system, overweight and hypothyroidism
(12). One small clinical study found a higher
incidence of severe obstructive sleep apnoea
with hypoxaemia, hypoventilation and frag-
mented sleep in adult patients with Down
syndrome than in subjects without the syn-
drome (37).
Gastrointestinal diseases
Abnormal developments in the enteric ner-
vous system are associated with Down syn-
drome and gastrointestinal complications can
be found in over 70 % (8). In adults, gastro-
intestinal reflux, dysphagia, obstipation, diar-
rhoea, gallstones, achalasia and pathological
liver function tests occur most frequently.
The prevalence of Hirschsprung’s disease is
elevated, and is found in 2 – 15 %, compared
to about 0.15 % in the general population.
Periodontal disease
Gingivitis and periodontitis, often immune-
conditioned, are more common in persons
with Down syndrome, and we recommend
biannual dental check-ups (9, 35).
Neoplasms
The incidence of cancer in persons with
Down syndrome has a distinctive profile
with a strongly elevated risk of certain types
of leukaemia in young children (38). There
is also an elevated risk of testicular cancer in
men with Down syndrome, and a number of
authors recommend annual palpation of the
testicles (20, 35). However, persons of all
ages with Down syndrome have been found
to have a lower risk of solid tumours (34,
38). The mechanisms behind this have not
yet been fully determined.
Central nervous system disorders
Epilepsy The incidence of epilepsy increa-
ses from an estimated 2 – 6 % in childhood to
12 – 46 % in those aged over 50 (37). The
onset of seizures appears to have a triphasic
distribution, with frequent onset in early
childhood, the third decade and after the age
of 50 (16). About half of the epilepsy cases
are partial and half are generalised. Senile
myoclonic epilepsy is the most common
type in adults (39). Late-onset seizures are
attributed to neuropathological changes as
Table 2 Recommended routine medical follow-up of adults with Down syndrome. The recom-
mendations have been drawn up by the authors, but are based largely on the booklet Diagnosing
and treating persons with retardation and dementia (Norwegian text) (35) from the South-Eastern
Norway Regional Health Authority (Helse Sør-Øst). The booklet contains a Norwegian adaptation
of recommendations from the International Association for the Scientific Study of Intellectual
Disability (IASSID), WHO and the Ageing and Health, Norwegian Centre for Research, Education
and Service Development
Time interval1Medical assessment Comment
Every six months Dental health
Annual Behavioural change
Nutrition Recording of weight and weight change
Gastrointestinal symptoms
Cardiopulmonary symptoms Auscultation
Assess need for ECG, echocardiography
and referral to cardiologist
Cardiological monitoring of congenital
heart defect
Hearing Annual clinical assessment
Audiological examination every three
years
Testicular cancer Palpation annually
Metabolism Check TSH and T4-values annually
Vision Annual clinical assessment
Specialist examination every 5 years
Other supplementary tests Test fasting glucose, haematology, SR,
CRP, liver and kidney function tests, B12,
folic acid, serum iron, ferritin, lipid
status, calcium/phosphate, vitamin D
Other Atlantoaxial instability X-ray of neck before general anaesthesia
Osteoporosis Measurement of bone density early
in menopause
General screening tests Adhere to common national guidelines
1 In the event of abnormal findings, check-ups must be more frequent and scheduled individually
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with Alzheimer’s disease. The choice of
treatment depends on the type of seizure and
epilepsy syndrome and is a task for specia-
lists.
Mental disorders
Since Langdon Down (1828 – 96) described
the syndrome in 1866, there has been a com-
mon perception that persons with Down
syndrome have a friendly, amiable personal-
ity (40). Studies confirm good general social
skills with social understanding commensu-
rate with mental age and a special ability to
imitate gestures and mimic (41, 42). Persons
with Down syndrome appear to develop
behavioural and emotional problems less
frequently in their childhood and adole-
scence than persons with other causes
of intellectual disability. From the age of
20 – 30 however, a growing incidence of
anxiety and depression is found, with sym-
ptoms such as withdrawal, mutism, psy-
chomotoric retardation, subdued moods,
passivity, loss of appetite and sleeping dis-
orders (11). Hallucinations associated with
serious depressions are not unusual. Obses-
sive-compulsive disorders with retarded
movement, tics and freeze responses occur
relatively frequently, particularly in women.
Bipolar disorders and schizophrenia, on the
other hand, appear to occur relatively sel-
dom in persons with Down syndrome. How-
ever, there is a relatively high incidence, in
women in particular, of unspecified psych-
oses characterised by a low level of aggres-
sion, but a high level of visual and auditory
hallucinations (40). At the same time, per-
sons with Down syndrome often have a
strong imagination which makes it difficult
to distinguish fantasies from hallucinations
(43). Other signs of psychosis in patients
with Down syndrome are withdrawal,
mutism and retarded movement, a sympto-
matology similar to that of depression.
Because of their greater susceptibility to
disease and generally shorter life expec-
tancy, persons with Down syndrome often
experience that close friends and fellow
members of collectives die. An intense fear
that their parents will die is not uncommon
either. Complicated grieving processes may
ensue, followed by prolonged helplessness,
anxiety and depression. Good psychological
preparation and support are important for
preventing this.
Alzheimer’s disease
Studies have shown that almost all persons
with Down syndrome have developed
neuropathological changes with amyloid
plaque and neurofibrillary tangles by the age
of 35 – 40 (5). The changes are most pro-
nounced in the frontal lobes and medially in
the temporal lobes. This can most likely
explain changes in spatial orientation, lan-
guage, speech and social interaction which
are frequently seen in persons over the age
of 30 with Down syndrome. The first signs
of incipient dementia with Down syndrome
are often a change in behaviour, as opposed
to the normal population, where reduced
short-term memory is the most common
initial symptom (44).
Women with Down syndrome undergo
menopause earlier than women in the nor-
mal population, and menopause is found to
be correlated with age at the onset of Alzhei-
mer’s disease (45, 46). A number of drugs
are used to delay the development of Alzhei-
mer-type dementia in the normal population,
but there are few controlled studies of the
effect on persons with Down syndrome. In a
recently published study in which 21 per-
sons with Down syndrome and severe cog-
nitive impairment were randomised to either
treatment with donepezil for 24 weeks or a
placebo, a significant improvement in gen-
eral and mental function was found in the
intervention group (47). However, in a study
with a similar design and 52 weeks of treat-
ment with memantine, no effect could be
identified (48).
Concluding remarks
Primary care doctors and other health per-
sonnel who meet adult persons with Down
syndrome must be aware of the special
health problems that this group is prone to.
We believe there is a need for regular exami-
nations with the most common disorders in
mind (Table 2), (9, 14, 35). Persons with
Down syndrome are followed up and treated
in the ordinary primary and specialist health
service. Those needing long-term, coordin-
ated services have a right to take part in the
scheme with an individual plan to ensure
integrated, coordinated and individually
tailored services. Patients with extensive
and complex needs can be referred to the
habilitation service. This applies particu-
larly when a change in performance and
behaviour gives rise to suspicion of a central
nervous system disease.
Eva Albertsen Malt (born 1955)
Senior consultant, associate professor and
specialist in psychiatry with special expertise
in neuropsychiatry.
The author has completed the ICMJE form
and reports no conflicts of interest.
Renate Charlotte Dahl (born 1945)
Senior consultant, specialist in neurology
and psychiatry with special expertise in neuro-
psychiatry and epileptology.
The author has completed the ICMJE form
and reports no conflicts of interest.
Trine Marie Haugsand (born 1957)
Senior consultant, specialist in neurology with
special expertise in epileptology and habilita-
tion.
The author has completed the ICMJE form
and reports no conflicts of interest.
Ingebjørg H. Ulvestad (born 1954)
Senior consultant, specialist in child and
adolescent psychiatry with special expertise
in neuropsychiatry.
The author has completed the ICMJE form
and reports no conflicts of interest.
Nina Merete Emilsen (born 1971)
Psychologist and specialty registrar in neuro-
psychology.
The author has completed the ICMJE form
and reports no conflicts of interest.
Børre Hansen (born 1966)
Specialist in clinical neuropsychology.
The author has completed the ICMJE form
and reports no conflicts of interest.
Yon Eduin Galezo Cardenas (born 1975)
Psychologist and specialty registrar in clinical
habilitation.
The author has completed the ICMJE form
and reports no conflicts of interest.
Rolf Olof Skøld (born 1953)
Psychology specialist.
The author has completed the ICMJE form
and reports no conflicts of interest.
Anne Tove Berge Thorsen (born 1961)
Specialist in clinical habilitation psychology.
The author has completed the ICMJE form
and reports no conflicts of interest.
Eva Merete Male Davidsen (born 1966)
Specialist in neurology with special expertise
in adult habilitation. Head of the Department
of Adult Habilitation.
The author has completed the ICMJE form
and reports no conflicts of interest.
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Received 30 March 2012, first revision submitted
26 August 2012, approved 20 December 2012.
Medical editor Merete Kile Holtermann.
© Opphavsrett Tidsskrift for Den norske legeforening.
Ettertrykk forbudt. Lastet ned fra www.tidsskriftet.no 22.5.2013
... As people with learning disabilities grow older, they may experience the same age-related eye conditions as the rest of the population such as presbyopia (which can be corrected with bifocal or multifocal spectacles), cataracts, which if detected can be treated surgically, or sight threatening conditions such as age-related macular degeneration and glaucoma. In people with Down syndrome these age-related changes may happen up to 20 years earlier (Malt et al., 2013). ...
A review of the evidence that people with learning disabilities experience eye health inequalities: What policies can better ensure an equal right to sight?
Article
  • Jan 2024
Background People with a learning disability experience challenges accessing primary health care services, including eye care services. Methods Eye care needs of people with a learning disability, and how well they are met by existing services in England, were explored. Barriers and enablers to accessing these services were investigated. This was informed by a scoping review of the literature and a historic literature library. Findings Adults with a learning disability are 10 times more likely than other adults to have a serious sight problem and children with learning disabilities are 28 times more likely. There is good evidence of high levels of unmet eye care need special schools in England with over 4 in 10 children attending having no history of any eye care. Conclusion The authors discuss possible systemic changes to address these inequalities in England. These include automatic entitlement to an NHS sight test annually, specialist pathways in community opticians, eye care services in special schools, and peer to peer and peer to professional promotion of services by people with lived experience. Dedicated care pathways have improved uptake of services in other areas of primary care. Research into the effectiveness of lived experience eye health advocacy is needed.
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... It occurs every year in about 1 in 1000 babies born. [8][9][10] Dental Findings 7 : ...
Dental Management of Children with Special Health Careneeds: A Review
Article
Full-text available
  • Oct 2020
Children with special needs for health care (SHCN) management causes uncertainty and anxiety amonghealth practitioners like dentists as it involves advanced skills gained through special training, enhancedunderstanding, accommodative measures and resources. A quest was undertaken to find revised and evidencebased guidelines and alternatives for the dental care available to SHCN children. Such guidelines will helpdentists determine some suitable dental treatment and also help other medical practitioners recognize the needto ensure good oral health for children with SHCN and the value of collaboration with dental practitioners.
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... [41][42][43][44][45][46] It is the common genetic cause of intellectual disabilities worldwide and encounter various additional health issues. [47][48][49] One hundred twenty-eight (12%) children came with identified risk factors. Miscellaneous and non-specific problem noted in 64(6%) and 32(3%) children respectively (Table-2). ...
Socio-demographic and Clinical Profile of Children with Neurological Disability Attending in Child Development Centre of Dr
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Full-text available
  • Dec 2023
Background: Neurological disability relatively common in children and has been increasing over recent years. This study was done to find out the socio-demographic and clinical profile of children with neurological disability attending in Child Development Centre (CDC) of Dr. M R khan Shishu Hospital and Institute of Child Health (ICH).
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... It is characterized by trisomy of the chromosome 21 in 95% of the cases, with the remaining 5% being attributable to translocations and/or mosaicisms. 1 Patients with DS also present a wide variety of comorbidities, including congenital heart defects, recurrent infections, hearing impairment, thyroid abnormalities, overweight, and neuropsychiatric conditions such as autism and epilepsy, impacting their quality of life. 2 The World Health Organization (WHO) defines quality of life as an individuals' perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns". It is a wide concept that includes physical and psychological health, level of independence, and social relationships. ...
Quality of life in Down syndrome in Brazil: a cross-sectional study
Article
Full-text available
Background Down syndrome is the most commonly genetic cause of developmental delay and intellectual disability, affecting 1:700 live births. It is associated with heart disease and recurrent infections, among other complications that greatly impair the patient's quality of life. Objective To evaluate the major factors associated with quality of life in a cohort of patients with Down syndrome. Methods We assessed 1,187 patients with Down syndrome, older than 4 years old, with an adaptation of the Personal Outcomes Scale validated for Portuguese language, interviewing patients, parents, and caregivers. Results A bad quality of life was reported in 56.4% of the sample. The main factors associated with better quality of life were female sex, first medical visit before 4 months old, higher parental education, a professionally active mother, and prenatal care. The main factors associated with worse quality of life were family history of alcohol abuse and psychiatric disorders and comorbidity with autism and epilepsy. Conclusion Clinical comorbidities such as autism and epilepsy carry a heavy burden among patients with Down syndrome, while factors related to family support, such as employment status and educational background of the parents, enhance quality of life. The factors associated with quality of life among patients with Down syndrome should be adequately evaluated in medical consultation and targeted in public health policies.
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... One of the most frequent congenital birth defects is Down syndrome (DS). It is also one of the common genetic causes of mental retardation with complex clinical spectrum of variable features affecting various human organs [1] that occurs in approximately one per 1000 babies born each year [2]. It was described in detail by John Langdon Down in 1866 [3] and identified by French researchers in 1959 [4]. ...
Homologous Anatomical-Based Facial-Metrics Application to Down Syndrome Face Recognition
Article
Full-text available
  • Jan 2023
Down syndrome (DS) is one of the prominent neuro-developmental diseases which are distinguished by atypical fractionation behaviors, physical traits, and other mental disabilities. Current techniques of recognizing the syndrome need genetic testing through clinical studies, which is usually expensive and challenging to get. In order to simplify the classification approach, computer-aided facial analysis methods incorporating machine learning and morphometrics are crucial. Thus, this study proposes Homologous Anatomical-based Histogram of Oriented Gradients plus Support Vector Machine (HAB-HOG/SVM) to automatically detects and extracts 74 homologous facial landmarks from the subjects (DS patient and healthy control) face image and Chord-Transformed Principal Components (CT-PC) as features extraction method for classification. The novelty of this method relies on the automatic acquisition of landmark data which is conceptually simple, robust, computationally efficient, and annotation error-free and the feature extraction technique applies which is simplified enough to follow. The experiment reports recognition accuracy of 56.82% and 98.86% for Classical Principal Components (CPC) and Chord-Transformed PC, respectively. The results demonstrate that the suggested method outperformed not only the CPC but also the previously presented state-of-the-art methods in the domain of DS face recognition.
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Hypothyroidism is a causal determinant of age-related cataract risk in European population: a Mendelian randomization study
Article
Full-text available
  • Feb 2024
Objective To determine whether there is a causal relationship between thyroid dysfunction and the risk of age-related cataract (ARC) in the European population. Design A two-sample Mendelian randomization (MR) study. Methods Hypothyroidism, hyperthyroidism, free thyroxine (fT4), and thyrotropin (TSH) were selected as exposures. The single nucleotide polymorphisms (SNP) of hypothyroidism and hyperthyroidism were obtained from the genome-wide association studies (GWAS) of the IEU database, including 337,159 subjects. Data for fT4 and TSH (72,167 subjects) were extracted from the ThyroidOmics Consortium. ARC was used as the outcome. The SNPs associated with ARC were selected from a GWAS of 216,362 individuals in the FinnGen database. The main method used was the inverse variance-weighted method, together with four complementary methods. Sensitivity analyses were performed using Cochran’s Q test, MR-PRESSO, MR-Egger regression and leave-one-out test. MR pleiotropy was used to test for pleiotropy. MR Steiger test was used to test for the directionality. Results Two-sample MR analysis revealed a positive association between genetically predicted hypothyroidism and risk of ARC (OR = 2.501, 95% CI: 1.325-4.720; P = 0.004). Hyperthyroidism, circulating fT4 and TSH levels did not have a significant causal effect on ARC (P > 0.05). The results were robust and reliable, and no horizontal pleiotropy was found after sensitivity analyses. In the MR Steiger test, we found no reverse causal effects of hypothyroidism on the ARC (P <0.001). Conclusions Our study provides strong evidence that hypothyroidism is a causal determinant of ARC risk.
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Islamic Learning Methods: Strengthening Analysis of Psychological Aspects of Down Syndrome
Article
Full-text available
  • Dec 2023
The current research is crucial in order to foster inclusive Islamic education for children with Down syndrome as well as address their psychological well-being. This study aimed to investigate diverse Islamic education methods suitable for children with Down syndrome while emphasizing the importance of educators employing Islamic teaching strategies. This research employed a qualitative approach and the Systematic Literature Review (SLR) method to evaluate the intersection of Islamic learning methods and Down Syndrome. The published papers discussed in this study were obtained using the Publish or Perish 8 software. The papers must be published within the five-year timeframe between 2018 and 2023 with the keywords "Islamic Learning Methods" and "Down Syndrome." The search of papers resulted in the discovery of 222 articles discussing Islamic methods, and only 16 were specific to Down Syndrome, with only four of them addressing the application of Islamic teaching methods for individuals with Down Syndrome. The findings of this study highlighted teaching strategies such as On-Task Conduct, Imitation, Discriminative Usage of Objects, and Word Recognition. The study identifies three main learning strategies for students with Down syndrome: the Talaqqi wa Musyafahah, Quran therapy, and Islamic Full Communication methods. This study concluded the necessity for further research on modified educational approaches that effectively support the learning and well-being of children with Down syndrome within the context of Islamic education.
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Physiological Mechanisms That Impact Exercise Adaptations for Individuals With Down Syndrome
Article
  • Dec 2023
  • J STRENGTH COND RES
Post, EM, and Kraemer, WJ. Physiological mechanisms that impact exercise adaptations for individuals with Down syndrome. J Strength Cond Res 37(12): e646–e655, 2023—Down syndrome (DS) is the most common chromosomal disorder diagnosed in the United States since 2014. There is a wide range of intellectual severities, with the average IQ of individuals with DS at approximately 50 and adults without intellectual delay at approximately 70–130. Individuals with DS vary from mild to severe cognitive impairment, depending on the phenotypic penetration on the 21st chromosome, with the average cognitive capacity equivalent to a cognitive functioning of an 8- to 9-year-old child. To have successful health, all aspects of health must be considered (i.e., overall health, fitness, and social). Both aerobic training and resistance training (RT) are favored for a healthy lifestyle. Resistance training specifically can help improve motor function and overall activities of daily living. Although many motivational and environmental barriers for individuals with DS can make exercising difficult, there are many ways to overcome those barriers (both intrinsically and extrinsically). Individuals with DS should strive for 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise a week or a combination of both. The individual should also strive for 2 or more days a week of strengthening activities, such as RT, involving all muscle groups. These activities will help improve many aspects of life, leading to a better quality of life. Regular group exercise activity can help increase self-confidence and success socially in life. This review will focus on the underlying biological mechanisms related to DS, their influence on exercise, and the roles exercise plays in mediating positive health, physical fitness, and social lifestyle outcomes.
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Comprehensive health care for children and adolescents with congenital disorders: The impact of the COVID-19 pandemic on care
Chapter
Full-text available
  • May 2023
Congenital anomalies are structural or functional changes that occur during intrauterine life. Approximately one in five deaths in the neonatal period are due to birth defects in Latin America and the Caribbean. There are several factors for their development, from infections, maternal nutritional status, use of medication, and environmental or genetic factors. Most anomalies are present in low-income countries where we have an inadequate prenatal context, a greater predisposition to infections due to precarious health, and the use of prohibitive substances (medicines and drugs) during pregnancy. From this, we have that several social determinants of health such as social, economic, cultural, ethnic, psychological, and behavioral factors influence the course of a disease in a certain population. When there is a system that integrates health care for children and adolescents with congenital disorders, including genetic syndromes, especially Down syndrome, care for children promotes better growth and development. A comprehensive health care service for children and adolescents inserted in a university hospital must be able to coordinate care actions. During the years 2020 to 2022, health services faced the covid-19 pandemic that the entire population experienced. There was an impact with a reduction in the number of daily visits to these patients and a reduction in the inclusion of new ones, leading to fragmentation or discontinuity of care.
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Polymorphisms in HSD17B1: Early Onset and Increased Risk of Alzheimer's Disease in Women with Down Syndrome
Article
Full-text available
  • Mar 2012
Background/Aims. Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). In women with Down syndrome, we examined the relation of polymorphisms in hydroxysteroid-17beta-dehydrogenase (HSD17B1) to age at onset and risk of AD. HSD17B1 encodes the enzyme 17β-hydroxysteroid dehydrogenase (HSD1), which catalyzes the conversion of estrone to estradiol. Methods. Two hundred and thirty-eight women with DS, nondemented at baseline, 31-78 years of age, were followed at 14-18-month intervals for 4.5 years. Women were genotyped for 5 haplotype-tagging single-nucleotide polymorphisms (SNPs) in the HSD17B1 gene region, and their association with incident AD was examined. Results. Age at onset was earlier, and risk of AD was elevated from two- to threefold among women homozygous for the minor allele at 3 SNPs in intron 4 (rs676387), exon 6 (rs605059), and exon 4 in COASY (rs598126). Carriers of the haplotype TCC, based on the risk alleles for these three SNPs, had an almost twofold increased risk of developing AD (hazard ratio = 1.8, 95% CI, 1.1-3.1). Conclusion. These findings support experimental and clinical studies of the neuroprotective role of estrogen.
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Intellectual disability, sexuality and sexual abuse prevention: A study of family members and support workers
Article
Full-text available
  • Mar 2012
  • AUST FAM PHYSICIAN
People with intellectual disability experience difficulty forming intimate relationships and are prone to sexual exploitation and abuse. This study sought information from people involved in the care of adults with intellectual disability regarding how they supported them in the areas of sexuality, relationships and abuse prevention. Semistructured interviews and focus groups were held with 28 family members and paid support workers caring for adults with intellectual disabilities. Interviews and focus groups were audio recorded, transcribed, coded and analysed qualitatively. Major themes emerging included views on sexuality and intellectual disability, consent and legal issues, relationships, sexual knowledge and education, disempowerment, exploitation and abuse, sexual health and parenting. People with intellectual disability were described as lonely, disempowered and vulnerable to abuse. The sex industry, internet and mobile telephones were identified as new forms of risk. While this study looked at the views of both family members and support workers, the sample was too small to identify any meaningful differences between the two groups.
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Healthcare and guidelines: A population-based survey of recorded medical problems and health surveillance for people with Down syndrome
Article
Full-text available
  • Jun 2011
  • J INTELLECT DEV DIS
Medical problems are described in a population of persons with Down syndrome. Health surveillance is compared to the recommendations of national guidelines. Case records from the specialised and primary healthcare and disability services were analysed. A wide spectrum of age-specific medical and surgical problems was described. Congenital heart defects and middle ear infections were mostly experienced by younger people, while thyroid disease, epilepsy, and Alzheimer's disease were frequent among older people. Psychiatric disorders and behavioural problems were frequent in all age groups. Health surveillance remained insufficient, despite the guidelines available. A joint effort by healthcare and disability service providers is required to ensure that the medical needs of people with Down syndrome are adequately met across their entire lifespan. An active provision of healthcare and monitoring for this vulnerable group is needed.
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Impairment of circulating endothelial progenitors in Down syndrome
Article
Full-text available
  • Sep 2010
  • BMC MED GENOMICS
Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome. Circulating endothelial progenitors of Down syndrome affected individuals were isolated, in vitro cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of CXCL12 gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis. We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells. Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.
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Memantine for dementia in adults older than 40 years with Down's syndrome (MEADOWS): A randomised, double-blind, placebo-controlled trial
Article
  • Feb 2012
  • LANCET
Prevalence of Alzheimer's disease in people with Down's syndrome is very high, and many such individuals who are older than 40 years have pathological changes characteristic of Alzheimer's disease. Evidence to support treatment with Alzheimer's drugs is inadequate, although memantine is beneficial in transgenic mice. We aimed to assess safety and efficacy of memantine on cognition and function in individuals with Down's syndrome. In our prospective randomised double-blind trial, we enrolled adults (>40 years) with karyotypic or clinically diagnosed Down's syndrome, with and without dementia, at four learning disability centres in the UK and Norway. We randomly allocated participants (1:1) to receive memantine or placebo for 52 weeks by use of a computer-generated sequence and a minimisation algorithm to ensure balanced allocation for five prognostic factors (sex, dementia, age group, total Down's syndrome attention, memory, and executive function scales [DAMES] score, and centre). The primary outcome was change in cognition and function, measured with DAMES scores and the adaptive behaviour scale (ABS) parts I and II. We analysed differences in DAMES and ABS scores between groups with analyses of covariance or quantile regression in all patients who completed the 52 week assessment and had available follow-up data. This study is registered, number ISRCTN47562898. We randomly allocated 88 patients to receive memantine (72 [82%] had DAMES data and 75 [85%] had ABS data at 52 weeks) and 85 to receive placebo (74 [87%] and 73 [86%]). Both groups declined in cognition and function but rates did not differ between groups for any outcomes. After adjustment for baseline score, there were non-significant differences between groups of -4·1 (95% CI -13·1 to 4·8) in DAMES scores, -8·5 (-20·1 to 3·1) in ABS I scores, and 2·0 (-7·2 to 11·3) in ABS II scores, all in favour of controls. 10 (11%) of 88 participants in the memantine group and six (7%) of 85 controls had serious adverse events (p=0·33). Five participants in the memantine group and four controls died from serious adverse events (p=0·77). There is a striking absence of evidence about pharmacological treatment of cognitive impairment and dementia in people older than 40 years with Down's syndrome. Despite promising indications, memantine is not an effective treatment. Therapies that are effective for Alzheimer's disease are not necessarily effective in this group of patients. Lundbeck.
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Down syndrome and the enteric nervous system
Article
  • Aug 2008
Down syndrome (DS) is the most common chromosomal abnormality occurring in humans. Up to 77% of DS children have associated gastrointestinal (GI) abnormalities, which may be structural or functional in nature. Functional disturbances may, in turn, affect the outcome of corrective surgical procedures, prompting to caution. It is becoming clear that the processes affecting the enteric nervous system (ENS) in DS not only affect the micro-anatomy but also nerve function, and there is some histological evidence of ENS variations in both human and DS animal models. This suggests that developmental disorders of the ENS are probably fundamental to the functional GI disturbances encountered in patients with DS. The anomalous brain development, function and resulting intellectual impairment associated with DS appears to result from the genetic imbalance created by the trisomy of chromosome 21. The possible links between the brain, GI and ENS involvement are not as yet entirely clear. Neurotropic factors affecting brain development during embryogenesis are probably interlinked with ENS development, but the precise mechanism of how this occurs has yet to be established. This study explores what is known about the ENS dysfunction in DS and reviews the possible importance of chromosome 21 located and other genes in its etiology. Functional motor disturbances of the esophagus and colon are not uncommon and may be congenital or acquired in nature. The most prominent of these include esophageal dysmotility syndromes (e.g. achalasia, gastroesophageal reflux, dysphagia) as well as a higher incidence of chronic constipation and Hirschsprung's disease (HSCR) (2-15%) occurring in association with DS. Chromosome 21 itself is thought to be the site of a modifier gene for HSCR. Recently identified candidate genetic mechanisms provide unique insights into the genetic background of the neurological and cognitive disorders associated with DS. Although the role of the triplicated chromosome 21 and genetic dosage remain important, the additional role of other chromosome 21 genes in the etiology of ENS developmental anomalies remains undetermined and requires ongoing research.
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Donepezil Significantly Improves Abilities in Daily Lives of Female Down Syndrome Patients with Severe Cognitive Impairment: A 24-Week Randomized, Double-Blind, Placebo-Controlled Trial
Article
  • Jan 2011
Down syndrome (DS) patients share certain neuropathological features with Alzheimer disease patients. A randomized, double-blind, placebo-controlled study was performed to investigate the efficacy and safety of donepezil, an Alzheimer disease drug, for DS patients. Twenty-one DS patients with severe cognitive impairment were assigned to take donepezil (3 mg daily) or a placebo for 24 weeks, and evaluated for activities in daily lives by concisely modified International Classification of Functioning, Disability and Health (ICF) scaling system. ICF scores significantly increased without any adverse effects in the donepezil group in comparison to those in the placebo control. Among the individual functions tested, there was a dramatic improvement in the global mental functions and in specific mental functions. Donepezil may effectively and safely improve overall functioning of DS patients with severe cognitive impairment.
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Health Conditions Associated with Aging and End of Life of Adults with Down Syndrome
Article
  • Dec 2010
  • Int Rev Res Ment Retard
Expectations for the life course of individuals with Down syndrome (DS) have changed, with life expectancy estimates increasing from 12 in 1949 to nearly 60 years of age today (Bittles & Glasson, 2004; Penrose, 1949). Along with this longer life expectancy comes a larger population of adults with DS who display premature age-related changes in their health. There is thus a need to provide specialized health care to this aging population of adults with DS who are at high risk for some conditions and at lower risk for others. This review focuses on the rates and contributing factors to medical conditions that are common in adults with DS or that show changes with age. The review of medical conditions includes the increased risk for skin and hair changes, early onset menopause, visual and hearing impairments, adult onset seizure disorder, thyroid dysfunction, diabetes, obesity, sleep apnea and musculoskeletal problems. The different pattern of conditions associated with the mortality of adults with DS is also reviewed.
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Is the good-imitator-poor-talker profile syndrome-specific in Down syndrome?: Evidence from standardised imitation and language measures
Article
  • Oct 2010
The emergence of the Down syndrome (DS) behavioural phenotype during early development may be of great importance for early intervention. The main goal of this study was to investigate the good-imitator-poor-talker developmental profile in DS at preschool age. Twenty children with Down syndrome (DS; mean nonverbal mental age NMA 1 y10m) and 15 children with non-specific mental retardation (NS-MR; mean NMA 1 y11 m) participated in this study. The Preschool Imitation and Praxis Scale (PIPS) and the Dutch version of the MacArthur–Bates Communicative Development Inventories (N-CDI) were used to determine absolute and relative (contrasted to a nonverbal mental age reference) imitation and language abilities. Results revealed that there was clear evidence for a good-imitator-poor-talker profile in preschoolers with DS. However, only the advanced bodily imitation ability seems to be syndrome-specific. Clinical implications of these findings are considered.
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Clinical outcome in Down syndrome patients with congenital heart disease
Article
  • May 2010
  • CIR CIR
Long-term complications of Down syndrome patients with congenital heart disease are poorly known. We carried out a retrospective study of Down syndrome patients with congenital heart disease and patients with atrioventricular septal defect with and without Down syndrome. Between 2004 and 2008, 317 patients with congenital heart disease were followed-up in the Adult Congenital Heart Disease Unit. Of these patients, 19 (6%) with a mean age of 26.8 +/- 8.1 years had Down syndrome. Atrioventricular septal defect was the most frequent congenital heart disease(63%) followed by ventricular septal defect (26%). Ten patients (53%) were operated on during childhood. Three of these patients required reoperation during adulthood (two patients due to left ventricle outflow tract obstruction and one patient due to left atrioventricular valve insufficiency). Four patients (21%) had Eisenmenger syndrome with improvement of functional class in those treated with bosentan, two patients (10.5%) had bacterial endocarditis and two patients (10.5%) died. No significant differences were seen in left atrioventricular valve insufficiency between atrioventricular septal defect in patients with and without Down syndrome (1.5 +/- 0.9 vs. 1.7 +/- 0.8, p = 0.689). Left atrioventricular valve insufficiency and left ventricle outflow tract obstruction were the most frequent long-term complications requiring surgical reintervention in patients with atrioventricular septal defect.
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