A Literature Review on Diseases in Down Syndrome Patients

This report provides a comprehensive literature review on the various diseases that affect the survival of individuals with Down syndrome (DS). It begins with an introduction to DS, its causes, and the increasing life expectancy of those diagnosed. The report then delves into the specific diseases associated with DS, including intellectual capacity limitations, congenital heart diseases (CHD), Alzheimer’s disease (AD), leukemia, gastrointestinal defects, thyroid disorders, and epilepsy. Each disease is discussed in detail, with references to relevant studies and research findings. The report highlights the prevalence, symptoms, and potential complications associated with each condition, emphasizing the need for further research and effective treatment strategies to improve the quality of life and survival rates of individuals with DS. The report is a valuable resource for understanding the complex health challenges faced by individuals with DS and the importance of comprehensive care.

Running head: Human Disease 1
Diseases affecting the survival of individuals with Down syndrome
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Table of Contents
1.1 Introduction..........................................................................................................................3
1.2 Features of Down’s syndrome.............................................................................................4
1.3 Diseases................................................................................................................................4
1.3.1 Intellectual capacity.......................................................................................................4
1.3.2 Congenital heart diseases (CHD)..................................................................................5
1.3.3 Alzheimer’s diseases (AD)............................................................................................6
1.3.4 Leukaemia....................................................................................................................7
1.3.5 Gastrointestinal Defects.................................................................................................8
1.3.6 Thyroid Disorders..........................................................................................................8
1.3.7 Epilepsy.......................................................................................................................10
Conclusion................................................................................................................................10
References................................................................................................................................12

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1.1 Introduction
Down syndrome (DS) is the most common disease of chromosomal abnormality in humans
and affecting approximately 1500 babies across the world, depending on the parental age, and
prenatal screening schedules (Kazemi, Salehi, & Kheirollahi, 2016). Down syndrome is the
leading cause of learning and memory problems globally and several patients across the
world undergo different additional health complications such as congenital heart diseases,
Alzheimer’s diseases, Leukaemia among others (Kazemi et al., 2016). DS is as a result of
trisomy of the entire part or a section of chromosome 21 in all or specific body cells and the
successive increase in manifestation as a result of gene dosage of the trisomic genes. There is
an increasing focus on the treatment of adults with Down’s syndrome. In the last five
decades, there has been reported an improved survival beyond the first year of life for
individuals diagnosed with DS; form less than 50% to over 90% (Wu & Morris, 2013). The
authors observed an increase in the median age at death from 25 to 49 years between 1983 to
1997 respectively, however noticeable differences have been observed in different racial and
social cohorts 8. the current life expectancy has increased to 60 years 9, with 44% of those
with DS in the UK expected to live up to 60 years and 14% to 68 years. it is expected that the
life expectancy of those aged 50 years and above will rise by 200% by 2010 (Wu & Morris,
2013).
Despite the increasing research in the diagnosis and treatment of DS, there is a corresponding
increase in the diseases that affect the survival of individuals with downs syndrome, which
further complicates the treatment of the disease. Therefore, there is the need for identifying
multiple diseases that reduce the survival chances of the people diagnosed with DS and which
further makes its treatment difficult. Regarding Robertsonian translocation, there is 2-4%

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occurrence, and in which case, the extensive arm of the chromosome 21 is connected to
another chromosome.
1.2 Features of Down’s syndrome
Several significant features are observable in all DS population, including intellectual
capability problems, congenital heart diseases, and Alzheimer’s diseases, among others
(Asim, Kumar, Muthuswamy, Jain, & Agarwal, 2015). The most prevalent cause of DS in
babies in the existence of an additional copy of chromosome 21 leading to trisomy.
Robertsonian translocation and ring chromosome or isochromosomal are other causes of DS.
Isochromosal is a condition in which two extensive arms of the chromosome get detached
together instead of the long and short arm detaching together during the development of the
egg-sperm. Trisomy is a condition which results when chromosome 21 fails to detach during
sperm or egg growth. Some of the physical symptoms of DS include a small chin, poor
muscle tone, slanted eye, small mouth and large tongue leading to protruding and a single
increase of the palm (Asim et al., 2015). Some other features include short fingers, big toe,
and irregular pattern of fingerprint among others.
1.3 Diseases
1.3.1 Intellectual capacity
Down’s syndrome is the leading cause of extreme intellectual disability, with almost
everybody diagnosed with the disease manifesting symptoms of the intellectual disability.
Several studies have examined the intellectual disabilities in DS right from birth to adulthood.
Liogier d'Ardhuy et al. (2015) carried out a research study and generated a first-time
cognitive scale to measure executive function, language and memory in DS people aged
between 12 and 30 years. The study found out that there were significant neurocognitive
changes in young and senior adults with DS when observed for six months. Hoyo et al.

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(2015) examined language problems in young adults with DS but without dementia and
found a distinct deficit in word retrieval beyond the concurrence of usual words. The
semantic verbal fluency test was significant in forecasting the risk of dementia in DS people.
In the review by Edgin, Clark, Massand, and Karmiloff-Smith (2015) to assess the ultimate
state of DS cognitive phenotypes during the period of growth, the authors found out that
language problems were much more prevalent in children with DS more than expected
bearing in mind their overall mental age. Brain imaging data show that network connectivity
is more developed in DS adults with elevated levels of local network synchrony and poor
connectivity of distant networks resulting in language problems. Additionally, the review also
found out that children and adults with DS had sleep impairments and could be very harmful
to the effective working of the memory and the learning of words.
1.3.2 Congenital heart diseases (CHD)
DS is usually associated with intellectual disability, but the disability from other related
congenital morbidity is also substantial. Children born with DS are less likely to survive up to
5 years of age (Asim et al., 2015), and for those that survive have significant health issues
alongside intellectual disability. Benhaourech, Drighil, and Hammiri (2016) conducted a
retrospective study for six years using a Paediatric unit of hospital registry and collected data
based on the presence of DS syndrome. The study aimed to assess the different elements of
association between DS and congenital heart disease (CHD). The study found out that there
were 186 incidences of CHD with atrioventricular septal disorder being the most prevalent
(29%), then ventricular septa disease (21.5%). The mortality rate for all the different forms of
heart disease was 14.1%.
Another population-based cohort study was carried out by Bergström et al. (2016) to
ascertain the developments in CHD problems in new-borns with DS. The research found out

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that 54% of all the infants were diagnosed with DS but the risk of developing congenital heart
problems declined with time. There was a significant reduction in the risk of complex
congenital heart disease by 40% in 2012 compared to 1994. On the other hand, then there was
a substantial increase in DS for isolated ventricular or atrial septal diseases in the future.
Sobey et al. (2015) carried out a population-level matched cohort study to ascertain the risk
of occurrence of the primary cardiovascular disease in individuals with DS. The authors used
hospitalization data obtained from the Australian State of Victoria. The study found out that
there was a marked increase in the prevalence of congenital heart defects in the DS group.
1.3.3 Alzheimer’s diseases (AD)
Autopsy studies indicate that the brains of most of the people diagnosed with DS and aged 40
years and above have increased levels of beta-amyloid plaques and tau tangles which depict
the presence of Alzheimer’s disease. It is reported that approximately all the people
diagnosed with DS are likely to develop Alzheimer’s disease (AD) commencing at 30 years
of age. Moreover, 70% of people with DS will develop dementia, with a corresponding
increase in the development of AD with the increase in life expectancy (Hartley et al., 2014).
Head, Lott, Wilcock, and Lemere (2016) conducted a review to highlight the existing
literature on the AD neuropathology in DS. The authors observed that the overt manifestation
of the amyloid precursor protein gene on chromosome 21 results in the initial onset of beta-
amyloid and plaques in Down’s syndrome.
The review conducted by Head, Powell, Gold, and Schmitt (2012) on the association between
Alzheimer's disease and DS and found out that clinical dementia was prevalent in individuals
diagnosed with DS and at the age of 48 to 56 years; approximately 10 years after the first
symptoms of AD development start to form. Therefore, there exists a prodromal stage in DS
when AD pathology increasingly gathers, however clinical symptoms of Alzheimer’s disease
may not appear until after 10 years or more. Head, Silverman, Patterson, and Lott (2012) also

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found out that there was a 55% incidence of AD in individuals with DS and aged between 40
to 49 years, with an incidence of 55% in those aged between 50 to 59 years.
1.3.4 Leukaemia
Maloney (2011) carried out an updated review on Acute lymphoblastic leukaemia (ALL) in
children with DS and found out that DS was the most prevalent chromosomal defect in
children and has increased frequency of acute leukaemia. The study also noted increased
morbidity linked to chemotherapy in children diagnosed with Down’s syndrome. According
to Khan, Malinge, and Crispino (2011), there is a marked decline in the occurrence of cancer
in adults with DS compared to those without the Down’ syndrome, but children with DS are
at a higher risk of being diagnosed with leukaemia. About 50% of children with leukaemia in
their tender age are categorised as acute megakaryoblastic leukaemia (AMKL). It was also
found out that the median age of the manifestation of myeloproliferative disorder (TMD) was
over 200 neonates is three to seven days. Neonates and TMD had a clinical expression of
bruising, breathing complications and even come in 15-20% of diagnosed cases. The review
also indicated that most of the leukaemia cases resolve naturally with normal blood counts at
an average of 84 days, however, after about one to four years, 30% of the DS children with
leukaemia develop acute megakaryoblastic leukaemia (Malinge &Crispino, 2011).
Similar results were obtained by Mateos, Barbaric, Byatt, Sutton, and Marshall (2015) who
found out that children with DS had a higher risk of being diagnosed with leukaemia,
especially acute megakaryoblastic leukaemia. The researchers also indicated that 30% of the
infants with DS were affected by a pre-leukemia disease known as a myeloproliferative
disorder (TMD).

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1.3.5 Gastrointestinal Defects
It has been shown by Holmes (2014) that children and adults with DS will frequently display
gastrointestinal signs such as constipation, diarrhoea, abdominal discomfort among others.
DS individuals may, however, experience structural and functional defects of the
gastrointestinal tract and associated parts. The study review found out that about 10% of
children and young adults with DS are likely to be affected by gastrointestinal disorders.
About 75% of neonates reporting to various clinics are likely to exhibit gastrointestinal
difficulties including problems with eating. DS patients make up 12% of all cases of
Hirschsprung disease (HD) which is a type of low intestinal blockade due to the lack of
normal myenteric ganglion cells in some portion of the colon. The non-existence of ganglion
cells in children with HD leads to the dysfunction of the distal intestine to relax normally. As
a result, peristaltic waves do not cross over the aganglionic part leading to no defecation and
functional blockade.
The common signs that are manifested immediately after birth include abdominal distention,
severe vomiting, and the inability to pass meconium. Newborns with duodenal atresia exhibit
severe vomiting during the initial neonatal period, and if not treated in time, will lead to
severe dehydration and imbalance in body fluid ions. IA is a birth disorder characteristic of
the deformation of the rectum and it is related with the rise of some other defects, all called as
VACTERL association (Asim, Kumar, Muthuswamy, Jain, Agarwa, 2015). According to the
research by Tabor and Alfirevic (2010), about 10 in Has 21 genes changes have been
associated with DS.
1.3.6 Thyroid Disorders
The prevalence of congenital hypothyroidism in newborns diagnosed with DS through
neonatal screening is approximately 27 times higher than the global population. In a study by
Campos, and Casado (2015) on the assessment on the oxidative stress, DS, and thyroid

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dysfunction, the authors found out that there was a 66% incidence of thyroid dysfunction in
people with DS depending on the dynamics of population size, age, laboratory tests among
others. Pierce, LaFranchi, and Pinter (2017) also conducted a retrospective review from one
school to ascertain the features of thyroid disorders in children with DS. 24% out of the 508
patients that were examined underwent a diagnosis associated with thyroid dysfunction with
most of them having increased thyrotropin cured with levothyroxine. The study projected that
50% had thyroid defects by the time they are adults, with 20% of hypothyroidism being
detected before they are six months old.
A follow-up on the status of thyroid disease in adults with DS was conducted by Prasher,
Ninan, and Haque (2011) for 15 years by carrying out yearly thyroid function tests in 200
patients. The study found out that healthy adults with DS manifested a steady increase in
thyroxin and likely steady decrease in thyroid-stimulating hormone with age. The prevalence
of definite hypothyroidism was observed to be low for the 15 years and its onset was not
obviously influenced by subclinical hypothyroidism. Similarly, Claret, Corretger, and Goday
(2013) conducted a retrospective, observational study on DS patients who had been
diagnosed with hypothyroidism before five years of age with an aim of examining the natural
evolution of Subclinical hypothyroidism to ascertain the factors that envisage its natural
remission. The authors sample 53 patients with an average age of 2.4 years and had
subclinical hypothyroidism. The findings showed that there was a 73.6% incidence of
spontaneous resolution of hypothyroidism in an average of 13.2 months. Patients diagnosed
with goitre had a substantial resolution rate (94.9%). Therefore, the study found out that
subclinical hypothyroidism which manifests itself in the newborns with DS is normally
temporal.

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1.3.7 Epilepsy
Studies have indicated an incidence of 1.4-17% of the occurrence of epilepsy in a patient with
DS 1. Barca et al. (2014) carried out a systematic retrospective analysis of the Pediatric
Neurology Clinic database for four years with the aim of assessing the relationship between
epilepsy in children with DS. 39 pediatric cases with DS and neurological signs were
identified with 23% of them being linked with epileptic seizures. The authors found out that
56% of the subjects were epileptic, with 5% of them exhibiting astatic seizures. 33% of the
subjects manifested focal seizures with 11% having eyelid myoclonias. 22% of the epileptic
and DS children had minor mental retardation and 78% had average to extreme cognitive
delay.
In contrast, a clinical-video EEG study was carried out by Vignoli et al. (2011) on epileptic
adults with DS, the average age of 46 years. The study found out that the average age for the
manifestation of epilepsy was 36.8 years with 40.9% of the subjects having focal epilepsy
and late-onset myoclonic epilepsy. Arya, Kabra, and Gulati (2011) conducted a review on the
different elements of epilepsy in DS on the basis of paediatric neurology. The study indicates
that epilepsy in DS patients is at 1-13% occurrence with the West syndrome being the most
common form of the disease in children with DS.
Conclusion
Down’s syndrome is the most prevalent chromosomal disorder in both adults and children,
but especially in newborns and is related to multiple diseases. These diseases make it difficult
for DS patients to survive. Moreover, it is significant to understand the diseases associated
with DS for effective and successful treatment of DS. Some of the most common diseases
associated with DS are an intellectual disability, congenital heart diseases, Alzheimer’s

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diseases, Leukaemia, gastrointestinal defects, thyroid disorders, and epilepsy. All these
diseases in addition to DS require careful attention and further research in order to
successfully address them and increase the survival chances of those diagnosed with Down’s
syndrome.

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References
Arya, R., Kabra, M., & Gulati, S. (2011). Epilepsy in children with Down
syndrome. Epileptic Disorders, 13(1), 1-10.
Asim, A., Kumar, A., Muthuswamy, S., Jain, S., & Agarwal, S. (2015). Down syndrome: an
insight of the disease. Journal of biomedical science, 22(1), 41-55.
Barca, D., Tarta-Arsene, O., Alice, D. I. C. A., Iliescu, C., Budisteanu, M., Motoescu, C., ...
& Craiu, D. (2014). Intellectual disability and epilepsy in down
syndrome. Maedica, 9(4), 344-355.
Benhaourech, S., Drighil, A., & Hammiri, A. E. (2016). Congenital heart disease and Down
syndrome: various aspects of a confirmed association. Cardiovascular journal of
Africa, 27(5), 287–290.
Bergström, S., Carr, H., Petersson, G., Stephansson, O., Bonamy, A. K. E., Dahlström, A., ...
& Johansson, S. (2016). Trends in congenital heart defects in infants with Down
syndrome. Pediatrics, 138(1), e20160123-e201601244.
Campos, C., & Casado, Á. (2015). Oxidative stress, thyroid dysfunction & Down
syndrome. The Indian journal of medical research, 142(2), 113–119.
Claret, C., Corretger, J. M., & Goday, A. (2013). Hypothyroidism and Down's
syndrome. International Medical Review on Down Syndrome, 17(2), 18-24.
Edgin, J. O., Clark, C. A. C., Massand, E., & Karmiloff-Smith, A. D. (2015). Building an