NBHS1304 Pathophysiology Assignment: Genetic Disorder and Disability

This essay provides an in-depth analysis of Down syndrome, a genetic disorder characterized by an extra copy of chromosome 21. The essay explores the genetic basis of Down syndrome, including the role of trisomy 21 and its impact on gene expression. It discusses the physical development of children with Down syndrome, highlighting common phenotypic characteristics such as flattened face, small head, and congenital heart defects, neurological disorders, and GI abnormalities. The essay also examines the psychological development of children with Down syndrome, addressing cognitive abilities, mental health issues, and the importance of early interventions like speech and language therapy. The essay emphasizes the need for a multidisciplinary approach to care, including physical therapy, special education, and genetic counseling to support individuals with Down syndrome and help them live purposeful lives. The essay covers the various risk factors, diagnostic techniques, and treatments for Down syndrome, providing a comprehensive overview of the disorder and its implications.

Running head: GENETIC DISORDER AND DISABILITY
GENETIC DISORDER AND DISABILITY
Name of the student:
Name of the university:
Author note:

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Introduction:
With the global burden of disease, intellectual disability has emerged as one of the
leading cause of premature morbidity around the globe. Down syndrome is considered as the
leading cause of intellectual disability that contributed to a range of other health issues such as
leukemia, neurological disease, congenital heart diseases, difficulties in attention and analysis.
Smith, Næss and Jarrold (2017), suggested that individuals with Down syndrome are affected by
a range of phenomenon resembles other chronic genetic diseases which make it challenging for
the researchers to understand the direct link between genetic factors and phenotypes.
Considering the global statistics, according to the world health organization, the approximate
incidences of Down syndrome is 1 in 1000 individuals where the United States has emerged as
the country with the highest incidence of Down syndrome (Kazemi, Salehi and Kheirollahi,
2016). While the limited study had conducted in Malaysia regarding Down syndrome, the recent
statistics suggested that in Malaysia, 1 out of 981 individuals are suffering from Down
syndrome. The majority of individuals with Down syndrome have an extra copy of chromosome
21 which resulted in phenotypic changes amongst patients. Zahari et al. (2016), suggested that
trisosomy21 occurs due to failure of chromosome separation during e gametogenesis that
resulted in the extra chromosome. Consequently, infants with Down syndrome experience
intellectual, developmental or neurological disabilities that hindered them to live a healthy and
purposeful life. While the occurrence of other autosomal trisomy is more frequent compared to
the 21, but the postnatal survival rate is low for other autosomal trisomies as compared to Down
syndrome. The essay aims to provide an in-depth analysis of Down syndrome as a genetic
disorder, the impact of disease order on the physical, developmental and psychological
development of the children in the following paragraphs.

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Discussion:
Explanation of the selected genetic disorders among children:
While a range of intellectual disabilities observed amongst children, Down syndrome has
been chosen for this essay. Antonarakis (2017), suggested that Down syndrome is considered as
a genetic disorder of infants where trisomy of 21 observed that resulted in altering gene
expression. A range of hypothesis related to the genetic basis of Down syndrome and the
association of phenotypes was presented by different researchers. While few researchers
hypothesized that a genetic dosage imbalance resulted in an increased dosage of Hsa21 and gene
expression, other researchers hypothesized that genetic imbalance amongst the children was
formed by diverse trisomy gene and influence the expression of many genes (Antonarakis et al.,
2017). However, the common hypothesis for the developing Down syndrome is multiple critical
genes play a crucial role where DSCR on 21q21.22 is accountable for various clinical
manifestation of Down syndromes amongst the children. Playas (2017), highlighted that
chromosome 21 is the smallest human chromosome which contains approximately 200 to 300
genes. The genetic basis of Down syndrome is that three cryptogenic forms of trisomy 21
resulted in clinical features of a down syndrome such as free trisomy, Robertsonian translocation
trisomy 21 and mosaic trisomy. The genetic abnormality observed amongst children when high
gene expression of genes of trisomy 21 resulted in overexpression in cells and tissues of the
children with Down syndrome. Consequently, children with Down syndrome exhibit
phenotypical abnormalities. The reproductive biology suggested that Down syndrome observed
when a part of chromosome 21 attached to another chromosome during the process of
translocation (Santoro et al., 2017). In the very early development of foetal the formation of 21
trisomies is highly prevalent. The affected individuals usually have two normal copies of 21

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chromosomes along with another 21 chromosomes attached to any of the normal copy. On the
other hand, limited population exhibit mosaic 21 where few chromosomes of cells carry trisomy
21 compared to other normal chromosomes. The molecular biologist suggested that partial
duplication of Down Syndrome Critical Region (DSCR) within 21q22 is responsible for the
development of the Down syndrome.
Figure: down syndrome ( trisomy 21)
Source: (Antonarakis et al., 2017).
Carozza et al. (2016), suggested that the frequent risk factors for Down syndrome
include advanced maternal age, first born with Down syndrome, family history of Down
syndrome and carrying the genetic translocation for Down syndrome. Advancing maternal age is
considered as the most common risk factors for the Down syndrome amongst offspring since
older eggs are at high risk of undergoing improper genetic division (Kazemi, Salehi and
Kheirollahi, 2016). Therefore, the children with Down syndrome and associated abnormal
phenotypes conditions can inherit Down syndrome from the unaffected parents. The extra-

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chromosomal copy resulted in changes of development and abnormal physical features of the
Down syndrome which would be discussed in details in the following paragraphs. Vicic et al.
(2017), suggested that during pregnancy, the high risk of Down syndrome diagnosed by
analysing the foetal sample using various invasive techniques such as amniocentesis, invasive
chorionic villus sampling and laboratory techniques such as conventional cytogenetic analysis
(karyotype), Multiplex Ligation Probe Assay and Quantitative Fluorescence-Polymerase Chain
Reaction and array Comparative Genomic Hybridization. On the other hand, non-invasive
techniques for diagnosing Down syndrome include cell-free foetal DNA screening from the
sample of maternal plasma. Van Schendel et al. (2017), suggested that since the children with
Down syndrome experience poor motor function and speech and language problem, most
common treatment of the Down syndrome is a multidisciplinary approach to the care such as
physical therapy for the motor skills, increased muscle strength along with speech therapy for
communication skills. Special education for intellectual disabilities is usually offered to the
children with Down syndrome so that they can live a purposeful life. Genetic counselling in
Down syndrome is another crucial treatment for children with Down syndrome.
Discussion on problems related to the physical development of the genetic disorder:
As discussed above Down syndrome amongst children resulted in developmental
difficulties and psychological difficulties. This section will discuss abnormalities in the physical
development of genetic disorders. Vicic et al. (2017), discussed by the children with Down
syndrome has specific physical development compared to other children. The common
phenotypic characteristics of the children with Down syndrome include a flattened face, small
head, upward slanting eyelids, and unusual shape of ears, reduced muscle tone, broad and
shorthand, short height, tiny white spots on the iris. Rupela et al. (2016), suggested that patients

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with Down syndrome usually have poor motor skills (gross and fine motor skills), poor muscle
strength and abnormal posture. Moreover, due to anatomical differences in the mouth, the
children with Down syndrome often have a high arched palate, low muscle tone in the tongue
and small jaw. Therefore, this physiological development resulted in difficulties in
communication and speech, feeding and swallowing. In this context, Rvachew and Folden
(2018), suggested that speech and language therapy would be effective interventions for the
children and adolescents with a down syndrome which will facilitate communication and speech.
Congenital heart defect:
On the other hand, Bergström et al. (2016), suggested that congenital heart defect
amongst the children with Down syndrome is one of the leading cause of mortality and
morbidity. The worldwide incidence of congenital heart defect amongst the children with
Down syndrome is approximately 50% which resulted in mortality and morbidity. The
researchers suggested that mutation of the non-Hsa21 CRELD1 gene is thought to be the
contributing factor behind congenital heart defect which further emerged as ventricular septal
defect and Secundum atrial defect. These cardiac defects are common amongst the patients from
the Asian countries such as Malaysia, India, China and few countries of Latin America.
Neurologic Disorders and Musculoskeletal Disorders:
Head et al. (2018), suggested that children with Down syndrome usually experience
neurological disorder like Alzheimer's and fast aging compared to the children with two copies
of chromosome 21 since Amyloid precursor protein is encoded on Hsa21. The possible reason
can be a direct correlation between reduced brain volume (cerebellum and hippocampus) and
Trisomy of Hsa21. On the other hand, due to trisomy 21, they have learning disabilities and low
IQ. They usually exhibit hypotonia due to the delayed motor development which resulted in

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decreased gait stability and patients and decreased bone mass (Boutot & DiGangi, 2018). They
also have vitamin deficiency D deficiency and joint dislocation. It increased the possibility of
seizures or infantile spasms which can be reduced by providing patients with anti-epileptics. The
myoclonic seizure is also common for the patients, however, it is most common amongst the
adult’s patients.
Endocrinological Disorders:
Aversa et al. (2018) , suggested that children with Down’s syndrome usually have
Thyroid gland dysfunction which resulted in hypothyroidism or autoimmune thyroid-associated
diseases. In the case of autoimmune disease of the children with Down syndrome, anti-thyroid
autoantibodies usually observed which gradually increased after a few years.
Aversa et al. (2016), suggested that children with Down syndrome have other endocrinological
issues along with thyroidal dysfunctions. They usually have difficulties in pubertal development
such as female child may experience primary hypogonadism whereas a male child may
experience cryptorchidism.
Visual abnormalities:
Postolache (2019), suggested that children with Down syndrome usually have visual
abnormalities since trisomy 21 affected the optic nerve. The researchers suggested that distinct to
refraction, the optic discs seem smaller or frequently mal-inserted which resulted in the visual
abnormalities amongst in the children with Down syndrome. Optic disc hypoplasia along with
numerous titling due to genetic abnormalities may reduce the vision of the children. However,
these factors cannot be major contributors of vision abnormalities in such children and patients.
GI Abnormalities:

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Due to structural difficulties of mouth to anus, frequent Gastrointestinal (GI) Tract is also
prevalent amongst the children with Down syndrome. Duodenal and small bowel stenosis are
also common amongst patients with Down syndrome (Boutot & DiGangi, 2018).
Discussion on psychological development of the genetic disorder:
Whitney et al. (2019), suggested that children with Down syndrome display marked
differences in cognitive abilities and skills. In the majority of cases, both genetic factors, as well
as environmental factors, contribute to these differences. A range of literature suggested that
children, as well as adults with Down syndrome, experience major psychological issues during
their life span (Kinnear et al., 2018). Children and adults with multiple health difficulties
experience a higher rate of mental health problems compared to children and adults with limited
health difficulties due to Down syndrome. The children with Down syndrome experience
inattentive behaviours, impulsive, and generalized anxiety disorders (Ilhan et al. 2019). Due to
trisomy 21 development, neurological and cognitive issues are highly prevalent amongst the
children which resulted in progressive loss of memory, communication issue and other issues.
Children with the Down syndrome usually have a delay in cognitive development along with the
severe deficits in the language production, short term memory and speech which further
increased the risk of developing depression and Alzheimer (Whitney et al., 2019). The mental
age of the children is also low and tend to exhibit low IQ compared to the children with the
Down syndrome. Due to speech and language deficit, young children of preschool often
subjected to discrimination, bully and stigma which frequently resulted in poor interpersonal
skills and social skills (Chu & Barlow, 2016). They often have low self-esteem, poor self-image,
anger management issues and low confidence compared to the children of the same age.
Capone, Brecher and Bay (2016), suggested that children with Down syndrome under 20 years

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often develop disruptive behaviours, hyper activeness, social exclusion and low self-confidence
from very young age compared to the normal children of their age. Over the years, with the
assistance of therapy and caregivers, they develop proper skills to connect with the society and
community. On the other hand children experience poor social relatedness, fatigued, mood-
related problems (frequent mood swings), day time sleepiness (Barisnikov & Straccia, 2019).
The children with Down syndrome are at high risk of developing chronic sleep difficulties and
eating difficulties. Since trisomy 21 influence genetic expression within the cell of the children,
soft tissue as well skeletal fluctuations lead to the blockage of their airways followed by sleep
apnoea. Therefore, children and adults with Down syndrome are at higher risk of experiencing
obstructive sleep apnoea compared to the normal population. Sertdemir and Akça (2018),
suggested that majority of the children with down syndrome fulfil the criteria of attention deficit
hyperactivity disorder and exhibit excessive compulsive as well as perfectionist behaviours
compared to normal children of the same age. Children with Down syndrome frequently display
repetitive behaviour such as unusual routines, rituals along with unusual stereotypy (Neil &
Jones, 2016). The researchers suggested that majority of the preschool or school going children
of 3 to 10-year-old children with Down syndrome displayed motoric repetitive behaviour such as
unusual finger mannerisms, unusual sensory interests and non-functional play. The restrictive
behaviours are also common amongst the children and due to the cognitive deficits associated
with trisomy 21, they are at high risk of developing obsessive-compulsive behaviours (Neil &
Jones, 2016). While these behaviours are common amongst the children, it is often a rare
instance where children with Down syndrome are more inclined to repeat self-injuries or harm.
In this context, psychological support from the caregivers or other psychotherapist can facilitate
the elimination of such behaviours. In Malaysia, Kiwanis Down Syndrome Foundation is one

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such non-profitable organization that offers support to the children with Down syndrome under 6
years old with a special education program for the children, training of the teacher to support the
children with special education need (Www.hati.my., 2020). Moreover, it also offers the
counselling to the family and children with Down syndrome for better management of the Down
syndrome. Apart from this organization, a range of non-profitable organizations in Malaysia that
offer development of gross motor skills, fine motor skills, speech therapy, self-help skills along
with formal physiotherapy. TAARANA is another organization in Malaysia that offer an
educational environment to children with cognitive and physical disabilities based on the
intensive intervention model. These educational opportunities not only address educational needs
but also enhances mental health and physical health needs.
Conclusion:
On a concluding note, Down syndrome is considered as a genetic disorder of infants
where trisomy of 21 observed that resulted in altering gene expression. Multiple critical genes
play a crucial role in Down syndrome where DSCR on 21q21.22 is accountable for various
clinical manifestation of down syndromes amongst the children. The common risk factors
include advanced maternal age, first born with Down syndrome, family history of Down
syndrome and being carriers of the genetic translocation for Down syndrome. The children with
Down syndrome experience poor motor function and speech and language problem which can be
reduced with a multidisciplinary approach to the care such as physical therapy, speech therapy.
The common phenotypic characteristics of the children with Down syndrome include a flattened
face, upward slating eye lids, poor muscle tone, broad and shorthand and short height. Apart
from these physical characteristics, the common complications observed for the disease include
leukemia, neurological disease, congenital heart diseases, difficulties in attention and analysis.

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On the other hand, the impact on psychological health include develops disruptive behaviours,
hyper activeness, social exclusion and low self-confidence. They often exhibit repetitive
behaviour such as unusual routines, rituals along with unusual stereotypy. Kiwanis Down
Syndrome Foundation is one such non-profitable organization that offers support to the children
with Down syndrome under 6 years old with special education program so that they can develop
skills for living a purposeful life.

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References:
Antonarakis, S. E. (2017). Down syndrome and the complexity of genome dosage
imbalance. Nature Reviews Genetics, 18(3), 147.
Antonarakis, S. E., Skotko, B. G., Rafii, M. S., Strydom, A., Pape, S. E., Bianchi, D. W., ... &
Reeves, R. H. (2020). Down syndrome. Nature Reviews Disease Primers, 6(1), 1-20.
Aversa, T., Crisafulli, G., Zirilli, G., De Luca, F., Gallizzi, R., & Valenzise, M. (2018).
Epidemiological and clinical aspects of autoimmune thyroid diseases in children with
Down’s syndrome. Italian journal of pediatrics, 44(1), 39.
Aversa, T., Valenzise, M., Corrias, A., Salerno, M., Iughetti, L., Tessaris, D., ... & Wasniewska,
M. (2016). In children with autoimmune thyroid diseases the association with Down
syndrome can modify the clustering of extra-thyroidal autoimmune disorders. Journal of
Pediatric Endocrinology and Metabolism, 29(9), 1041-1046.
Barisnikov, K., & Straccia, C. (2019). Social adaptive skills and psychopathology in adults with
intellectual disabilities of non-specific origin and those with Down syndrome. Research
in developmental disabilities, 87, 31-42.
Boutot, E. A., & DiGangi, S. A. (2018). Effects of Activation of Preferred Stimulus on Tummy
Time Behavior of an Infant with Down Syndrome and Associated Hypotonia. Behavior
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Capone, G. T., Brecher, L., & Bay, M. (2016). Guanfacine use in children with down syndrome
and comorbid attention-deficit hyperactivity disorder (ADHD) with disruptive
behaviors. Journal of child neurology, 31(8), 957-964.

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Carozza, S. E., Bae, H., Meath, T., Branscum, A., Bovbjerg, M. L., & Langlois, P. H. (2017).
Evaluation of maternal health and labor and delivery conditions as risk factors for
childhood leukemias in children with Down syndrome. Cancer epidemiology, 46, 36-41.
Chu, S. Y., & Barlow, S. M. (2016). A call for biomechanics to understand hypotonia and speech
movement disorders in Down syndrome. Advances in Communication Disorder, 2-40.
Head, E., T Lott, I., M Wilcock, D., & A Lemere, C. (2016). Aging in Down syndrome and the
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Postolache, L. (2019). Abnormalities of the optic nerve in Down syndrome and associations with
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