Down Syndrome - Clinical Case Review (Group 3)

Case:
This is a case of R.D., a 5 y/o male, born at full-term of gestation (40 weeks) on
September 1, 2016 to a 30 y/o [11(1001)] mother via normal delivery with cephalic
presentation. Pt.'s mother sought for medical help after the pt. presented with delayed
milestones starting at 8 mos. old. Pt. underwent a series of tests like Karyotype,
Chromosomal Analysis, and Genetic testing which showed probable Down Syndrome. It
is not until the pt. was 2 y/o when the pt. became medically diagnosed with Down
Syndrome. Pt. has (+) Brushfield Spots on (B) eyes, (+) umbilical hernia, and (+) sandal
gap deformity on (B) LE. Pt.'s mother is also c/o of mild hypotonia on (B) UE / LE. Pt.'s
mother goal was for the pt. to achieve near normal function and independence, as well
as to prevent the development of possible complications and improve the capability of
the pt. to interact and communicate. The pt. was then referred to Pediatric Rehabilitation
for further evaluation and treatment.

Title/Diagnosis: Down Syndrome (Trisomy 21)

Differential Diagnosis:
● Lesch-Nyhan syndrome (Rosso et al., 2020)
● Edward Syndrome/Trisomy 18 (Carey, 2021)
● Trisomy 13 (Carey, 2021)

Description:
Down Syndrome (DS) is one of the most common chromosomal disorders
for pediatric patients which affects 1 out of 800 births worldwide (Bull, 2020). DS
was first described by John Langdon Down in 1866, which involves the
affectation of multiple bodily systems i.e. musculoskeletal, neurological, and
cardiovascular (Antonarakis et al., 2020).
According to Coppedè (2016) DS has three possible causes, first is the
trisomy of chromosome 21 which is caused by ‘meiotic nondisjunction’ and
accounts for 90-95% of DS cases. The said event causes a gamete to have two
copies of chromosome 21 due to its failure to separate, which then forms three
copies of chromosome 21 once the gamete which contains two copies of the said
chromosome, unites with another gamete having a normal, single copy of
chromosome 21. The second cause is mosaicism which accounts for 2-4% of the
cases. In mosaic DS, some of the cells have a normal number of chromosome
21, and some cells have three copies or trisomy of the said chromosome, this
occurs due to a mitotic error following fertilization. The last known possible cause
for DS is the Robertsonian translocation which accounts for the remaining cases
of DS. In this event, chromosomal rearrangements or translocation of the long
arm of chromosome 21 occurs, resulting in partial trisomy for the said
chromosome. Kazemi, Salehi, & Kheirollahi (2016) expounded that the
translocated segment of chromosome 21 usually attaches to chromosome 14 or
15 and can be inherited. Once the inherited chromosome with an additional copy
of chromosome 21 combines with a normal chromosome with a normal two
copies of chromosome 21, DS will probably take place.
There are multiple prenatal screening procedures for early detection of
DS. Combined test of ultrasound measuring nuchal translucency and measure of
maternal serum beta-hCG with pregnancy-associated plasma protein A are
performed during 11-15 weeks of gestation (MacLennan, 2019). MacLennan
(2019) added that an increase on nuchal translucency is highly associated with
DS. On the other hand, Bull (2020) stated that noninvasive prenatal screening
procedures such as cell-free DNA (cfDNA) reduces the use of invasive screening
procedures and has a high specificity for detection of DS (99.7%).
Aside from the causes of DS, the study of Coppedè (2016) focuses more
on identifying the risk factors associated with the development of DS such as the
maternal age which indicates that the possibility of giving birth to a child with DS
increases with age. Other risk factors include recombination errors, genomic
instability in mothers of DS individuals, and folate metabolism and maternal risk
of birth of a child with DS (Coppedè, 2016). Yang (as cited in Coppedè, 2016)
identified additional risk factors associated with the maternal lifestyle as well as
environmental factors such as smoking, increased weight during pregnancy, use
of contraceptive pills, and radiation exposure.

Causes:
- Failure of chromosome 21 to segregate normally results in having a triple
copy of it. This is the most common type of down syndrome (Kazemi et al.,
2016).
- Translocation of chromosome 21 happens when a part of this
chromosome is transferred to another chromosome. The most common
chromosomes that get be transferred with parts of chromosome 21 are
chromosome 14 and 15 (Kazemi et al., 2016)

Other causes:
- Isochromosome (ring chromosome) - a condition in which two long arms
of chromosome separate together rather than the long and short arm
separating together during egg sperm development (Huijsdens-van
Amsterdam et al., 2018)
Risk factors:
Non-modifiable
● Prenatal
1. Maternal age
Increased maternal age of conception can challenge healthy oocyte
maturation and chromosome segregation (Pal et al., 2021).

2. Gene carriers
Mother being the carrier of the gene defect could lead to higher
chances of having a child with down syndrome than if the father is the
carrier. Chances are still high if either of the parents are carriers (Kazemi
et al., 2016).

3. History of having a first child with down syndrome

Chances are higher that succeeding children could also be affected
by the of down syndrome if parents are a carrier of the affected gene
(Kazemi et al., 2016).

4. Consanguinity
People married to their relatives showed increased chances of
producing an offspring with down syndrome (Shalaby, 2011).

● Perinatal
1. Environment
Exposure to anything unwanted in the surroundings can lead to
miscarriage or development of birth disorders (Coppedè, 2016).

● Postnatal
1. Weight at birth
Infants with down syndrome showed decreased birth weight
compared to those without the condition (Sparks et al., 2016).

2. APGAR
Babies with down syndrome have lower apgar score at birth
(Sparks et al., 2016).

3. Preterm
 Infants diagnosed with down syndrome are more likely to be
preterm at birth (Brock et al., 2021).

Modifiable
● Prenatal

1. Maternal occupation
Occupation of mothers with exposure to toxic agents has higher
chances of having children with chromosomal abnormalities (Antonarakis
et al., 2020).

2. Paternal occupation
Environmental exposure to pyrethroid insecticides was linked to an
increased rate of aneuploidy in spermatozoa, including chromosome 21
disomy and occupational factors existing in a contemporary work setting
such as exposure to mechanical vibrations or sitting for more than six
hours at work increased sex chromosomes disomy (Radwan et al. 2015).
Additionally, according to Jurewicz et al. (2015), exposure to specific air
pollutants (PM2.5) was linked to increased disomy of chromosome 21 and
sex chromosomes.

3. Vegetarian mother
Pregnant vegetarian mother that undertook an alpha fetoprotein
test showed false positive results for screening down syndrome (Pistollato
et al., 2015).

4. Paternal diet
Those who engage in having a healthier diet than processed foods
are less likely to have sperm with chromosome 21 defect (Coppedè,
2016).
Men with high folate intake had lower frequencies of spermwith
disomies X and 21, sex nullisomy and a lower aggregate measure of sperm aneuploidy
compared with men with lower intake (Young et al. 2008).

● Perinatal
1. Smoking
Smoking can cause errors that could happen in cell division during
pregnancy (Ghosh & Kumar, 2013).

2. Use of oral contraceptive

 Contraceptive results in disrupting the healthy environment in the
ovary. It causes toxins that lead to decrease of blood supply that later on
can affect cell division (Ghosh & Kumar, 2013).

3. Folate intake
Pregnant mothers who are likely to intake 6 mg of folic acid
supplement daily are used to prevent occurrence of down syndrome
(Cristina et al., 2011).

● Postnatal

1. Smoking
Maternal smoking has been found to be associated with risk of developing
CHD in DS infants (Alverson et al., 2011; Bergstrom et al., 2016).

EXAMINATION

Subjective:
1. Past medical history
a. Do you have any underlying conditions? Does your family have a
history of Down Syndrome?
- The reported event of increased maternal total cholesterol or
hypercholesterolemia is associated with normal response of
the mother during pregnancy and is considered to be an
adaptive response to satisfy the high cholesterol demand of
the growing fetus (Sobrevia, 2013, p.104).
- During pregnancy, the blood pressure of the mother was
indicated as borderline (120/80mmHg) wherein gestational
hypertension and preeclampsia suggests a late-onset type of
fetal growth restriction which is a major contributor to the
causal pathway of DS pregnancies and perinatal mortality
(Yao et al., 2018).

2. Onset of symptoms
a. What manifestations did you notice in your child?
- The mother of the child presented with pictures of her child
wherein the skin of the patient is fair and his eyes were
 bluish-white and was obese but later resolved though diet.
Most DS patients demonstrate many musculoskeletal deficits
such as hypotonia, ligamentous laxity, poor balance, and a
lack of postural control that cause difficulties in adapting to
gravity and the surrounding environment (Tecklin, 2015, p.
391-392). Obesity may be caused by hyperthyroidism and
hypotonia which can lead to cardiovascular disease, stroke,
hypertension and diabetes in adulthood of the child. This
might also cause obstructive sleep apnea and can be
managed through proper diet and regular exercise during
childhood (Diamandopoulos & Green, 2018).

3. Pathophysiology
a. Do you have any family members who have the same condition of
Down syndrome?
- According to Perkins (2017), DS is known as a complex
genetic disorder of chromosome 21 which occurs during
meiotic cellular division phase. Human development begins
with the fertilisation of an ovum (female gamete) by a
spermatozoon (male gamete). When a spermatozoon comes
into contact with the ovum, the zona pellucida and the
plasma membrane fuse, preventing entry by other sperm
(Kenner and Lott, 2014). During fertilisation, meiotic cell
division occurs where the male and the female pronucleus
fuse. This results in two haploid numbers of chromosomes
(22 autosomes and 1 sex chromosome) from each gamete
cell. The zygote is formed and contains the diploid number of
chromosomes necessary to create a unique human being.
Genetic disorders can influence the course of the foetal
development and pregnancy and have implications for both
the mother and the baby. All human cells, except for the
gamete cells (ovum and sperm), normally contain 46
chromosomes (diploid number) consisting of 1 pair of sex
chromosomes and 22 pairs of autosomes. Chromosomes
are made up of genes that determine how the foetus forms
in utero and how the baby grows after birth. They also
influence physical characteristics, such as eye and hair
colour, and the probability of developing a disease in the
future.
4. Medications
a. Did you take any medications during your pregnancy?
- The mother of the child said that she consumed folic acid
and Vitamin B1 and B2 during her pregnancy which are
prescribed by her doctor. It has been found to be associated
in DS patients because lack of folic acid supplements during
pregnancy could result in CHD in newborns with DS
(Brandalize et al. 2009; Locke et al. 2010; Bean et al. 2011).
Epidemiological studies have shown that a significant
number of women who took folic acid supplements during
pregnancy exceeded the Institute of Medicine's
recommended tolerable upper limit of 1,000 μg/day. In
addition, studies also reported consumption of 400 μg/day of
natural food folate plus FA-containing prenatal supplements
resulted in supra-nutritional folate status with the greatest
increases in pregnant women followed by lactating and
non-pregnant women (Barua et al., 2014).

5. Tests Conducted
a. Have you and the baby undergone any clinical examinations
before, during, after giving birth?
- Amniocentesis or chorionic villus sampling is an invasive
prenatal screening which has a 99% accuracy in determining
diagnosis of down syndrome during pregnancy (Bull, 2020).
The positive predictive value (PPV) of serum screening is
poor. First-trimester serum screening using nuchal
translucency measurement and serum markers
(pregnancy-associated plasma protein A [PAPP-A] and free
beta human chorionic gonadotropin [hCG]) has a 2–3% PPV,
while second trimester screening using either a triple or quad
screen (alpha-fetoprotein [AFP], estriol, beta-hCG with
inhibin for quad screen) has a 2% PPV. Combined first- and
second trimester screening (referred to as contingent
screening, sequential screening or integrated screening,
each with slight differences in testing protocol), all have
slightly improved Down syndrome detection rates but still
have only 4% PPV. Recognition of cell free fetal DNA in
maternal circulation, in combination with improved genetic
sequencing technology, would prove to be the key elements
 that catalyzed a major advance in prenatal aneuploidy
screening (Gray & Wilkins-Haug, 2018).
- Cell-free prenatal screening and parallel sequencing of
maternal plasma cell-free DNA is a non-invasive prenatal
screening that can detect Down syndrome at pregnancy with
an accuracy of 99.7% (Bull, 2020). Cell-free nucleic acids
are associated with inflammatory diseases (i.e. lupus,
glomerulonephritis, pancreatitis), rapid cell turnover (as seen
in cancer), and tissue injury (as seen in trauma, stroke and
myocardial infarct) and are thought to originate primarily
from maternal hematopoietic cells. This became relevant to
pregnancy when it was reported that there is fetal DNA in
maternal plasma and serum, as evidenced by the presence
of fetal derived Y sequences in maternal blood. Fetal
cell-free DNA can be detected as early as 5–7 weeks of
gestation and is rapidly cleared from the maternal circulation
within hours. The half-life of fetal cfDNA is about 1 h in
healthy women, and almost all fetal cfDNA is eliminated
within 48 h of delivery. The fetal fraction is known to be
altered by gestational age, maternal body mass index (BMI)
and aneuploidy, while it is unaffected by several other clinical
and demographic variables (Volik et al., 2016; Canick et al.,
2013; Yu et al., 2013; Pegament et al., 2014).

Objective:
1. Blood Pressure
- Young individuals with Down Syndrome tend to have lower blood
pressure (Santoro et al., 2020). Individuals with Down syndrome
should have an annual examination of the heart (Antonarakis et al.,
2020).

2. Pulse Rate
- DS was found to have a strong association with heart malformation
which arises from abnormal development of endocardial cushions
during resulting in CHD (Plaiasu, 2017).

3. Respiratory Rate
- The patient does not present any respiratory problems but studies
showed that patients with DS usually presents with poor respiratory
 symptoms including stridor, wheezing and noisy breathing which
can contribute to the possibility of airway anomalies (Ivan and
Crowell, 2014).

4. Cognitive Examination
- Children with down syndrome show impairment in cognitive aspects
which can be due to the early exposure to brain operations (Kim et
al., 2017).

5. Ocular Inspection & Palpation

- Check if the child presents with epicanthal folds, flat nasal bridge,
short neck, small ears, brushfield spots, single palmar crease and a
small mouth with a large protruding tongue which are common
physiogenic features of DS patients that are often accompanied by
muscular hypotonia (Roizen and Patterson 2003; Weijerman and
de Winter 2010; Bull, 2020).
- DS patients may also have small, brachycephalic (flat)
head,excessive skin on the nape of the neck, short fifth finger with
clinodactyly (i.e., a bent or curved finger due to mid phalanx
hypoplasia) which are considered common physical findings in this
condition (Ivan & Crowell, 2014).
- Dentition is often delayed with DS patients and may be spotty
(Tecklin, 2015, p.392).
- The abdomen may be slightly protuberant secondary to hypotonia,
and the chest may take on an abnormal shape secondary to
congenital heart defect (Tecklin, 2015, p.392).
- Umbilical hernia is a predisposing factor in children with down
syndrome. It requires prompt surgical intervention to prevent risks
such as viscous strangulation. The parents and caregiver should be
well informed about the condition. Asymptomatic cases should be
monitored very closely with their primary care provider (Kepertis et
al., 2020).
- Simian crease: A single crease is observed across the palm on one
or both hands in the majority of children with DS (Tecklin, 2015,
p.392).
- Sandal gap: A wide gap between the first and the second toes, with
a crease running between them on the sole of the foot is commonly
found in children with DS (Roizen and Patterson 2003; Weijerman
and de Winter 2010).
6. Range of Motion
- Muscle variations may also be present, including an absent
palmaris longus and supernumerary forearm flexors. There is also
a lack of differentiation of distinct muscle bellies for zygomaticus
major and minor and the levator labii superioris, which may account
for the typical facial appearance of the child with Down Syndrome
(Tecklin, 2015, p.392).
- Down syndrome (DS) musculoskeletal problems are widespread
but underreported. The combination of ligamentous laxity and low
muscle tone increases the risk of a variety of musculoskeletal
problems as well as a delay in motor milestone learning. (Foley, C.,
& Killeen, O. G. (2018).
- Patella instability has been documented in DS to range from minor
subluxation to total dislocation. Patella instability can cause a
change in gait as well as a reduction in knee range of motion.
(Foley, C., & Killeen, O. G. (2018).

7. Manual Muscle Test

- People with Down syndrome (DS) usually display reduced physical
fitness (aerobic capacity, muscle strength and abnormal body
composition), motor proficiency impairments (balance and postural
control) and physical functional limitations. (Silva, V. et al (2017)
- Dupre & Weidman-Evans (2017) noted that Patients also have
less-than-normal muscle strength in their hands and lower
extremities. The resulting deficits in muscle strength and tone
severely affect the achievement of developmental milestones such
as independent walking in younger patients and the activities of
daily living in older patients

8. Functional Muscle Testing

- Consequently, they experience changes in dynamic balance,
postural control and other motor proficiency domains, as they are
slower to adapt to motor task demands and environmental changes
and have less ability to perform anticipatory postural adjustments.
These changes also impair visual motor integration, agility, muscle
strength, motor control and movement reaction time. (Silva, V. et al
(2017)
- Assessing grip strength and manual dexterity in patients with Down
syndrome is important because patients usually have decreased
manual motor control (Dupre & Weidman-Evans (2017)
9. Tone Assessment
- In addition to cognitive and developmental concerns, an oft-cited
issue with individuals with Down syndrome is hypotonia, or low
muscle tone (Skotko & Tenenbaum, 2016)
- Hypotonia is a well-described feature of DS, has significant and
widespread functional impact, and contributes to increased risk of a
number of musculoskeletal disorders, a delay in acquisition of
motor milestones and lower levels of physical activity in children
with DS. (Foley, C., & Killeen, O. G. (2018)
- Youths with Down syndrome tend to exhibit a reduced postural tone
(hypotonia) that negatively affects muscular coactivation and
balance reactions, and relates to deficits in proprioceptive feedback
and to hypermobility or joint laxity (Maïano et al (2019)

10. Gait Assessment

- Down Syndrome (DS) produces a distinct gait phenotype
characterized by low walking speed, reduced step length, increased
step width, balance deficits, joints instability and kinematic
alterations such as excessive pelvic tilt and knee flexion, external
rotation of hip, tibia and foot, limited hip and knee range of motion.
(Zago, M. et al. (2019)

11. Balance
- According to Maïano et al (2019) the postural balance deficit
displayed by youths with Down syndrome could be explained by
disturbances in the regulation system of balance or postural control.
- Children with DS are more likely to lose their balance when coming
across obstacles in their surroundings (Alsakhawi & Elshafey
(2019)

12. Coordination
- According to Azzam (2019), children with down syndrome have a
delay in gross motor coordination due to different factors such as
hypotonic abdominal muscles, joint laxity and muscle weakness
especially trunk and lower extremity muscles. These factors greatly
affect the skill development in pediatric DS.

13. Pulmonary Assessment

 - According to Colvin & Yeager, (2017) pediatric population with
down syndrome have respiratory diseases. Affecting both their
upper and lower airways, that greatly increases their mortality rate.
- DS through many mechanisms, including increased hemodynamic
stress in those with congenital heart disease, hypoxemia through
impaired ventilation to perfusion matching secondary to
developmental lung abnormalities, pulmonary hypoplasia from
pulmonary vascular endothelial dysfunction, and an increase in
pulmonary vascular resistance often related to pulmonary
comorbidities. (Bush, D., Galambos, C., & Dunbar Ivy, D. (2020).
- Pulmonary function and chest expansion tests have potential to be
an initial indicator of pulmonary problems in people with Down
syndrome at a young age. (Laibsirinon et al (2014)
- Laibsirinon et al (2014) also stated that chest expansion of boys
with Down syndrome was significantly smaller than healthy boys.
Chest expansion or mobility of chest wall is affected by normal
function of respiratory muscles, and mobility of costovertebral joints
as well as compliance of lungs.
- Auscultation may reveal a pronounced pulmonary component of the
second heart sound, diastolic murmur in second left intercostal
space, and moderate holosystolic heart murmur that radiates to
axilla. (Salamanca & Savaleta (2021)

14. Cardiac Assessment

- Down syndrome is associated with congenital heart defects, hence
it is important to monitor their heart very closely to prevent serious
complications (Nanjundaswamy. 2015)
- On auscultation of a DS patient with Complex cyanotic heart
disease a holosystolic type murmur 3/6 on the 3rd left parasternal
border would be audible. (Siama et al (2020)

15. Feeding Assessment

- Nevertheless, given that one of the features of DS is a high
prevalence of obesity, as well as the controversy regarding lower
resting energy expenditure as a contributor to this feature,
monitoring and emphasizing a healthy diet and lifestyle for
preventing obesity is recommended. (Magenis et al (2017)

Diagnostic Test:
1. Amniocentesis
 - Amniocentesis is the most common prenatal diagnostic test for
down syndrome but the most cell-free fetal DNA test is the most
preferable (Kazemi et al., 2016).
2. Ultrasound (Soft Markers)
- Identifying sonographic soft markers during ultrasound such as
increased nuchal translucency thickness, and hypoplasia of the
nasal bone, has high sensitivity for diagnosis of Trisomy 18
(Cereda, & Carey, 2012).
3. Chorionic Villi Sampling
- The use of cytogenetic evaluation with chorionic villi sampling helps
distinguish trisomy 13 or Patau syndrome from other similar
chromosomal disorders because the use of sonographic tests may
yield overlapping results with Edward syndrome and Down
syndrome (Williams, & Brady, 2021).
Functional Testing:
1. Timed Up and Go (TUG) Test
- According to Martin, K., Natarus, Martin, J., & Henderson (2017),
Timed Up and Go (TUG) test was found to be a clinically valid
outcome measure for dynamic balance assessment for children
and adolescents with DS, and has an MDC of 1.26 seconds and
high test-retest reliability in the said population (TUG ICC 2,k;
r=0.923).

Desired Outcomes:
1. Limit development of other complications
2. Manage and improve the present complications
3. Increase Quality of life
4. Improve in functional independence

Outcome Measures
● Quality of Life Inventory-Disability (QI-Disability) measure
QI-Disability is an outcome measure that focuses on determining
the quality of life of pediatric up to adolescent patients which are
intellectually challenged. This questionnaire is specifically made for
individuals with a condition of Down Syndrome, Rett Syndrome, and
Cerebral Palsy. It is composed of 32 questions that must be answered by
the primary caregiver of the patient.
QI-Disability item scores were scored as follows, ‘Never’ was
scored as 0, ‘Rarely’ was scored as 25, ‘Sometimes’ as 50, ‘Often’ as 75,
and ‘Very Often’ as 100. The total scores for each domain was then
 divided by the number of items of the specific domain, then the sum of
domain scores was then divided by the number of domains to get the total
score. Cronbach’s alpha values for QI-Disability ranged from 0.72 for
“physical health” to 0.90 for “positive emotions” and composite reliability
values ranged from 0.75 for “physical health” to 0.91 for “positive
emotions”, each > 0.7 and indicative of satisfactory convergent validity
(Downs et al., 2018).

● Pediatric Evaluation of Disability Inventory Computer AdaptiveTest

(PEDI-CAT)
PEDI-CAT is an outcome measure that measures three
domains which include daily activity, mobility, social or cognitive, and
mobility. It is made specifically for children with physical or behavioral
disabilities. This is an online tool that is answered by the primary
caregiver. Total score is computed automatically online. Normal score
range is 30-70, this is interpreted that the functional ability of the patient is
normal for their age. A score less than 30 would be interpreted as having
a decreased functional ability in relation to what is expected on that
patient's age.
PEDI-CAT showed reliability of ICC > 0.86. Test-retest
reliability scored ICC = 0.96–0.99 for all its domains. Concurrent validity
had a score of 0.32 to 0.83 (Cordeiro et al., 2020). MDC values were as
follows: Mobility = 0.93, Daily Activities = 0.75, Social/Cognitive = 1.58
(Fragala-Pinkham et al., 2015).
● Movement Assessment Battery for Children–Second Edition
(MABC-2)

MABC-2 The MABC-2 Test is designed to identify and

describe impairments in motor performance of children and adolescents
from 3 to 16 years of age divided into three age bands (3–6y, 7–10y,
11–16y). The test is composed of two parts: the Performance Test and the
Checklist. Only the Performance Test was used in the current study; it
involves children completing a series of eight fine and gross motor tasks
grouped into three subscales: Manual Dexterity, Aiming and Catching, and
Balance. The MABC-2 Test yields several scores: raw score and standard
score on the individual test items, subscale standard score with equivalent
centiles, and a total standard score and centile equivalent. The total
impairment score is translated to age-related centile norms with the fifth
centile as the cut-off point to indicate children with movement difficulties.
Standard scores have a mean of 10 and an SD of 3. The total score is
 interpreted based on the percentile cut-offs: <5 th percentile = significant,
motor difficulty 6 – 15th percentile = careful monitoring suggested, >15th
percentile = no significant motor difficulty.

Internal consistency for the MABC-2 Test was α = 0.90.

Test–retest reliability for the total score was excellent, with an intraclass
correlation coefficient of 0.97. A small to medium magnitude of treatment
effect was captured by the MABC-2 Test. The minimal detectable change
(MDC) was 0.28 points whereas the minimal important difference (MID)
values were from 2.36 to 2.50. All subscales except balance showed
acceptable validity in differentiating groups of children whose physical
performance had improved or remained stable (Wuang et al., 2012).

ASSESSMENT
Overall Contraindications/Precautions
1. Monitor the patient’s weight and follow the weight-for-height in standard
growth charts of the National Center for Health Statistics or the World
Health Organization.
2. Review the risk of hearing loss associated with serous otitis media.
3. Check the child’s vision, and use developmentally appropriate subjective
and objective criteria at each well-child visit.
4. The presence of torticollis or neck stiffness should alert one about the
possibility of AAI and subsequent spinal cord compression.
5. Wheezing and stridor are suggestive of upper and/ or lower airways
abnormalities such as laryngomalacia, tracheomalacia, airway
compression from large vessels, tracheal bronchus, bronchomalacia,
tracheoesophageal fistula, or severe GERD.
6. Cyanosis, heart murmurs, and tachycardia are supportive findings for
complex cardiac malformations (e.g., atrioventricular canal, ventricular
septal defects, atrial septal defects, patent ductus arteriosus, tetralogy of
Fallot, hypoplastic left heart syndrome, and pulmonary hypertension).
7. Assess genitalia for micropenis, cryptorchidism, and hypospadias (in
boys) or lower labial index (a labia majora that is shorter and wider than
normal in girls).
8. Perform a careful neurologic examination, paying attention to the tone of
lower/upper extremities; hypertonia and/or weakness suggest AAI and
subsequent spinal cord compression.
PROGNOSIS

58 years old is the median age of life expectancy for individuals with down
syndrome (MacLennan, 2020). Despite this life expectancy, individuals with down
syndrome may have poor prognosis because of the numerous comorbidities this
condition can develop. Among the comorbidities that accompany it is coronary heart
disease, leukemia, and Alzheimer's disease (Santoro et al., 2020). If not properly
managed, it can cause further problems for individuals with this condition.

References:

Antonarakis, S. E., Skotko, B. G., Rafii, M. S., Strydom, A., Pape, S. E., Bianchi,
D. W., Sherman, S. L., & Reeves, R. H. (2020). Down syndrome. Nature
Reviews Disease Primers, 6(1), 9. Retrieved on Sep 21, 2021 from
https://doi.org/10.1038/s41572-019-0143-7

Azzam, A. M. (2019). Efficacy of Sensory Integration Therapy in Improving Gross

Motor Coordination and Grip Control in Down Syndrome Children. World
Journal of Neuroscience, 09(02), 23–38.
https://doi.org/10.4236/wjns.2019.92002

Bull, M. J. (2020). Down Syndrome. New England Journal of Medicine, 382(24),

2344–2352. Retrieved on Sep 21, 2021 from
https://doi.org/10.1056/NEJMra1706537

Colvin, K. L., & Yeager, M. E. (2017). What people with Down Syndrome can

teach us about cardiopulmonary disease. European Respiratory Review,

26(143), 160098. Retrieved on September 21, 2021 from:
https://doi.org/10.1183/16000617.0098-2016

Foley, C., & Killeen, O. G. (2019). Musculoskeletal anomalies in children with

 Down syndrome: An observational study. Archives of Disease in
Childhood, 104(5), 482–487. Retrieved on Sep 21, 2021 from
https://doi.org/10.1136/archdischild-2018-315751

Huijsdens-van Amsterdam, K., Page-Christiaens, L., Flowers, N., Bonifacio, M.

D., Ellis, K. M. B., Vogel, I., Vestergaard, E. M., Miguelez, J., de Carvalho,
M. H. B., Sistermans, E. A., & Pertile, M. D. (2018). Isochromosome 21q is
overrepresented among false-negative cell-free DNA prenatal screening
results involving Down syndrome. European Journal of Human Genetics,
26(10), 1490–1496. Retrieved on September 21, 2021 from:
https://doi.org/10.1038/s41431-018-0188-1

Ikbal Atli, E. (2021). What Causes Down Syndrome? In Genetics and Etiology of
Down Syndrome [Working Title]. IntechOpen. Retrieved on Sep 21, 2021
from https://doi.org/10.5772/intechopen.96685

Kazemi, M., Salehi, M., & Kheirollahi, M. (2016). Down Syndrome: Current
Status, Challenges and Future Perspectives. International Journal of
Molecular and Cellular Medicine, 5(3), 125–133.

Kepertis, C., Tsopozidi, M., Anastasiadis, K., Godosis, D., Demiri, C., &
Spyridakis, I. (2020). Incarcerated Umbilical Hernia in a 14-Month-Old
Female: A Rare Case of Bowel Strangulation. Pediatric Reports, 12(3),
68–71. Retrieved on September 22, 2021 from:
https://doi.org/10.3390/pediatric12030017

Kim, G. E., Sin, D. S., Kim, S. S., Lee, C.-H., Cho, N.-J., & Lee, E. Y. (2019).
End-stage renal disease in a Down syndrome patient caused by delayed
diagnosis of non neurogenic bladder: A case report. Medicine, 98(15),
e15145. Retrieved on Sep 22, 2021 from
https://doi.org/10.1097/MD.0000000000015145

Kim, H. I., Kim, S. W., Kim, J., Jeon, H. R., & Jung, D. W. (2017). Motor and
Cognitive Developmental Profiles in Children With Down Syndrome.
Annals of Rehabilitation Medicine, 41(1), 97. Retrieved on Sep 22, 2021
from https://doi.org/10.5535/arm.2017.41.1.97

Lagan, N., Huggard, D., Mc Grane, F., Leahy, T. R., Franklin, O., Roche, E.,
 Webb, D., O’ Marcaigh, A., Cox, D., El-Khuffash, A., Greally, P., Balfe, J.,
& Molloy, E. J. (2020). Multiorgan involvement and management in
children with Down syndrome. Acta Paediatrica, 109(6), 1096–1111.
Retrieved on Sep 23, 2021 from https://doi.org/10.1111/apa.15153

MacLennan, S. (2020). Down’s syndrome. InnovAiT: Education and Inspiration

for General Practice, 13(1), 47–52. Retrieved on Sep 23, 2021 from
https://doi.org/10.1177/1755738019886612

Nanjundaswamy, N. H. (2015). Anaesthesia for a Rare Case of Down’s

Syndrome with Morgagni’s Hernia Undergoing Laparoscopic Repair.
JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. Retrieved on
September 22, 2021 from https://doi.org/10.7860/JCDR/2015/13199.5869

Pal, U., Halder, P., Ray, A., Sarkar, S., Datta, S., Ghosh, P., & Ghosh, S. (2021).
The etiology of Down syndrome: Maternal MCM9 polymorphisms increase
risk of reduced recombination and nondisjunction of chromosome 21
during meiosis I within the oocyte. PLOS Genetics, 17(3), e1009462.
Retrieved on Sep 23, 2021 from
https://doi.org/10.1371/journal.pgen.1009462

Rosso, M., Fremion, E., Santoro, S. L., Oreskovic, N. M., Chitnis, T., Skotko, B.
G., & Santoro, J. D. (2020). Down Syndrome Disintegrative Disorder: A
Clinical Regression Syndrome of Increasing Importance. Pediatrics,
145(6), e20192939. Retrieved on Sep 23, 2021 from
https://doi.org/10.1542/peds.2019-2939

Wuang, Y.-P., Su, J.-H., & Su, C.-Y. (2012). Reliability and responsiveness of the
Movement Assessment Battery for Children-Second Edition Test in
children with developmental coordination disorder: Reliability and
Responsiveness of the MABC-2 Test. Developmental Medicine & Child
Neurology, 54(2), 160–165.
https://doi.org/10.1111/j.1469-8749.2011.04177.x

Carey, J. C. (2021). Trisomy 18 and trisomy 13 syndromes. Cassidy and

Allanson's Management of Genetic Syndromes, 937-956. Retrieved on
Sep 23, 2021 from https://doi.org/10.1002/9781119432692.ch58

Santoro, J. D., Lee, S., Mlynash, M., Mayne, E. W., Rafii, M. S., & Skotko, B. G.
(2020). Diminished Blood Pressure Profiles in Children With Down
 Syndrome. Hypertension, 75(3), 819–825. Retrieved on Sep 23, 2021 from
https://doi.org/10.1161/HYPERTENSIONAHA.119.14416

Santoro, J. D., Pagarkar, D., Chu, D. T., Rosso, M., Paulsen, K. C., Levitt, P., &

Rafii, M. S. (2020). Neurologic complications of Down syndrome: A

systematic review. Journal of Neurology. Retrieved on Sep 23, 2021 from
https://doi.org/10.1007/s00415-020-10179-w

Yao, R., Contag, S. A., Goetzinger, K. R., Crimmins, S. D., Kopelman, J. N.,

Turan, S., & Turan, O. M. (2020). The role of fetal growth restriction in the
association between Down syndrome and perinatal mortality. The Journal
of Maternal-Fetal & Neonatal Medicine, 33(6), 952-960. Retrieved on
Sep 23, 2021 from https://doi.org/10.1080/14767058.2018.1511695

Ivan, D. L., & Cromwell, P. (2014). Clinical practice guidelines for management of

children with Down syndrome: Part I. Journal of Pediatric Health Care,

28(1), 105-110. Retrieved on Sep 23, 2021 from
https://doi.org/10.1016/j.pedhc.2013.05.002

Coppedè, F. (2016). Risk factors for Down syndrome. Archives of toxicology,

90(12), 2917-2929. Retrieved on Sep 23, 2021 from

https://doi.org/10.1007/s00204-016-1843-3

Diamandopoulos, K., & Green, J. (2018). Down syndrome: An integrative review.

Journal of neonatal nursing, 24(5), 235-241. Retrieved on Sep 23, 2021

from https://doi.org/10.1016/j.jnn.2018.01.001

Cordeiro, L., Villagomez, A., Swain, D., Deklotz, S., & Tartaglia, N. (2020).

Adaptive Skills in FXS: A Review of the Literature and Evaluation of the

PEDI-Computer Adaptive Test (PEDI-CAT) to Measure Adaptive Skills.
 Brain Sciences, 10(6), 351. Retrieved on Sep 23, 2021 from
https://doi.org/10.3390/brainsci10060351

Downs, J., Jacoby, P., Leonard, H., Epstein, A., Murphy, N., Davis, E., …
Williams, K. (2018). Psychometric properties of the Quality of Life
Inventory-Disability (QI-Disability) measure. Quality of Life Research.
Retrieved on Sep 23, 2021 from https://doi:10.1007/s11136-018-2057-3

Martin, K., Natarus, M., Martin, J., & Henderson, S. (2017). Minimal Detectable
Change for TUG and TUDS Tests for Children With Down Syndrome.
Pediatric physical therapy : the official publication of the Section on
Pediatrics of the American Physical Therapy Association, 29(1), 77–82.
Retrieved on Sep 23, 2021 from
https://doi.org/10.1097/PEP.0000000000000333

Brock, J.-A. K., Walsh, J. D., & Allen, V. M. (2021). The Effect of Fetal Trisomy 21
on Adverse Perinatal Obstetrical Outcomes in Nova Scotia, 2000–2019.
Journal of Obstetrics and Gynaecology Canada, 43(5), 583–588.
https://doi.org/10.1016/j.jogc.2020.09.019

Coppedè, F. (2016). Risk factors for Down syndrome. Archives of Toxicology,

90(12), 2917–2929. https://doi.org/10.1007/s00204-016-1843-3

Cristina, E., Lancia, B., Matos, J., & Goloni Bertollo, E. M. (2011). Abnormal
Folate Metabolism and Maternal Risk for Down Syndrome. In A. Day
(Ed.), Genetics and Etiology of Down Syndrome. InTech.
https://doi.org/10.5772/19373

Ghosh, S., & Kumar, S. (2013). Risk Factors for Down Syndrome Birth:
Understanding the Causes from Genetics and Epidemiology. In S. Dey
(Ed.), Down Syndrome. InTech. https://doi.org/10.5772/52903

Kazemi, M., Salehi, M., & Kheirollahi, M. (2016). Down Syndrome: Current
Status, Challenges and Future Perspectives. International Journal of
Molecular and Cellular Medicine, 5(3), 125–133.

Pistollato, F., Sumalla Cano, S., Elio, I., Masias Vergara, M., Giampieri, F., &
Battino, M. (2015). Plant-Based and Plant-Rich Diet Patterns during
Gestation: Beneficial Effects and Possible Shortcomings. Advances in
Nutrition, 6(5), 581–591. https://doi.org/10.3945/an.115.009126
Scala, I., Granese, B., Sellitto, M., Salomè, S., Sammartino, A., Pepe, A.,
Mastroiacovo, P., Sebastio, G., & Andria, G. (2006). Analysis of seven
maternal polymorphisms of genes involved in homocysteine/folate
metabolism and risk of Down syndrome offspring. Genetics in Medicine,
8(7), 409–416. https://doi.org/10.1097/01.gim.0000228206.21793.82

Shalaby, H. M. A. (2011). A study of new potential risk factors for Down

syndrome in Upper Egypt. Egyptian Journal of Medical Human Genetics,
12(1), 15–19. https://doi.org/10.1016/j.ejmhg.2011.02.009

Sparks, T. N., Griffin, E., Page, J., Pilliod, R., Shaffer, B. L., & Caughey, A. B.
(2016). Down syndrome: Perinatal mortality risks with each additional
week of expectant management: Perinatal mortality risk with Down
syndrome. Prenatal Diagnosis, 36(4), 368–374.
https://doi.org/10.1002/pd.4792

Gray, K.J., Wilkins-Haug, L.E. Have we done our last amniocentesis? Updates on
cell-free DNA for Down syndrome screening. Pediatr Radiol 48, 461–470
(2018). https://doi.org/10.1007/s00247-017-3958-y

Cereda, A., & Carey, J. C. (2012). The trisomy 18 syndrome. Orphanet journal of
rare diseases, 7, 81. https://doi.org/10.1186/1750-1172-7-81

Responsiveness of the Pediatric Evaluation of Disability Inventory—Computer

Adaptive Test in measuring functional outcomes for inpatient pediatric
rehabilitation. (2015). Developmental Medicine & Child Neurology, 57,
30–30. https://doi.org/10.1111/dmcn.47_12887

Williams, G. M., & Brady, R. (2021). Patau Syndrome. In StatPearls. StatPearls

Publishing.

Foley, C., & Killeen, O. G. (2018). Musculoskeletal anomalies in children with

Down syndrome: an observational study. Archives of Disease in Childhood,
archdischild–2018–315751. doi:10.1136/archdischild-2018-315751

Zago, M., Federolf, P. A., Levy, S. R., Condoluci, C., & Galli, M. (2019). Down
Syndrome: gait pattern alterations in posture space kinematics. IEEE
Transactions on Neural Systems and Rehabilitation Engineering, 1–1.
doi:10.1109/tnsre.2019.2926119
Silva, V., Campos, C., Sá, A., Cavadas, M., Pinto, J., Simões, P., …
Barbosa-Rocha, N. (2017). Wii-based exercise program to improve physical
fitness, motor proficiency and functional mobility in adults with Down syndrome.
Journal of Intellectual Disability Research, 61(8), 755–765. doi:10.1111/jir.12384

Dupre, C., & Weidman-Evans, E. (2017). Musculoskeletal development in

patients with Down syndrome. Journal of the American Academy of Physician
Assistants, 30(12), 38–40. doi:10.1097/01.jaa.0000526779.772

Skotko, B. G., & Tenenbaum, A. (2016). Down syndrome. In I. L. Rubin, J.

Merrick, & D. E. Greydanus (Eds.), Health care for people with intellectual and
developmental disabilities across the lifespan (pp. 739–750). New York: Springer.
https://doi.org/10.1007/978-3-319- 18096-0_63.

Al Sakhawi, R. S., & Elshafey, M. A. (2019). Effect of Core Stability Exercises

and Treadmill Training on Balance in Children with Down Syndrome:
Randomized Controlled Trial. Advances in Therapy.
doi:10.1007/s12325-019-01024-2

Maïano, C., Hue, O., Lepage, G., Morin, A. J. S., Tracey, D., & Moullec, G.
(2019). Do Exercise Interventions Improve Balance for Children and Adolescents
With Down Syndrome? A Systematic Review. Physical Therapy, 99(5), 507–518.
doi:10.1093/ptj/pzz012

Bush, D., Galambos, C., & Dunbar Ivy, D. (2020). Pulmonary hypertension in
children with Down syndrome. Pediatric Pulmonology. doi:10.1002/ppul.24687

Siama, A., Fountoulakis, P., Tsoukas, A., & Manolis, A. J. (2020). P270 Complex
cyanotic heart disease in adult patient with down syndrome accompanied by mild
pulmonary hypertension. European Heart Journal - Cardiovascular Imaging,
21(Supplement_1). doi:10.1093/ehjci/jez319.128

Magenis, M. L., Machado, A. G., Bongiolo, A. M., Silva, M. A. da, Castro, K., &
Perry, I. D. S. (2017). Dietary practices of children and adolescents with Down
syndrome. Journal of Intellectual Disabilities, 22(2), 125–134.
doi:10.1177/1744629516686571