Bataan National High School
Kagawaran ng Edukasyon
Rehiyon III
Lungsod ng Balanga, Bataan
TRISOMY 21: A CASE STUDY
SUBMITTED BY:
ALBA, FRINZ CHARLAN ONGKINGCO
ARENIEGO, GWEN MARESSE MAGNAYE
CALATA, RAZEL ELWYN TIGAS
CEREZO, PRINCESS ANNE TEOPENGCO
DANQUE, NIAN ONEAL MATILING
ESGUERRA, GABRIEL DENNIS ROBLES
LOPEZ, PAULINE FAYE BANZON
MOLINA, RONALYN RETOTA
RAMIREZ, JANUS RAPHAEL REYES
RAMOS, PAULINE ANNE ROQUE
TUNGOL, JOHN HENRY NISAY
ULARTE, MERYNN MARGARET GOZUN
SUBMITTED TO:
GIOVANNI D. DAVID
MARCH 2018
INTRODUCTION
Down syndrome is a genetic condition wherein a person has an extra
chromosome specifically the chromosome 21. Year 1866, John Langdon Down first
described the illness, and in 1959, it was clearly stated that chromosome 21 was the cause
of trisomy.
As seen in people with developmental disabilities, interpersonal communications
often differ from those of their "normal" counterparts, and it has been reported that children
with Down's syndrome typically have difficulties interacting with peers (Guralnick,
2002). Resulting from a chromosomal defect, Down's syndrome is a developmental
abnormality that is characterized by mental retardation which may involve developmental
delays and physical features typical of the disorder.
Flattened face, almond shaped eyes that slant up, a short neck, small ears, a tongue
that sticks out of the mouth, tiny white spots on the iris of the eye, small hand and feet, a
single line across the palm, poor muscle tone and shorter in height as children and adults,
with these physical features, one can simply identify an individual who suffers from Down
syndrome.
The 2% of the world’s population have Down syndrome. It is the most common
genetic condition in the United States of America. Here in the Philippines, according to
Manila Times (2014), one in every 800 babies born has Down syndrome or around 1,875
cases a year in the Philippines in a population of 1.5-million live births. The annual
mortality rate per 100,000 people from Down syndrome in Philippines has increased by
0.7% since 1990, an average of 0.0% a year.
Down syndrome has three types. The first one is the trisomy 21; the 95% of the
people with Down syndrome have trisomy 21. With this type of Down syndrome, there
three copies of chromosome 21 in each cell of the body. The second type is the
Translocation Down syndrome wherein an extra part or a whole extra chromosome 21 is
present but is translocated or attached to a different chromosome. The last one is the Mosaic
Down syndrome wherein only 2% of the population who has Down syndrome can be
affected. In this type, other cells have 3 copies of chromosome while the other cells have
only 2 copies.
Trisomy 21 is not contagious yet people are making ridicule to those who suffer
from this condition. Laughing about their looks and physical features and sometimes even
bullying them. There’s no one with Trisomy 21 who can live ordinary like normal are. That
is why we need to learn more about Down syndrome, they are not just people who have
extra copies of chromosome. They are people with disorder which leads to even more
complicated complications.
PEDIGREE ANALYSIS
MOTHER FATHER
SIDE SIDE
The main participant in this study was RR (not his real name), a 10-year old male
with Down's syndrome, who is currently a resident in Brgy. Cataning City of Balanga,
Bataan. This investigation is a case study that involved an interview.
The majority of Down syndrome cases are not hereditary. Usually the heredity of
the genes only occur during Translocation Down Syndrome Cases. The inherited cases
only occur when one of the parents is a carrier. In this case, the carrier will have 45
chromosomes instead of 46 but they will have all the genetic material of a person with 46
chromosomes.
In RR’s case, both of his parents were not carriers and the patient was diagnosed
with trisomy 21 after birth. The doctor also said that the case in which the patient had
trisomy 21 may be due to one of the ancestors of the family that may have carried the
affected chromosome.
Apart from this we also got the other dominant diseases in the family that may have
triggered trisomy 21 such as heart problems, diabetes, abortion, or repeated miscarriage.
We also put in consideration the age of the mother during pregnancy. There is a 25%
chance that a child may have the disorder if the mother’s age is greater than 42. In RR’s
case, his mother was already in her early 40’s when she got pregnant.
The mother’s side of the patient has a mother (which is the grandmother of the
patient) who does not have diabetes or homozygous recessive. While the father
(grandfather of the patient) who is heterozygous dominant that resulted to 3 of their
children being heterozygous as well, including the mother of the patient.
Because the mother of the patient has diabetes and the father is not affected, it is
possible that all 3 of her children may also be affected. Due to the Diabetes of the mother
it may have increased the risk of the condition. In this case the patient with Trisomy 21
also has a congenital heart disease in which case 40-50% of babies diagnosed with Down
Syndrome have one.
The patient has AV Canal defect wherein there's a hole between the heart's
chambers and problems with the valves that regulate blood flow in the heart.
MECHANISM OF THE DISEASE (PATHOGENESIS)
Normal Mitosis and Meiosis in Male:
STEM CELL 46
6
NEW STEM CELL
46 46 SPERMATOGONIUM
MITOSIS
6 6
PRIMARY SPERMATOCYTE 46
FIRST 6
MEIOSIS MEIOTIC DIVISION
23 23
SECONDARY SPERMATOCYTE
SECOND
MEIOTIC DIVISION
SPERMATIDS 23 23 23 23
23 23 23 23
SPERMATOZOA (MATURE)
Normal Mitosis and Meiosis in Female:
STEM CELL 46
6
OOGONIUM
46 46 NEW STEM CELL
MITOSIS
6 6
PRIMARY OOCYTE 46
6 FIRST
MEIOTIC DIVISION
MEIOSIS
23 23
POLAR BODY SECONDARY
OOCYTE
SECOND
MEIOTIC DIVISION
23 23 23
POLAR BODIES
23
MATURE OVUM
95% of all Down Syndrome comes from Trisomy 21 or free trisomy. This is where
non-typical cellular division occurs in either the egg or sperm, in which 90% of cases
originates from the egg (Lashley, 2006). The figure below shows the non-disjunction in
cell division of male and female that cause Trisomy 21:
NON-DISJUNCTION
IN MEIOSIS I OF
SPERMATOGENESIS STEM CELL 46
MITOSIS 6
NEW STEM CELL
46 46 SPERMATOGONIUM
6 6
PRIMARY SPERMATOCYTE 46
FIRST 6
MEIOTIC DIVISION
MEIOSIS
22 24
SECONDARY SPERMATOCYTE
SECOND
MEIOTIC DIVISION
SPERMATIDS 22 22 24 24
22 22 24 24
SPERMATOZOA (MATURE)
SPERM)
NON-DISJUNCTION
IN MEIOSIS II OF
SPERMATOGENESIS
STEM CELL 46
MITOSIS 6
NEW STEM CELL
46 46 SPERMATOGONIUM
6 6
PRIMARY SPERMATOCYTE 46
FIRST 6
MEIOTIC DIVISION
MEIOSIS
23 23
SECONDARY SPERMATOCYTE
SECOND
MEIOTIC DIVISION
SPERMATIDS 22 24 22 24
22 24 22 24
SPERMATOZOA (MATURE)
SPERM)
NON-DISJUNCTION
IN MEIOSIS I OF
OOGENESIS
STEM CELL 46
6
OOGONIUM
46 46 NEW STEM CELL
MITOSIS
6 6
PRIMARY OOCYTE 46
6 FIRST
MEIOTIC DIVISION
MEIOSIS
22 24
POLAR BODY SECONDARY
OOCYTE
SECOND
MEIOTIC DIVISION
22 22 24
POLAR BODIES
24
MATURE OVUM
NON-DISJUNCTION
IN MEIOSIS I OF
OOGENESIS
STEM CELL 46
6
OOGONIUM
46 46 NEW STEM CELL
MITOSIS
6 6
PRIMARY OOCYTE 46
6 FIRST
MEIOTIC DIVISION
MEIOSIS
24 22
POLAR BODY SECONDARY
OOCYTE
SECOND
MEIOTIC DIVISION
24 24 22
POLAR BODIES
22
MATURE OVUM
NON-DISJUNCTION
IN MEIOSIS II OF
OOGENESIS
STEM CELL 46
6
OOGONIUM
46 46 NEW STEM CELL
MITOSIS
6 6
PRIMARY OOCYTE 46
6 FIRST
MEIOTIC DIVISION
MEIOSIS
23 23
POLAR BODY SECONDARY
OOCYTE
SECOND
MEIOTIC DIVISION
22 24 22
POLAR BODIES
24
MATURE OVUM
NON-DISJUNCTION
IN MEIOSIS II OF
OOGENESIS
STEM CELL 46
6
OOGONIUM
46 46 NEW STEM CELL
MITOSIS
6 6
PRIMARY OOCYTE 46
6 FIRST
MEIOTIC DIVISION
MEIOSIS
23 23
POLAR BODY SECONDARY
OOCYTE
SECOND
MEIOTIC DIVISION
24 22 24
POLAR BODIES
22
MATURE OVUM
FINDINGS
Down Syndrome, also known by the karyotype 47,XX,+21 for females and
47,XY,+21 for males or trisomy 21, is a genetic disorder caused by a microscopically
demonstrable chromosomal aberration. It is caused by triplicate state (trisomy) of all or a
critical portion of chromosome 21. The term Down syndrome comes from Dr. Langdon
Down, the doctor who first described the collection of physical symptoms in 1866. It was
not until 1959 that the cause of Down syndrome (the presence of an extra #21
chromosome) was identified.
Also, it is associated with intellectual disability, a characteristic facial appearance,
and weak muscle tone (hypotonia) in infancy. All affected individuals experience
cognitive delays, but the intellectual disability is usually mild to moderate.Life
expectancy among adults with Down syndrome is about 60 years, though average
lifespan varies.
Trisomy 21 is the most common genetic cause of mental retardation and one of
the few aneuploidies compatible with post-natal survival. The vast majority of meiotic
errors leading to the trisomic condition occur in the eggs. Besides mental retardation,
present in every individual with Down Syndrome (DS) , trisomy 21 is associated with
more than 80 clinical traits including congenital heart disease, duodenal stenosis or
atresia, imperforate anus, Hirschprung disease, muscle hypotonia, immune system
deficiencies, increased risk of childhood leukemia, gastroesophageal reflux, which is a
backflow of acidic stomach contents into the esophagus, and celiac disease which is an
intolerance of a wheat protein called gluten and early onset Alzheimer’s disease.
Most cases of Down syndrome result from trisomy 21, which means each cell in
the body has three copies of chromosome 21, instead of the usual two copies.Less
commonly, Down syndrome occurs when part of chromosome 21 becomes attached to
another chromosome during the formation of reproductive cells (eggs and sperm) in a
parent or very early in fetal development.
Affected people have two normal copies of chromosome 21 plus extra material
from chromosome 21 attached to another chromosome, resulting in three copies of
genetic material from chromosome 21. Affected individuals with this genetic change are
said to have Translocation Down syndrome. People with Translocation Down syndrome
can inherit the condition from an unaffected parent. The parent carries a rearrangement of
genetic material between chromosome 21 and another chromosome. This rearrangement
is called a Balanced Translocation. No genetic material is gained or lost in a balanced
translocation, so these chromosomal changes usually do not cause any health problems.
However, as this translocation is passed to the next generation, it can become unbalanced
People who inherit an unbalanced translocation involving chromosome 21 may have
extra genetic material from chromosome 21, which causes Down syndrome.
A very small percentage of people with Down syndrome have an extra copy of
chromosome 21 in only some of the body's cells. In these people, the condition is called
Mosaic Down syndrome. Like trisomy 21, mosaic Down syndrome is not inherited. It
occurs as a random event during cell division early in fetal development. As a result,
some of the body's cells have the usual two copies of chromosome 21, and other cells
have three copies of this chromosome.
Most cases of Down syndrome are not inherited. When the condition is caused by
trisomy 21, the chromosomal abnormality occurs as a random event during the formation
of reproductive cells in a parent. The abnormality usually occurs in egg cells, but it
occasionally occurs in sperm cells. An error in cell division called nondisjunction which
results in a reproductive cell with an abnormal number of chromosomes. For example, an
egg or sperm cell may gain an extra copy of chromosome 21. If one of these atypical
reproductive cells contributes to the genetic makeup of a child, the child will have an
extra chromosome 21 in each of the body's cells.
About half of babies with Down syndrome have heart defects. Some defects are
minor and may be treated with medications, while others may require surgery. All babies
with Down syndrome should be examined by a pediatric cardiologist. This is a doctor
who specializes in heart diseases of children. Babies with Down syndrome should also
have an echocardiogram. This is a procedure that evaluates the structure and function of
the heart by using sound waves recorded on an electronic sensor that produce a moving
picture of the heart and heart valves. This exam and test should be done in the first two
months of life, so that any heart defects can be treated.
Some babies with Down syndrome are born with intestinal malformations that
require surgery. Children with Down syndrome are at increased risk for visual
impairment. Common visual problems include crossed eyes, near- or farsightedness, and
cataracts. Most visual problems can be improved with glasses, surgery, or other
treatments. A pediatric ophthalmologist should be consulted within the first year of life.
This is a doctor who specializes in comprehensive eye care and provides examinations,
diagnosis, and treatment for a variety of eye disorders.
They may also have hearing loss because of fluid in the middle ear, a nerve
defect, or both. All children with Down syndrome should have regular vision and hearing
examinations so any problems can be treated before they hinder development of language
and other skills.
Children with Down syndrome are at increased risk for thyroid problems and
leukemia. They also tend to have many colds, as well as bronchitis and pneumonia.
Children with the said disorder should receive regular medical care, including childhood
immunizations. The National Down Syndrome Congress publishes a "Preventive
Medicine Checklist" that outlines which check-ups and medical tests are recommended at
various ages.
In our participant’s case, he acquired a heart disease called Atrioventricular Canal
Defect, sometimes called Endocardial Cushion Defect or Atrioventricular Septal Defect,
Atrioventricular Canal Defect. Atrioventricular canal defect allows extra blood to flow to
the lungs. The extra blood forces the heart to overwork, causing the heart muscle to
enlarge (MayoClinic, 1998-2018).
A child with Down syndrome may have eyes that slant upward and small ears that
may fold over slightly at the top. The child's mouth may be small, making the tongue
appear large. The child's nose also may be small, with a flattened nasal bridge. Some
babies with Down syndrome have a short neck and small hands with short fingers. Rather
than having three "creases" in the palm of the hand, a child with Down syndrome usually
has one single crease that goes straight across the palm, and a second crease that curves
down by the thumb. The child or adult with Down syndrome is often short and has
unusual looseness of the joints. Most children with Down syndrome will have some, but
not all, of these features. Common physical signs of Down syndrome includes:
1)Decreased or poor muscle tone 2)Short neck with excess skin at the back of the neck
3)Flattened facial profile and nose 4) Small head, ears, and mouth 5)Upward slanting
eyes, often with a skin fold that comes out from the upper eyelid and covers the inner
corner of the eye 6) White spots on the colored part of the eye (called Brushfield spots)
7)Wide, short hands with short fingers 8)A single, deep, crease across the palm of the
hand 9)A deep groove between the first and second toes
In addition, physical development in children with Down syndrome is often
slower than development of children without Down syndrome. For example, because of
poor muscle tone, a child with Down syndrome may be slow to learn to turn over, sit,
stand, and walk. Despite these delays, children with Down syndrome can learn to
participate in physical exercise activities like other children. It may take children with
Down syndrome longer than other children to reach developmental milestones, but they
will eventually meet many of these milestones.
It is proven that children with Down Syndrome can still go to school. It is because
special programs beginning in preschool years are now available which helps children
with Down Syndrome develop skills as fully as possible. Along with benefiting from
early intervention and special education, many children can be integrated into the regular
classroom, to some extent. Since there are special work programs designed for adults
with Down syndrome, many can hold regular jobs. Today, an increasing number of adults
with Down syndrome live semi-independently in community group homes. They take
care of themselves, participate in household chores, develop friendships, partake in
leisure activities, and work in their communities.
Some people with Down syndrome can even marry. Although there have been
rare exceptions, most men with Down syndrome cannot father a child. In any pregnancy,
a woman with Down syndrome has a 50/50 chance of conceiving a child with Down
syndrome, although many of the pregnancies are miscarried.
There is no cure for Down syndrome. Doctors are not certain how to prevent the
chromosomal error that causes Down syndrome. To date, there is no reason to believe
that a parent could have done anything to cause or prevent the birth of a baby with Down
syndrome. However, a recent study suggests that some women who have had a baby with
Down syndrome had an abnormality in how their body metabolizes, or processes, the B
vitamin folic acid. If confirmed, this finding may provide yet another reason why all
women who might become pregnant should take a daily multivitamin containing 400
micrograms of folic acid. This has been shown to reduce the risk for certain birth defects
of the brain and spinal cord.
Some people claim that various high-dose vitamins given to children with Down
syndrome will improve the mental performance and lessen the degree of intellectual
disability. To date, however, no medical studies have proved that this actually works. It is
important for new families to talk with their physician, other families, and national Down
syndrome support agencies to learn what to expect with Down syndrome and to learn
about things that may be helpful in raising a child with Down syndrome. However,
children with Down syndrome would benefit from early medical assistance and
developmental interventions beginning during infancy. Children with Down syndrome
may benefit from speech therapy, physical therapy and occupational therapy. They may
receive special education and assistance in school.
CONCLUSION AND RECOMMENDATIONS
Trisomy 21 or Down syndrome, the most common genetic disorder, deals
with an extra chromosome. This condition can be inherited, if one of the parents has a
family history with Down syndrome then the possibility of having a child with this
condition is one out three children. While having both parents who have trisomy 21 in their
genes have a high possibility of developing one to two children with Down syndrome. This
condition is not contagious yet can be extremely harmful if there is an existing gene from
one of the parents containing an extra chromosome.
In our participant’s case, the age of the mother had a big factor. For, if none of the
parents have a history with Down syndrome, then the age of the mother can be a reason.
Having a child with the age of 35 and above have a higher risk of having a Down syndrome
or even other disorders. Because of the older age, one’s pregnancy can be difficult and can
experience other abnormalities and malfunction.
Different factors and reason why there is a non-disjunction happening in an
individual’s genetic material. This prevents them to separate, making an extra copies of
chromosome 21 and resulting into a Down syndrome condition. Trisomy 21 often and may
also lead to different complications such as Leukemia, Thrombocytopenia, Intellectual
Disability, Autism, Alzheimer’s Disease, different Heart Disease and many more that may
affect their growth and Endocrine system.
In our participant’s case, he acquired a heart disease called Atrioventricular Canal
Defect, sometimes called Endocardial Cushion Defect or Atrioventricular Septal Defect,
Atrioventricular Canal Defect. Atrioventricular canal defect allows extra blood to flow to
the lungs. The extra blood forces the heart to overwork, causing the heart muscle to
enlarge (MayoClinic, 1998-2018).
Untreated, Atrioventricular Canal Defect can cause heart failure and high blood
pressure in the lungs. Doctors generally recommend surgery during the first year of life to
close the hole in the heart and to reconstruct the valves (MayoClinic, 1998-2018).
Although Trisomy 21 or Down syndrome has no cure, there are some therapy and
treatment for the complications. People with Down syndrome may look different from a
normal person. They will need a special love, care and support, they may have an extra
chromosome 21 but that is what makes them special.
As a recommendation, since we limit our participants in Balanga and we found one
in Brgy. Cataning City of Balanga, Bataan. We recommend the future researchers to study
the most occurring side effect in an individual having Trisomy 21 in Bataan. It can be a
heart disease, hearing problems, intestinal problems, celiac disease, eye problems, thyroid
dysfunction, skeletal problems or infectious disease.
We also recommend the future researchers to study the most effective treatment or
therapy in a certain side effect of Trisomy 21.
ACKNOWLEDGEMENT
On the very outset of this case study, we would like to extend our sincere and
heartfelt obligations towards all the personages who have helped us in this endeavor.
Without their active guidance, help, cooperation and encouragement, we would not have
made headway in this study.
We are indebted to Sir Giovanni David for conscientious guidance and
encouragement to accomplish this study.
We are extremely thankful and pay our gratitude to the father of Merynn Ularte for
his valuable guidance and support for completion of this study.
The information shared by Dr.Joseph Quan is deeply appreciated and useful during
the study.
We also acknowledge with a deep sense of reverence, our gratitude towards the
family of the respondent for giving us an opportunity to finish our study.
At last but not least gratitude goes to our parents who has always supported
us morally as well as economically.
Any omission in this brief acknowledgement does not mean lack of gratitude and
to God be all the glory.
REFERENCES:
Antonarakis SE, Lyle R, Dermitzakis ET, Reymond A, Deutsch S. (2004) Chromosome
21 and
Down syndrome: from genomics to pathophysiology. Nat Rev Genet. 5(10):725-38.
Arque G, Casanovas A, Dierssen M (2013)Dyrk1A Is Dynamically Expressed on
Subsets of
Motor Neurons and in the Neuromuscular Junction: Possible Role in Down Syndrome
PLoS
One. 8(1):e54285
Block A, Dhanasekaran AR, Ahmed MM, Gardiner KJ. (2014)Abnormal Protein
Profiles in
Hippocampus of Mouse Models of Down Syndrome: Similarities with Alzheimer’s
Disease. J
Alzheimers Dis Parkinsonism 4: 138.
Chapman RS, Hesketh LJ. (2000) Behavioral phenotype of individuals with Down
syndrome.
Ment Retard Dev Disabil Res Rev.;6(2):84-95.
Dierssen M. (2012) Down syndrome: the brain in trisomic mode. Nat Rev
Neurosci.:844 -58.
Dykens EM (2007) Psychiatric and behavioral disorders in persons with Down
syndrome
Ment. Retard. Dev. Disabil. Res. Rev., 13: 272–278
Einfeld SL, Brown R (2010) Down Syndrome—New Prospects for an Ancient
Disorder JAMA
303(24):2525-2526
Epstein C. Down Syndrome1(1995) In: Scriver CR, Beaudet AL Sly WS, Valle D, eds.
The
metabolic and molecular bases of inherited disease. New York: McGraw-Hill 749-94.
Farriols Danés C (2012). Specific aspects of ageing in Down’s syndrome. Rev Med Int
Sindr
Down. 16(1):3-10
Fillat C, Bofill-De Ros X., Santos M., Martín ED, Andreu N, Villanueva E, d'Amico
D, Dierssen
M, Altafaj X (2014) Identification of key genes involved in Down's syndrome
pathogenesis by
gene therapy. Rev Med Int Sindr Down 18(2):21-8
Gardiner K, Davisson MT, Pritchard M, Patterson D, Groner Y, Crnic LS,Antonarakis
S,
Mobley W (2005) Report on the 'Expert Workshop on the Biology of Chromosome 21:
towards
gene-phenotype correlations in Down syndrome', held June 11-14, 2004, Washington
D.C.
Cytogenet Genome Res.108(4):269-77.
Letourneau A,Santoni FA,Bonilla X, Sailani MR, Gonzalez D, Kind J, Chevalier C,
Thurman R,
Sandstrom RS, Hibaoui Y, Garieri M, Popadin K, , Falconnet E, Gagnebin M, Gehrig
C,
Vannier A, Guipponi M, Farinelli L, Robyr D, Migliavacca E, Borel C, Deutsch S, Feki
A,
Stamatoyannopoulos J A, Herault Y, van Steensel B, Guigo R & Antonarakis SE.
(2014)
Domains of genome-wide gene expression dysregulation in Down's syndrome. Nature
508
(7496):345-50
Lott IT (2012) Neurological phenotypes for Down syndrome across the life span. Prog
Brain
Res. 97: 101–121.
Makary A, Testa R, Einfeld SL, Tonge BJ, Mohr C, Gray KM (2014) The association
between
behavioural and emotional problems and age in adults with Down syndrome without
dementia:
Examining a wide spectrum of behavioural and emotional problems. Res Dev Disabil.
35(8):1868-77
Neri G, Opitz JM. (2009) Down syndrome: Comments and reflections on the 50th
anniversary
of Lejeune’s discovery. Am J Med Genet Part A 149A:2647–2654
Nespoli L, Burgio GR, Ugazio AG, Maccario R (1993) Immunological features of
Down's
syndrome: a review. J Intellect Disabil Res. 37,543-51.
Oliver C, Crayton L, Holland AJ, Hall S. (2000). Acquired cognitive impairments in
adults with
Down syndrome: Effects on the individual, carers and services. AJMR, 105, 455-465.
Patterson D, Costa AC (2005) Down syndrome and genetics - a case of linked histories.
Nat
Rev Genet 6(2):137-47.
Rachidi M, Lopes C. (2007) Mental retardation in Down syndrome: from gene dosage
imbalance to molecular and cellular mechanisms.Neurosci Res. 2007 Dec;59(4):349-
69
Roizen NJ, Patterson D. (2003) Down's syndrome. Lancet 361(9365):1281-9
Ronan A,Fagan K, Christie L, Conroy J, Nowak NJ, Turner G.(2007) Familial 4.3 Mb
duplication of 21q22 sheds new light on the Down syndrome critical region. J Med
Genet.44(7):448-51
Shapiro BL (1994) The environmental basis of the Down Syndrome Phenotype.
Developmental
Medicine and Child Neurology, 36, 84-90.
Atrioventricular Canal Defect. (n.d.). Retrieved March 11, 2018, from
https://www.mayoclinic.org/diseases-conditions/atrioventricular-canal-defect/symptoms-
causes/syc-20361492
Down Syndrome Facts. (n.d.). Retrieved February 11, 2018, from
https://www.ndss.org/about-down-syndrome/down-syndrome-facts/
CDC. (n.d.). Down Syndrome. Retrieved March 11, 2018, from
https://www.cdc.gov/ncbddd/birthdefects/downsyndrome.html
Down Syndrome (Trisomy 21). (n.d.). Retrieved February 18, 2018, from
http://www.stanfordchildrens.org/en/topic/default?id=down-syndrome-trisomy-21-90-
P02356
Down Syndrome. (n.d.). Retrieved February 18, 2018, from
https://ghr.nlm.nih.gov/condition/down-syndrome
Down Syndrome: Trisomy 21. (n.d.). Retrieved February 18, 2018, from
http://americanpregnancy.org/birth-defects/down-syndrome/
Sommer, C., & Henrique, S. F. (2007-2008). Trisomy 21 and Down syndrome - A short
review. Retrieved February 18, 2018, from
https://pdfs.semanticscholar.org/d14b/b335ec8e7319839916ae80ae9802e512df05.pdf
Down Syndrome (Trisomy 21). (n.d.). Retrieved February 18, 2018, from
http://www.stanfordchildrens.org/en/topic/default?id=down-syndrome-trisomy-21-90-
P02356
Down Right Cute. (n.d.). Retrieved March 11, 2018, from
https://downrightcute.com/2017/03/pathophysiology/
