Down Syndrome is one of the most common genetic disorders in India. In this article, we delve into a deeper understanding of Down syndrome, its types and causes, genetic mechanisms, associated medical conditions, genetic tests, and genetic counseling.
Context
- Introduction
- Phenotypes of Down Syndrome
- Genetics and types of Down syndrome
1. T21
2. Mosaic Down syndrome
3. Translocation Down syndrome - Possible medical complications
- Genetic testing
- Importance of early diagnosis
- Positives in Down syndrome
- Scientific ways to improve quality of life
- Phenotypes of Down Syndrome
Introduction
Down syndrome is a congenital genetic disorder that affects a baby’s intelligence,
growth and development, heart, blood(Li et al., n.d.), brain, and hormones (Hernandez
& Fisher, 1996). It is caused either by chromosomal numerical or structural
abnormalities, and fusions between specific genomic regions that lead to
overexpression of certain genes (Li et al., n.d.). It is one of the most common genetic
disorders in India.
Down syndrome is preventable with current advanced genetic technologies. It can be
diagnosed during pregnancy (antenatal period) using prenatal genetic screening and
diagnostics that help parents make informed pregnancy decisions (Dungan et al., 2023).
Though Down syndrome is associated with many life-threatening medical conditions, its
life expectancy has now improved to above 50 years (Antonarakis et al., 2020). In
addition to life expectancy, the quality of life of individuals with Down syndrome is
improved by genetic counseling, special schools, early interventions, and healthcare
management.
Phenotypes of Down Syndrome
Down syndrome is characterized by various phenotypic changes (Gensous et al.,
2019)in the baby including,
- Upper palpebral fissures: The baby’s eyes appear to slant upward.
- Hypertelorism: There is an increased distance between the eyes.
- Macroglossia: The tongue is unusually large.
- Protruding tongue: The baby frequently keeps their tongue outside their mouth.
- Brachycephaly: The back of the baby’s head appears flattened.
- Clinodactyly: The little finger is small and may curve inward.
- Single palmar crease: A single crease is present across the palm.
- Broad nasal bridge: The nasal bridge is wider than usual.
- Low-set ears: The ears are positioned below the line of the eyes.
- Sandal gap: There is an increased gap between the first and second toes.
It is important to know that though these physical characteristics are common among
children with Down syndrome, they also overlap with other genetic conditions. To
confirm the diagnosis further medical and genetic testing would be advised.
Genetics and types of Down syndrome
There are 46 chromosomes or 23 pairs of chromosomes in human body cells. Changes
in the number of chromosomes, either extra copies or missing one pair of
chromosomes, and changes in the structure of chromosomes lead to genetic disorders,
syndromes, or dysmorphisms.
Down syndrome results from an extra copy of the 21 st chromosome or structural
changes in the 21 st chromosome. Based on this, down syndrome is classified into three
types as follows:
1) Trisomy 21
2) Mosaic Down syndrome
3) Translocation Down syndrome
1. Trisomy 21
Non-disjunction, an incorrect separation of chromosomes to each cell during cell
division results in an extra copy of chromosome 21 in the embryo . This chromosomal
condition is known as Trisomy 21. Trisomy 21 type of Down syndrome is the most
common type of Down syndrome among other types of this syndrome. It leads to gene
dosage imbalance resulting in overexpression of certain genes in DSCR (Down
Syndrome Critical Region) which causes various medical problems.
2. Mosaic Down syndrome
Chromosomal changes in chromosome 21 are found only in a few cells and the other
cells have normal copies or structures of chromosome 21. This genetic condition is
known as mosaicism. Children or adults with mosaic Down syndrome express milder
symptoms and medical conditions (Clarke et al., n.d.).
3. Translocation Down syndrome
Translocation of certain regions between chromosomes 14 and 21 leads to extra
genetic material, which results in the manifestation of characteristics of Down
syndrome. This type of chromosomal rearrangement is known as unbalanced or
Robertsonian translocation (Clarke et al., n.d.). Compared to the other two types of
Down syndrome, this form of Down syndrome is found in 3-4% of cases.
Possible medical complications
Gene dosage due to extra genetic material in chromosome 21 results in medical
complications in children and adults with Down syndrome (Li et al., n.d.). Despite their
risk of a wide range of medical complications, their need for healthcare and genetic
counseling varies. Some of the most common medical complications in Down syndrome
are cardiovascular problems, and endocrine issues including hypothyroidism, dental
problems, obesity, developmental delay, speech delay, intellectual disability, vision
problems, Alzheimer’s, autistic traits, etc. (Bull et al., 2011). It is important to understand
that not all individuals with Down syndrome express all medical problems.
Genetic testing
Advancements in the genetic field have led to the application of genetic theories and
technologies in the medical field to diagnose certain genetic disorders in individuals,
families, couples, or parents. Such genetic application in patient care helps geneticists
and medical professionals diagnose Down syndrome prenatally(NIPS, n.d.) (before
birth, during pregnancy) and postnatally (after birth) (Agarwal Gupta & Kabra, 2014a).
Conventionally, the down syndrome can be diagnosed in children, or adults using
cytogenetic technology also called cytogenetic tests like karyotyping, and FISH
(Fluorescent In-Situ Hybridization) (Morris et al., 2012). Among these karyotyping is the
most common cytogenetic test to confirm Down syndrome. Chromosomes are collected
from their blood by performing various scientific steps, stained using a specific dye, and
spread in slides. Such slides are viewed under a light microscope and using certain
software chromosomes are arranged and analyzed for numerical and structural
changes.
In this case, the cytogeneticist carefully looks for an extra number of chromosomes 21
and translocation between chromosomes 14 and 21. Furthermore, they confirm if such
chromosomal abbreviations are found in all cells or only in a few cells (mosaic). In
addition to cytogenetic tests, certain molecular genetic tests like QF-PCR, and CMA
(chromosomal microarray) confirm Down syndrome and its types.
Importance of early diagnosis
Early genetic diagnosis helps parents and their families to reduce financial and hospital
burdens and psycho-social issues like facing stigma and stereotypes for giving birth to a
genetically impaired child. Advancements in the genetic field enable healthcare
providers to find certain genetic disorders during pregnancy and help parents make
informed pregnancy decisions.
Down syndrome can be diagnosed during pregnancy using prenatal genetic screening,
such as Non-invasive Prenatal Genetic Screening/Testing (NIPS/NIPT) (Gekas et al.,
2014), amniocentesis, chorionic villi sampling, cordocentesis, etc., which are different
types of medical procedures to collect fetal samples that have DNA or genetic material.
The collected fetal samples are sent to a genetic company where geneticists perform a
wide range of experiments to confirm Down syndrome.
If the genetic test confirms Down syndrome in the growing baby, genetic counselors
educate the parents about their fetus's genetic test report about Down syndrome and
help them to decide whether to carry on the pregnancy or abort it. Based on the
information provided by the genetic counselor, parents can decide about pregnancy
(Leach, 2016).
Such pregnancy-related decisions would help the parents and their family to know their
risk for Down syndrome in future pregnancies, and any other chromosomal aberrations,
reduce their financial burden and improve their family’s quality of life.
Positives in Down syndrome
Though people with Down syndrome are associated with many challenges in mind and
body, they can achieve success in life in their chosen field with proper guidance and
support. There are many achievers in the world with Down syndrome whose
contribution to society is acclaimed worldwide.
- Pablo Pineda is a Spanish actor and the first university graduate in Europe
with Down syndrome. He graduated BA in educational psychology
(https://en.wikipedia.org/wiki/Pablo_Pineda) - Sujeet Desai is a musician and motivator born with Down syndrome in New
York, USA. He is a music graduate of the USA and is skilled in playing seven
musical instruments. In addition to his success as a musician, he is also an
ambassador of Down Syndrome International, London, and the Global Down
Syndrome Foundation, USA. (https://www.sujeetdesai.com/) - Collette Divitto, founder of Collettey’s Cookies. He graduated from Clemson
University in South Carolina. Down syndrome did not stop him from being an
entrepreneur. (https://en.wikipedia.org/wiki/Collette_Divitto) - Megan Bomgaars is a reality star, motivational speaker, and public speaker
known for her appearance in a reality series named “Born This Way”. She is a
graduate of a film studio from the University of Colorado and co-founded a tie-
dyed clothing line. (https://www.facebook.com/MeganGBomgaars/)
Scientific ways to improve quality of life
Every successful personality with Down syndrome mentioned above is achieved with
the help of their mother. It is in the hands of parents who have a child or individual with
Down syndrome to understand, manage, and improve their challenges to make them
productive in society.
According to recent research, developmental therapies to improve their motor skills,
speech therapy, annual medical check-ups that mainly focus on heart, thyroid profiles,
and growth profiles in infants, sex education, special schools, special classes for their
interested skills, college education, etc. help individuals with Down syndrome improve
their quality of life (Agarwal Gupta & Kabra, 2014b; Bull et al., 2011b).
Genic Hereditary Care, a genetic counseling clinic encourages parents or family who
have a child or a person with Down syndrome to engage them in mild sports with
neighbors or siblings, give fine motor exercises, assist and make them do their regular
activities, teach them about good and bad touch, girl children should be taught about
her menstrual cycle and hygiene, teach them the skills that they are interested in, it can
be music or dance or art, etc.
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