DOWN SYNDROME
(TRISOMY 21)

Disease

DOWN SYNDROME
(TRISOMY 21)

Down Syndrome is a type of chromosomal aberration caused by a triplicate state of all or a critical portion of chromosome 21 "Trisomy 21". Commonly caused by a microscopically genetic chromosomal aberration which results in an extra partial or full copy of chromosome 21. It is one of the most frequent causes of learning disabilities among children.

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People affected by Down Syndrome

Frequency

Down syndrome occurs in about 1 in 700 newborns. The chance of having a child with this condition increases as a woman gets older. In the Philippines, down syndrome frequently occurs 1 in 800 births, or around 1,875 babies, are born with the disorder each year.

Inheritance

Down syndrome is mostly inherited in an autosomal dominant manner, however there are also cases that it occurs in an isolated case which is due to the error in replication of chromosomes.

Brief Summary

History of Disease

1515 - The earliest known depiction of a person with Down syndrome were two angels in a Flemish painting entitled, “The Adoration of the Christ Child,” by the painter named, Jan Joest of Kalkar.

1866 - John Langdon Down, an English physician, published in his scholarly work an accurate description of a person with Down syndrome, but he misunderstood how Down syndrome arises. The term “ mongoloid” was used to describe the condition of the affected children sharing similar physical features from the Mongolian race of Blumenbach.

1959 - Jérôme Lejeune, a French physician, together with Gautier, and Turpin published an article which discusses and explains that people having down syndrome are caused by an additional chromosome in a human karyotype which results to having a total of 47 chromosomes instead of having the normal or standard karyotype of 23 pairs. The extra chromosome was very small, and was thought at the time to be the second smallest chromosome. This was therefore a proof that Down syndrome was caused by the trisomy of chromosome 21 , which is in fact another name for this syndrome.

History of Disease

Pathogenesis

Achondroplasia is caused by a mutation in the FGF3 gene in chromosome 4 at 4p 16.3. This mutation causes a decreased production of fibroblast growth factor receptor 3 which is crucial in the conversion of cartilage into bone which is vital in the proper development of a person. This mutation is inherited in an autosomal dominant manner. More than 80 percent of people with achondroplasia have parents with normal characteristics and are born with achondroplasia due to a recent (de novo) gene modification (mutation).

Pathogenesis

Nondisjunction
Prior to or before the formation of the zygote, a sperm’s or egg’s 21st pair of chromosomes fail to divide. Thus, results in the presence of the entire copy of chromosome 21 is found in a genome or in all the cells of the fetus.

Translocation
Some portion of chromosome 21 is translocated to other chromosomes, usually, translocation with 14 and 15 are reported commonly.

Mosaicism
The extra chromosome spontaneously appears as the embryo develops and present in some but not all cells of the body.

Most of the time, trisomy 21 down syndrome isn't inherited. The error in cell division during the early development of the fetus is the common cause in which the chromosomal abnormality occurs as a random event during the formation of reproductive cells in a parent. Usually nondisjunction of chromosome 21 during meiosis. There is a small chance of about 3-4% that the translocation in down syndrome can be passed inherited by the child from the parent. In addition, mosaic Down syndrome is not inherited as well. The trisomy 21 karyotype is present in 93 to 95% of people with Down syndrome; a further 3 to 4% exhibit translocation anomalies and 1 to 3% are mosaic. Heredity is not a factor in Down Syndrome.

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Mutated chromosome by Down Syndrome

Symptoms

poor or decreased muscle tone

having excess skin at the back of the

neck

flattened nose and other facial profile

smaller head, ears, and mouth

upward slanting eyes, often with a skin fold that comes out from the upper eyelid and covers the inner corner of the eye

white spots on the colored part of the eye (called brushfield spots)

wide, short hands with short fingers

a single, deep, crease across the palm of the hand

Social Concerns

People having Down syndrome may feel left behind or be put off taking part because it is hard to find welcoming and accessible activities. Often caused by other people’s ignorance, misunderstanding or fear rather than a deliberate desire to exclude.

Treatment

Treatments and managements for Down syndrome are based on a person's physical and intellectual challenges.

Physical, Occupational, Speech, and Educational Therapy
Several areas of a child’s development including motor skills, language, intellectual abilities, and social and adaptive skills are affected when having down syndrome.

Regular screening & testing
For monitoring of vision problems, hearing loss, ear infections, hypothyroidism, and other medical conditions.

Surgery
Individuals with down syndrome having cardiac and gastrointestinal anomalies may need corrective surgery soon immediately after birth.

Genetic Counseling
For parents, it is important to get advice about the incidences of Down syndrome, advancements in diagnosis, and the protocols for care and treatment of babies born with Down syndrome.

Special education & training
These are best offered for children with intellectual and developmental disabilities.

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Treatment for Down Syndrome

Clinical Trials

Title:

Safety, efficacy, and tolerability of memantine for cognitive and adaptive outcome measures in adolescents and young adults with Down syndrome: a randomized, double-blind, placebo-controlled phase 2 trial

Intervention Phase:

A pilot trial in young adults with Down syndrome, memantine (a drug approved for Alzheimer's disease) showed a significant effect on a secondary measure of episodic memory.

Procedure:

Participants were randomly assigned (1:1) to receive either memantine (20 mg/day orally) or placebo for 16 weeks.

Goal:

To test whether memantine would improve episodic memory in adolescents and young adults with Down syndrome.

Further details at:

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00369-0/fulltext

Clinical Trials

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