DOWN SYNDROME

Dedet Steavano, Yuda Perdana Putra Simbolon,

Muhammad iqsan, Cut Apriliza Novita, Dedy
Saputra, Tari Adrian, Ben Ben Irwandi,
Shilvanna litania, Dina Afiani, Tamara Christine
 Two different hypotheses have been proposed
to explain the mechanism of gene action in
Down syndrome:
• Developmental instability (ie, loss of
chromosomal balance)
• Gene-dosage effect.
According to the gene-dosage effect
hypothesis, the genes located on chromosome
21 have been overexpressed in cells and
tissues of Down syndrome patients, and this
contributes to the phenotypic abnormalities
ETIOLOGY
Down syndrome is caused by the following 3
cytogenic variants:
• Three full copies of chromosome 21
• Chromosomal translocation that results in 3
copies of the critical region for Down
syndrome
• Mosaicism
• Down syndrome (DS) is caused by
trisomy of human chromosome
21 (Hsa21) (94%)

• Robertsonian translocation causes

a type of Down Syndrome (3.3%)

• 2.4% have mosaicism with normal

and trisomy 21 cell lines (and Non-disjunction
usually have much milder
features because of the
Non-disjunction
presence of the normal cells); -
occurs postzygotically
• A free trisomy 21 results from nondisjunction during
meiosis in one of the parents.
• This occurrence is correlated with advanced maternal
and paternal age.
• The most common error is maternal nondisjunction in
the first meiotic division, with meiosis I errors
occurring 3 times as frequently as meiosis II errors.
• The remaining cases are paternal in origin, and
meiosis II errors predominate.

The trisomy 21 type of Down syndrome is the result of an error in meiosis, and has a
recurrence risk of about 1 in 100.
Non-disjunction in meiosis I resulting in trisomy 21 Down
syndrome
Robertsonian translocation

NORMAL CARRIER CHROMOSOME

DISORDER
• Translocation occurs when genetic material from
chromosome 21 becomes attached to another
chromosome, resulting in 46 chromosomes with 1
chromosome having extra material from
chromosome 21 attached.
• It may occur de novo or be transmitted by one of
the parents. Translocations are usually of the
centric fusion type.
• They frequently involve chromosome 14 (14/21
translocation), chromosome 21 (21/21
translocation), or chromosome 22 (22/21
translocation).
 Trisomy 21: 47,XX,+21
three separate copies of chromosome 21
• Mosaicism is considered a postzygotic event (ie, one that
occurs after fertilization).
• Most cases result from a trisomic zygote with mitotic loss
of one chromosome.

There are two different ways mosaicism can occur:

• The initial zygote had three 21st chromosomes, which
normally would result in simple trisomy 21, but during
the course of cell division one or more cell lines lost one
of the 21st chromosomes.
• The initial zygote had two 21st chromosomes, but during
the course of cell division one of the 21st chromosomes
were duplicated.