Down Syndrome (Trisomy 21)
What is Down Syndrome?
A drawing of the facial features of a child with Down syndrome.
● It is primarily caused by trisomy of
chromosome 21, which gives rise to multiple systemic
complications as part of the syndrome.
● Langdon Down first described the condition
in 1866, but its cause was a mystery for many years.
● In 1932, it was suggested that a
chromosomal anomaly might be the cause, but the
anomaly was not demonstrated until 1959.
Pathophysiology
Two different hypotheses have been proposed to explain the mechanism of gene action in Down
syndrome: developmental instability (ie, loss of chromosomal balance) and the so-called
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.
● Molecular analysis reveals that the 21q22.1-q22.3 region, also known as the Down
syndrome critical region (DSCR), appears to contain the gene or genes responsible
for the congenital heart disease observed in Down syndrome.
● Abnormal physiologic functioning affects thyroid metabolism and intestinal
malabsorption; patients with trisomy 21 have an increased risk of obesity; frequent
infections are presumably due to impaired immune responses, and the incidence of
autoimmunity, including hypothyroidism and rare Hashimoto thyroiditis, is increased.
● Patients with Down syndrome have decreased buffering of physiologic reactions,
resulting in hypersensitivity to pilocarpine and abnormal responses on
sensory-evoked electroencephalographic (EEG) tracings.
● Decreased buffering of metabolic processes results in a predisposition to
hyperuricemia and increased insulin resistance.
● Children with Down syndrome are predisposed to developing leukemia, particularly
transient myeloproliferative disorder and acute megakaryocytic leukemia.
● Musculoskeletal manifestations in patients with Down syndrome include reduced
height, atlanto occipital and atlantoaxial hypermobility, and vertebral malformations of
the cervical spine.
● About 5% of patients with Down syndrome have GI manifestations, including
duodenal atresia, Hirschsprung disease, and celiac disease.
, Statistics and Incidences
Down syndrome have been observed in nearly all countries and races.
Facial features of a baby with Down Syndrome.
● Each year, approximately 6000 children are born with Down syndrome.
● Down syndrome accounts for about one-third of all moderate and severe mental
handicaps in school-aged children.
● The prevalence of Down syndrome worldwide has increased because of increases in
lifespan in the last few decades.
● The characteristic morphologic features will be obvious in children older than 1 year.
● On rare occasions, the disease can be observed in a few members of a family; the
risk for recurrence of Down syndrome in a patient’s siblings also depends on
maternal age.
● The male-to-female ratio is slightly higher (approximately 1.15:1) in newborns with
Down syndrome, but this effect is restricted to neonates with free trisomy 21.
● Perhaps 50% of female patients with trisomy 21 are fertile, and these females have
up to a 50% chance of having a live child who also has trisomy 21.
Causes
The cause of DS is not known, although several theories dominate.
What is Down Syndrome?
A drawing of the facial features of a child with Down syndrome.
● It is primarily caused by trisomy of
chromosome 21, which gives rise to multiple systemic
complications as part of the syndrome.
● Langdon Down first described the condition
in 1866, but its cause was a mystery for many years.
● In 1932, it was suggested that a
chromosomal anomaly might be the cause, but the
anomaly was not demonstrated until 1959.
Pathophysiology
Two different hypotheses have been proposed to explain the mechanism of gene action in Down
syndrome: developmental instability (ie, loss of chromosomal balance) and the so-called
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.
● Molecular analysis reveals that the 21q22.1-q22.3 region, also known as the Down
syndrome critical region (DSCR), appears to contain the gene or genes responsible
for the congenital heart disease observed in Down syndrome.
● Abnormal physiologic functioning affects thyroid metabolism and intestinal
malabsorption; patients with trisomy 21 have an increased risk of obesity; frequent
infections are presumably due to impaired immune responses, and the incidence of
autoimmunity, including hypothyroidism and rare Hashimoto thyroiditis, is increased.
● Patients with Down syndrome have decreased buffering of physiologic reactions,
resulting in hypersensitivity to pilocarpine and abnormal responses on
sensory-evoked electroencephalographic (EEG) tracings.
● Decreased buffering of metabolic processes results in a predisposition to
hyperuricemia and increased insulin resistance.
● Children with Down syndrome are predisposed to developing leukemia, particularly
transient myeloproliferative disorder and acute megakaryocytic leukemia.
● Musculoskeletal manifestations in patients with Down syndrome include reduced
height, atlanto occipital and atlantoaxial hypermobility, and vertebral malformations of
the cervical spine.
● About 5% of patients with Down syndrome have GI manifestations, including
duodenal atresia, Hirschsprung disease, and celiac disease.
, Statistics and Incidences
Down syndrome have been observed in nearly all countries and races.
Facial features of a baby with Down Syndrome.
● Each year, approximately 6000 children are born with Down syndrome.
● Down syndrome accounts for about one-third of all moderate and severe mental
handicaps in school-aged children.
● The prevalence of Down syndrome worldwide has increased because of increases in
lifespan in the last few decades.
● The characteristic morphologic features will be obvious in children older than 1 year.
● On rare occasions, the disease can be observed in a few members of a family; the
risk for recurrence of Down syndrome in a patient’s siblings also depends on
maternal age.
● The male-to-female ratio is slightly higher (approximately 1.15:1) in newborns with
Down syndrome, but this effect is restricted to neonates with free trisomy 21.
● Perhaps 50% of female patients with trisomy 21 are fertile, and these females have
up to a 50% chance of having a live child who also has trisomy 21.
Causes
The cause of DS is not known, although several theories dominate.
