Down Syndrome

Genetics

Each cell has 3 copies (instead of 2) of chromosome 21, which is called aneuploidy.

Aneuploidy refers to an extra or reduced number of chromosomes: in this case, there is an extra chromosome 21.

1:1500 cases in women < 20 years old vs. 1:25 cases in women > 45 years old

Secondary to a Robertsonian translocation between chromosomes 14 and 21.
In translocation, there is an exchange of chromosomal material between two chromosomes (in this instance, chromosomes 14 and 21). When the translocation is balanced, there's no overall loss or gain of chromosomal material present. For instance, a carrier of translocation Down syndrome has just 45 chromosomes (rather than 46) but has the normal amount of genetic material, overall, because one copy of chromosome 21 has translocated to chromosome 14 (which makes up for the loss). When it's unbalanced, there is either too much or too little overall amount of chromosomal material present; the clinical effect depends on the type of translocation.
When extra chromosome 21 material is present, the clinical effect is Down syndrome, because, just like in trisomy 21, there are 3 copies of chromosome 21.
Translocation is responsible for ~ 4% of cases of Down syndrome

Mosaicism refers to the presence of aneuploidy in some of the cells but not all of them.
It can occur in two different ways that involve nondisjunction at either the meiotic and mitotic steps in certain cells.

The result is that some (but not all) of the cells have trisomy 21.

Typical dysmorphic features and other clinical characteristics

Small, typically white-colored, slightly elevated spots, arranged in a ring (circumferentially), at the periphery of the iris (as opposed to the Lisch nodules of NF 1, which are yellow-brown hamartomas).

Bilateral coronal suture fusion leads to a skull that is shorter and wider than normal.

Medical comorbidities

Delay of Motor Milestones

Cognitive and Psychiatric Impairment

Diagnosis

REFERENCES

Breslin J, Spanò G, Bootzin R, et al. Obstructive sleep apnea syndrome and cognition in Down syndrome. Dev Med Child Neurol 2014; 56:657.

Epstein CJ. Down syndrome (Trisomy 21). In: The metabolic and molecular bases of inherited disease, 8th ed, Scriver CR, Beaudet AL, Sly WS, Valle D (Eds), McGraw-Hill, New York 2001. p.1223.

Jones KL. Down syndrome. In: Smith's recognizable patterns of human malformation, 6th ed, Elsevier Saunders, Philadelphia 2006. p.7

McDowell KM, Craven DI. Pulmonary complications of Down syndrome during childhood. J Pediatr 2011; 158:319.

Roizen NJ, Amarose AP. Hematologic abnormalities in children with Down syndrome. Am J Med Genet 1993; 46:510.

Image References

Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental, 2012 (Background image of the child with Down syndrome)