Select Characteristics
- Flattened face
- Upslanting palpebral fissures
- Epicanthal folds
- Short neck
- Brushfield spots
- Low-set, folded ears
Genetics
- Trisomy 21 (meiotic nondisjunction)
- Each cell has 3 copies (instead of 2) of chromosome 21, which is called aneuploidy.
- Trisomy 21 is responsible for ~ 95% of cases of Down syndrome.
- The risk of trisomy 21 increases with advanced maternal age:
- Translocation Down syndrome (unbalanced translocation)
- 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
- Mosaic 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.
- Mosaicism is responsible for ~ 1% of cases of Down syndrome.
Typical dysmorphic features and other clinical characteristics
- Flattened face, especially at the nasal bridge
- Upslanting palpebral fissures (ie, eyes appear to slant upward)
- Epicanthal folds
- Upper eyelid skin fold covers the inner corner of the eye.
- Short neck with excessive skin at the back (the nape)
- Brushfield spots
- 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).
- Low-set, small, folded ears
- Brachycephaly
- Bilateral coronal suture fusion leads to a skull that is shorter and wider than normal.
- Extremity abnormalities
- Single transverse palmar (aka Simian) crease
- "Sandal gap": gap between the 1st and 2nd toes
Medical comorbidities
- Duodenal atresia and Hirschsprung disease
- Congenital heart disease
- Atrioventricular septal defect is the most common defect but others exist
- Leukemia
- ALL and AML
- Obstructive sleep apnea
Delay of Motor Milestones
- Average walking age of 26 months.
- Diffuse hypotonia
Cognitive and Psychiatric Impairment
- Mild to moderate intellectual disability
- Alzheimer disease
- Chromosome 21 codes for amyloid precursor protein
- Autism
- Disruptive behavioral disorders
Diagnosis
- Often made with prenatal testing.
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.
- Roizen NJ, Patterson D. Down's syndrome. Lancet 2003; 361:1281.
Image References
- Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental, 2012 (Background image of the child with Down syndrome)
- Work from Symon Tomczak, 2012 (the Brushfield spot)
- Work from Sarang, 2009 (Epicanthal fold)