Trisomy 21 (Down)

A happy 8-year old boy with Down's syndrome.



Down syndrome, or Trisomy 21, is a genetic syndrome caused by a triplication of chromosome 21. It occurs in about 1/800 to 1/1000 live births. Down syndrome is thus one of the most common genetic syndromes and the number one genetic cause of intellectual disability.


95% of the time, Down syndrome is caused by sporadic (not inherited) maternal non-disjunction of chromosome 21; 4% of the time, it is due to an unbalanced translocation between chromosome 21 and, usually, chromosome 14, a process known as Robertsonian translocation; 1% of the time, mosaicism is present, where both a normal cell line and a cell line with trisomy 21 are present.

Karyotype for trisomy Down syndrome: notice the three copies of chromosome 21

Risk Factors

  1. Advance maternal age
  2. Previous child with Trisomy 21 (1% above baseline risk)



Physical characteristics that are common in persons with Down syndrome, and that should raise suspicion in the neonate are:

  1. Hypotonia
  2. Upward slanting palpebral fissures
  3. Brachycephaly- flat occiput
  4. Clinodactly with short 5th finger
  5. Protruding tongue
  6. Flat nasal bridge
  7. Epicanthal folds
  8. Brushfield spots (spots on iris)
  9. Ear abnormalities (low set ears, stenotic meatus)
  10. Single palmar crease
  11. Congenital cardiac defect (VSD, AV canal defects)
  12. Duodenal atresia
  13. intellectual disability (mean IQ of 50)
  14. Loose nuccal skin
  15. Short Fingers
  16. Hirschsprung’s Disease
  17. Space between 1st and 2nd digits of feet (sandal deformity)

Feet of a boy with Down syndrome, showing the deviated first toes

Brushfield spots, visible in the irises of a baby with Down syndrome



Pre-natal diagnosis of Down syndrome is suspected with an abnormal triple screen test (low AFP, low estriol and high b-HCG). A definitive diagnosis is made with a karyotye of fetal cells, done by chorionic villus sampling between 9 and 11 weeks, by amniocentesis, between 16 to 18 weeks, or now by non-invasive free floating fetal DNA, as early as 10 weeks1.

Post-natal diagnosis can be made when an infant presents with signs or physical characteristics of Down syndrome. A karyotype analysis will reveal the triplicate material of chromosome 21. It may be advisable to refer parents to a geneticist at this time, to evaluate future risk of recurrence based on maternal age and karyotype.


Complications and Treatment

In the care of children with Down syndrome, it is important to note that there are certain complications and risks that are higher in these patients than in the average population. Therefore, anticipatory guidance is essential. Certain medical complications that occur in-patients with Down syndrome include:

  1. Congenital cardiac defects — these can occur in 40 to 60% of patients with Down’s syndrome, and include complete AV canal defects, VSD and tetralogy of Fallot. Because of this risk, ALL newborns with Down syndrome should have an echocardiogram and ECG to screen for heart defects. If found, the patient should be referred to a pediatric cardiologist.
  2. Ear, nose and throat defects — Children with Down syndrome may have ear abnormalities that can predispose to serous otitis media, pharyngitis and sinusitis. Infections should be treated aggressively, and hearing should be evaluated at 6 months of age. Because of floppy airways, increase incidence of obstructive sleep apnea.
  3. Orthopedic issues - Alanto-axial or alanto-occipital instability, scoliosis and foot deformities are common orthopedic problems in children with Down syndrome. This may necessitate referral to a specialist if problems are discovered. The American Academy of Pediatrics recommends that children with Down syndrome should have screening radiographs at 3-5 years of age to look for alantoaxial instability, particularly if they are involved in contact sports.
  4. Gastrointestinal defects - newborns with feeding or stooling problems should be suspected of having some type of GI defect. Common GI issues in patients with Down syndrome include: duodenal atresia, esophageal atresia, tracheoesophageal fistula, and imperforate anus. An upper GI series or barium enema may be necessary to rule out a GI malformation. There is also a high rate of Hirschsprung's disease.
  5. Developmental deficits - children with Down syndrome have decreased cognitive function, but this varies (low normal intelligence to profound intellectual disability) and is impossible to predict at birth. The physician should evaluate development at each visit, and referral should be made as early as possible to early intervention programs, as appropriate therapy can help to minimize developmental delay.
  6. Other issues: These are numerous and can include: cataracts, lukemeoid reactions, seizures, dental problems, skin dryness and thyroid disease.


Because of the various health supervision requirements, it is important for medical professionals caring for infants, children and teens with Down Syndrome to be familiar with the Table in Appendix 1 of American Academy of Pediatrics Health Supervision Guidelines for Children with Down Syndrome.



A boy with Down syndrome using a cordless drill to assemble a book case

Support for families can be invaluable when facing a pre or post-natal diagnosis of trisomy 21.  Enlist the help of a social worker within the genetics department for additional resources, but here are some parent-run support organizations that can be helpful for families.


National Association for Down Syndrome - variety of resources including a section on "New Parents", Teens & Adults, and Grandparent support.  Website also available in Spanish & with links to local resources & groups.


National Down Syndrome Society - large resource including information on early intervention, therapy, behavior, education and
local & national advocacy information.



  1. Bull, MJ, et al. Clinical Report:  Health Supervision for Children with Down Syndrome. Pediatrics. 2011. 128(2):393-406
  2. American Academy of Pediatrics. Health Supervision for Children with Down Syndrome. Pediatrics. Vol 107. No. 2 2001, pp. 855-859.
  3. Sanez, R. Primary Care of Infants and Young Children with Down Syndrome. American Family Physician. Vol 59, No. 2, 1999: pp. 329-395.
  4. Scioscia, A., Jones, K. Responding to Parental Concerns After a Prenatal Diagnosis of Trisomy 21. Pediatrics. Vol. 107. No. 4, 2001: pp. 204-208.
  5. Simpson J. Choosing the Best Prental Screening Protocol.  NEJM Nov 10, 2005
  6. Newberger, D. Down Syndrome: Prenatal Risk Assessment and Diagnosis. American Family Physician 2000 August 15; 62(4): 825-832.