Chromosomal Abnormalities: Trisomy 21 (Down Syndrome)

Trisomy 21, also known as Down syndrome, is a condition characterized by a distinctive pattern of minor and major anomalies associated with excess chromosome 21 material.

Fig. 52. Common traits in trisomy 21 (Down syndrome)

Fig. 52. Common traits in trisomy 21 (Down syndrome)

Key findings in trisomy 21 (see Fig. 52):
Physical traits – include upslanting palpebral fissures, flat nasal bridge and midface, decreased muscle tone (hypotonia), wider space between first and second toe (“sandal gap”), nystagmus, brachycephaly, incurving of the fifth finger (clinodactyly), narrow palate, overfolded helix of the ear (especially with a small ear), short-appearing neck with redundant skin on the back of the neck, broad and short hands and feet, and single transverse crease in the palm of the hand.

Abnormal karyotype – approximately 95% of cases result from chromosomal non-disjunction of chromosome 21 (47,XX,+21 or 47,XY,+21) at conception. Translocation trisomy 21 (2% of cases) is often familial, and commonly involves chromosomes 14 and 21. Mosaicism occurs in about 2% of cases (post-zygotic non-disjunction or more rarely from trisomic rescue). In 1% of cases, the extra chromosome 21 material originates from other rearrangements.


Prenatal. Trisomy 21 may be diagnosed through direct analysis of fetal chromosomes, by karyotype or DNA microarray, obtained from amniocentesis, chorionic villus sampling, or percutaneous umbilical blood sampling. Use standard operating procedures to decide whether to accept prenatal diagnoses without postnatal confirmation (e.g. in cases of termination of pregnancy or unexamined fetal death).

Postnatal. Trisomy 21 can be strongly suspected or diagnosed clinically during the neonatal period by recognizing the typical physical traits. Clinical diagnosis should be confirmed by genetic testing (typically, karyotype from infant’s blood or tissue).

Clinical and epidemiologic notes

Major malformations associated with Down syndrome include, among others:
  • heart defects (in about 50%, most notably endocardial cushion defects)
  • gastrointestinal atresias (duodenal or esophageal atresia)
  • vertebral abnormalities.
Infants with Down syndrome can present with many other health and developmental issues, such as:
  • hypothyroidism
  • vision and hearing issues (e.g. cataracts)
  • intellectual disability of varying degree.
Additional clinical tips:
  • For diagnosis, consider physical traits with greatest discriminant diagnostic value.
  • Karyotype is needed for counselling and for estimating recurrence risk (risk in future pregnancies).
  • Look for associated anomalies, in particular, certain subtypes of heart defects, like atrioventricular canal.

Checklist for high-quality reporting

Trisomy 21 – Documentation Checklist
Describe in detail:
  • Clinical signs that allowed the diagnosis.
  • If karyotype available, report results.
  • If karyotype not available, check clinical signs on which diagnosis was based.
  • In all cases, report:
    • Associated malformations.
    • Specialty consultations (including genetic and cardiology) and the results, if applicable.
    • Take and report photographs: Show clearly the side and front views of the face; can be crucial for review.
    • Describe evaluations to find or rule out related and associated anomalies.
      • General – hypotonia.
      • Head and neck – brachycephaly, large anterior fontanelle, short neck, excess nuchal skin, protruding tongue, narrow palate, flat nasal bridge, upslanting palpebral fissures, epicanthal folds, nystagmus, Brushfield spots on iris, small ears (<3 cm), overfolded helix (ear).
      • Chest – absent breast buds.
      • Extremities – short broad hands, fifth finger clinodactyly, fifth finger single flexion crease, single palmar crease, wide gap between first and second toe.
    • Document specialty consultations (e.g. genetics, cardiology).
    • Report whether autopsy (pathology) findings are available and if so, report the results.