Down syndrome

Phenotype across life stages

Prenatal

• Increased nuchal translucency
• Absent or hypoplastic nasal bone
• Duodenal atresia (double bubble sign)
• Congenital heart disease, classically atrioventricular septal defect

Neonatal

Physical findings

• Hypotonia
• Flat facial profile
• Brachycephaly
• Upslanting palpebral fissures
• Depressed nasal bridge
• Protruding tongue
• Excess nuchal skin
• Single transverse palmar crease
• Sandal gap between first and second toes
• Generalised ligamentous laxity

Radiological findings

• Proximal bowel obstruction pattern
  • Duodenal atresia
  • Annular pancreas
• Hisrchprung-type distal bowel obstruction pattern
• Cardiomegaly / pulmonary plethora if significant shunt lesion

Childhood

Physical findings

• Persistent short stature
• Developmental delay
• Characteristic facial appearance: same as neonatal period plus epicanthic folds and small ears
• Relative macroglossia

Clinical issues

• Recurrent ENT and respiratory infections
• Hearing impairment
• Visual problems, including cataracts and strabismus
• Increased risk of obstructive sleep apnoea (due to adenotonsillar hypertrophy + relative macroglossia)
• Endocrine/immune associations such as hypothyroidism and coeliac disease

Radiological findings

• Atlantoaxial instability: increased atlantodental interval
  • ± atlanto-occipital instability
• Delayed skeletal maturation
• Hip instability

Adult

Physical findings

• Premature ageing appearance
• Obesity

Clinical issues

• OSA
• Early-onset dementia, especially Alzheimer
• Cervical myelopathy from atlantoaxial instability

Trivia

• Even though trisomy 21 is chromosomal basis in most cases, not every patient with Down syndrome has full extra copy of chromosome 21, other main genetic mechanisms are:
  • Robertsonian translocation involving chromosome 21
  • Mosaic trisomy 21