What are the typical clinical characteristics of a patient with trisomy 21 (Down syndrome)?

Clinical Characteristics of Trisomy 21 (Down Syndrome)

Trisomy 21 presents with a characteristic constellation of physical features including hypotonia, distinctive craniofacial dysmorphology, congenital heart defects in 40-73% of cases, and moderate to severe intellectual disability. 1, 2

Craniofacial and Physical Features

Virtually all individuals with Down syndrome are hypotonic and display minor dysmorphic features that create a recognizable facial appearance 1, 3:

• Upslanting palpebral fissures 1
• Epicanthal folds 1
• Flat nasal bridge 1, 4
• Brushfield spots of the iris 1
• Shortened, incurving fifth finger (clinodactyly) 1
• Transverse palmar crease (single palmar crease) 1
• False macroglossia (tongue appears large relative to small oral cavity), muscular hypotonia, and gothic (high-arched) palate 4

These craniofacial features are quantitatively distinct from euploid individuals, though faces of children with DS show only slightly increased variation with most falling within the range established by unrelated controls 5.

Cardiac Abnormalities

Congenital heart disease occurs in 40-73% of individuals with Down syndrome, making cardiac screening essential in all cases 1, 2:

• Atrioventricular septal defect (AVSD) is the hallmark cardiac anomaly, occurring in approximately 15-30% of affected individuals, with more than 75% of complete AVSDs occurring in patients with Down syndrome 2
• Type 3 (Inlet) ventricular septal defects are particularly associated with trisomy 21 2
• Tetralogy of Fallot, patent ductus arteriosus, atrial septal defect, and ventricular septal defect are also common 1

Early echocardiographic evaluation is mandatory for all infants diagnosed with trisomy 21, regardless of clinical symptoms 2.

Gastrointestinal and Other Organ System Involvement

• Gastrointestinal anomalies occur in 5% of cases, including duodenal atresia and Hirschsprung disease 1
• Short stature is a consistent feature 1, 4

Hematologic and Oncologic Features

The incidence of childhood leukemia is increased up to 20 times over the general population 1:

• Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are both significantly increased 1
• Leukemia predisposition is inherent to the trisomy 21 state 1

Neurodevelopmental Profile

Down syndrome is one of the most common genetic causes of moderate to severe intellectual disability 1:

• Median IQ is approximately 50 1
• Developmental delays are recognized in infancy and persist throughout life 1
• Adults with Down syndrome experience neuronal degeneration identical to Alzheimer disease, with universal occurrence of Alzheimer histopathology and high prevalence of dementia 6

Multisystem Involvement

The syndrome affects multiple organ systems simultaneously 1:

• Immunodeficiency contributes to increased infection risk 4
• Temporomandibular joint dysfunction and malocclusion are common 4
• Retarded psychomotor development complicates treatment and daily functioning 4

Critical Clinical Pitfalls

Do not rely on clinical features alone for diagnosis—chromosomal verification through karyotyping is required to definitively diagnose Down syndrome and identify the specific chromosomal pattern (free trisomy 21, Robertsonian translocation, or reciprocal translocation) 3.

Patients with Down syndrome and AVSD are at particular risk for developing pulmonary arterial hypertension and require careful monitoring, as complete AVSD requires surgical repair typically before 6 months of age to prevent irreversible pulmonary vascular disease 2.

Genetic evaluation is recommended for all patients with congenital heart disease accompanied by extracardiac malformations or neurodevelopmental abnormalities to identify trisomy 21 and other genetic syndromes 1.