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Key Points

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  • Disease summary:

    • Down syndrome (DS) is a chromosomal aneuploidy of chromosome 21 and represents the most frequently identified cause of intellectual disability, with a wide range of severity.

    • In addition to typical facial features, the phenotype includes skeletal, neurologic, gastrointestinal, endocrine, and hematologic components or risks. Anticipatory guidance is the key to the prevention and treatment of these complications.

    • DS is associated with increased mortality in childhood (usually due to congenital heart disease) and in adulthood (due to Alzheimer disease and premature aging, among other factors).

    • Prenatal screening for DS is widely practiced and has evolved from ultrasound-based approach to combined ultrasound and biochemical marker-based approach to DNA-based approach.

  • Hereditary basis:

    • DS is usually caused by the sporadic de novo occurrence of a meiotic error involving chromosome 21 in the parent (usually the mother especially in the older age group), which is associated with a low recurrence risk.

    • A much higher recurrence risk is observed when the meiotic error is the result of a constitutional parental translocation (<5% of DS cases) or parental mosaicism (frequency unknown).

  • Differential diagnosis:

    • Single palmar (Simian) crease, sandal gap, upslanting palpebral fissures, epicanthic folds, protruding tongue, and hypotonia are seen in the majority of DS but can also be seen in normal individuals and this explains why clinical diagnosis is only accurate in two-thirds of the cases in the neonatal period. Hypothyroidism may present with similar features. Other rare disorders, such as peroxisomal disorders and Menkes syndrome are possible alternatives in infants. Short stature and mental retardation occur in a number of disorders.

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Diagnostic Criteria and Clinical Characteristics

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Diagnostic Criteria for Down Syndrome

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  • Common features

  • Epicanthic folds

  • Upslanting palpebral fissures

  • Protruding tongue

  • Single palmar creases

  • Hypotonia

  • Sandal gap (abnormally wide gap between the first and second toes)

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In one study, the above six features were identified in 100% of trisomy DS and 90% of translocation DS but in 38% of those with mosaic DS. Any of these features in isolation can be seen in normal individuals and the presence of these features combined strongly predict DS but karyotypic testing is a must to both confirm the clinical suspicion and to determine the recurrence risk (see Counseling).

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Clinical Characteristics

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The conspicuous profile of DS makes it highly unlikely that the diagnosis is first made in adulthood. A summary of the clinical features seen in adults with DS is summarized in Table 162-1. Individuals with mosaicism have variable expression of the clinical characteristics that is dependent on the proportion of trisomic cells.

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Table Graphic Jump Location
Table 162-1Clinical Characteristics of Adult Patients With DS (based on 36 adults, adapted from van Allen et al. 1999)

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