Diagnostic algorithm of Down syndrome by minor physical anomaly

Area of Science:

• Medical Genetics
• Clinical Diagnostics
• Human Development

Background:

• Down syndrome (DS) is the most common cause of intellectual disability, typically diagnosed via karyotyping.
• Karyotyping's high cost can delay crucial early interventions for individuals with DS and their families.
• Minor physical anomalies (MPAs) are in-utero developmental insults present from early embryonic development, persisting throughout life.

Purpose of the Study:

• To investigate the diagnostic utility of minor physical anomalies (MPAs) in identifying Down syndrome (DS).
• To explore demographic factors associated with DS diagnosis.
• To develop a more accessible diagnostic approach for DS.

Main Methods:

• A study involving 70 karyotyped DS cases, 70 with other intellectual disabilities (Other ID), and 70 controls (Average).
• Application of the Modified Waldrop’s scale (Ismail's 41-item scale) to assess MPAs.
• Demographic analysis and decision tree algorithms using SPSS v.25.

Main Results:

• Paternal and maternal age at childbirth, maternal age at marriage, and income were significant factors in DS.
• The DS group exhibited significantly more MPAs (mean=17.04) compared to Other ID (mean=5.93) and Average (mean=1.59) groups.
• Big sandal gap, high-arched palate, and epicanthus were the most frequent MPAs in DS. Combinations like clinodactyly/high-arched palate or epicanthus/telecanthus achieved high diagnostic sensitivity (0.945) and negative predictive value (0.979).

Conclusions:

• Certain MPAs, including epicanthus, telecanthus, high-arched palate, and curved fifth finger, are key differentiating features for DS.
• The simian crease, often cited, is not specific for DS.
• These findings suggest a promising avenue for developing cost-effective DS screening tools, though larger studies are needed.