DYRK1A Expression and Thyroid Dysfunction in Subjects With Down Syndrome

Thyroid dysfunction is common in Down Syndrome (DS). The age of onset and etiology is largely unexplored. Murine models suggest role of DYRK1A gene in thyroid dysgenesis in DS. DYRK1A overexpression is associated with immune dysfunction and autoimmune diseases in DS. In this study, we aimed to determine the expression of the DYRK1A gene in relation to age of onset and autoimmune status in individuals with DS who have hypothyroidism.

This cross-sectional study was conducted in a tertiary care setting and included five groups: individuals with DS and hypothyroidism, DS with euthyroidism, congenital hypothyroidism without DS, autoimmune hypothyroidism without DS, and age-matched healthy controls without thyroid dysfunction. History, clinical details such as age of onset, thyroid function tests including antibodies, and DYRK1A expression were assessed.

Of the 72 DS included, 24 were euthyroid. 48 (66.7%) had primary hypothyroidism and 28 (58.3%) of those were anti-TPO negative. Hypothyroidism was detected in 20 patients with DS below 1 year of age who were all anti-TPO-negative. The remaining 28 with DS with hypothyroidism developed disease after 3 years of age of whom 20 (71.4%) were anti-TPO positive. DS with hypothyroidism had higher expression (6.33-fold) of DYRK1A compared to euthyroid DS (p < 0.0001). DYRK1A expression was 5.17-fold and 7.27-fold higher in anti-TPO-positive and anti-TPO-negative respectively compared to healthy population (p < 0.0001). Individuals with DS without hypothyroidism, congenital hypothyroidism (without DS), autoimmune hypothyroidism (without DS) had DYRK1A expression of 1.36, 0.68, and 0.82-fold compared to healthy.

DYRK1A expression is overexpressed in individuals with Down syndrome with hypothyroidism, encompassing both early-onset non-autoimmune and later-onset autoimmune forms.