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Discordance of Monozygotic Twins for Thyroid Dysgenesis: Implications for Screening and for Molecular Pathophysiology

Department of Pediatrics, University of Montréal (R.P., G.V.V.), Montréal, Québec, Canada H3T 1C5; Department of Pediatrics (C.H., P.B.), and Interdisciplinary Research Institute and Department of Medical Genetics (G.V.), Free University of Brussels, 1070 Brussels, Belgium; Department of Pediatrics, University of Sherbrooke (K.K.), Sherbrooke, Québec, Canada J1H 5N4; and Departments of Medicine and Pediatrics, Laval University (F.S., J.H.D.), Québec City, Québec, Canada G1V 4G2

Address all correspondence and requests for reprints to: Dr. Guy Van Vliet, Endocrinology Service, Sainte Justine Hospital, 3175 Sainte Catherine Road, Montréal, Québec, Canada H3T 1C5. E-mail: . gvanvliet{at}justine.umontreal.ca

Abstract

Since the advent of biochemical screening for congenital hypothyroidism, the majority of monozygotic twins reported with thyroid dysgenesis have been discordant, and most were missed on neonatal screening, presumably due to fetal blood mixing. We hypothesized that there may be bias leading to preferential reporting of discordant twins and/or of false negative screening results. Therefore, we performed a systematic search for twins in two congenital hypothyroidism screening centers, Quebec and Brussels, that use a primary TSH approach.

In Quebec, 10 pairs of twins were identified, all discordant for congenital hypothyroidism due to thyroid dysgenesis (4 monozygotic and 4 dizygotic pairs) and dyshormonogenesis (2 dizygotic pairs). The 6 pairs identified in the Brussels database were also all discordant for congenital hypothyroidism due to thyroid dysgenesis (1 monozygotic and 3 dizygotic pairs) and dyshormonogenesis (2 dizygotic pairs). The median increase in TSH between screening and diagnosis was 7-fold in the monozygotic twins vs. 2-fold in matched singletons (P = 0.02), suggesting fetal blood mixing between the twins.

In summary, discordance for thyroid dysgenesis is the rule in monozygotic twins, and fetal blood mixing may result in delayed or missed diagnoses. We therefore conclude that 1) a second sample for congenital hypothyroidism screening at 14 d of age should be considered for all same-sex twins; and 2) thyroid dysgenesis generally results from epigenetic phenomena, early somatic mutations, or postzygotic stochastic events.

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