Journal Article

Neonatal Screening for Congenital Hypothyroidism: What Can We Learn From Discordant Twins?

Gelsomino, Rossella, Olivieri, Antonella, de Filippis, Tiziana, Caiulo, Silvana, De Angelis, Simona, Weber, Giovanna, Costa, Pietro, Bartolucci, Monica, Di Frenna, Marianna, Gabbianelli, Marco, Persani, Luca, Rotondi, Daniela, Calaciura, Francesca, Cassio, Alessandra, Ortolano, Rita, Medda, Emanuela, Vigone, Maria Cristina, Gelmini, Giulia

2019

Overview

Newborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates. To estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH. Forty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH. Seven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors. This study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.

• Publisher: Copyright Oxford University Press,Oxford University Press
• Subject: Analysis / Congenital diseases / Diagnosis / Environmental factors / Etiology / Fetuses / Genetic disorders / Genetic factors / Hypothyroidism / Infants (Newborn) / Liability (Law) / Medical screening / Neonates / Phenotypic variations / Thyroid / Thyroid hormones / Thyroid-stimulating hormone / Twins