Genetic testing may help confirm diagnosis for children with congenital hypothyroidism
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Key takeaways:
- Genetic testing led to a change in diagnosis for 10 of 48 children with congenital hypothyroidism.
- The change in diagnosis allowed seven participants to be trialed off levothyroxine therapy.
Genetic testing can be used to confirm a congenital hypothyroidism diagnosis for children, according to findings published in the European Thyroid Journal.
“Genetic testing can change diagnosis and treatment decisions in a small proportion of children with congenital hypothyroidism, but the resulting benefit may outweigh the burden of lifelong follow-up and treatment,” Cengiz Kara, MD, PhD, professor in the department of pediatric endocrinology, faculty of medicine at Istinye University in Istanbul, and colleagues wrote.
Researchers recruited 48 children diagnosed with primary congenital hypothyroidism shortly after birth who attended a follow-up examination from April to September 2017 (48.5% boys). Congenital hypothyroidism diagnoses were based on a national newborn screening program. Participants were divided into three diagnostic groups: permanent congenital hypothyroidism, transient congenital hypothyroidism and persistent hyperthyrotropinemia. Classification took place at presentation, during follow-up or during a reevaluation at age 2 to 3 years. Genetic analysis was conducted to reclassify all participants. Genotype-phenotype correlations were assessed, with participants defined as solved if there was a decisive link between the genotype and phenotype. Children whose genetic variants contributed to the phenotype but had a weaker causal link than the solved group were classified as ambiguous. Participants with no pathogenic variant in the targeted genes were considered to be unsolved, the researchers wrote.
Before genetic testing, 26 participants had permanent congenital hypothyroidism, 15 had transient congenital hypothyroidism and seven had persistent hyperthyrotropinemia. After genetic testing, 10 children had a change in diagnostic category, with 21 children in the permanent congenital hypothyroidism group, 23 in the transient congenital hypothyroidism group and four with persistent hyperthyrotropinemia. Seven children initially diagnosed with permanent congenital hypothyroidism began a trial off medication because of the presence of monoallelic DUOX2, TG or TSHR variants, or the absence of a pathogenic variant, according to the study.
“The targeted 23-gene high-throughput sequencing panel yielded a definitive molecular diagnosis in 57% of permanent congenital hypothyroidism patients with gland in situ,” the researchers wrote. “However, genetic origin of transient congenital hypothyroidism was found to be relatively low, suggesting that environmental factors may have a predominant role in the etiopathogenesis of transient congenital hypothyroidism.”
Of the cohort, 46% were considered to be solved after genetic testing and 19% were ambiguous, with 41 genetic variants detected. The genes most affected by variants were the TG, TSHR and DUOX2 genes. The remaining 35% of the cohort were unsolved with no pathogenic variant identified.
“These data need to be confirmed in larger patient groups,” the researchers wrote. “Also, in vitro functional studies are required to verify pathogenicity of novel variants described for the first time in this study.”
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