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MON-270 Diagnostic Exome Sequencing in Children with Permanent Congenital Hypothyroidism

Abstract Introduction: Congenital hypothyroidism can be caused by aplasia or hypoplasia of the thyroid gland, ectopic thyroid, or dyshormonogenesis. Thyroid function test, thyroid ultrasonography, and thyroid scintigraphy may be helpful in diagnosis. Molecular genetic approach can be used to identify the genetic causes. In this study, diagnostic exome sequencing (DES) including 23 genes associated with congenital hypothyroidism was performed to identify the genetic causes of congenital hypothyroidism. Methods: The patients who were diagnosed as permanent congenital hypothyroidism and agreed to the genetic test were included in the study. We reviewed the clinical information, laboratory tests, and imaging findings based on medical records, retrospectively. Genetic test was performed with an informed consent. Results: A total of 26 children were included in the study. Twelve (46%) were boys and 14 (54%) were girls (M:F 1:1.16). Morphologically, there were 1 (3%) hypoplasia and 1 (3%) agenesis. Twelve (46%) showed ectopic thyroid, and 12 (46%) had normally positioned thyroid. Eighteen (69%) patients were diagnosed within one month of age, and 8 (31%) were diagnosed after one month later. Initial thyroid function test revealed 112.68±55 ng/dL of T3, 0.71±0 ng/dL of fT4, and 77.26±112uIU/mL of TSH. Eighteen (69%) showed overt hypothyroidism and 8 (31%) patients were in subclinical hypothyroidism. On recent follow-up, the mean age was 10.85 years. All of them are taking levothyroxine and the mean levothyroxine dose is 2.15ug/kg/day. In four (15%) patients, pathogenic mutations were found. There were heterozygous mutations of the gene TSHR in 2 patients, compound heterozygous mutation of TG gene in 1 patient, and compound heterozygous mutation of DUOX2 gene in 1 patient. In addition, fifteen (57%) patients showed several VUS (variants of uncertain significance) in at least one of TRH, TRHR, TSHR, SLC26A4, PAX8, TG, TPO, DUOX2, DUOXA2, and POU1F1 genes by DES. Conclusion: We could find pathogenic mutations in 4 patients (15%) among 26 patients with permanent congenital hypothyroidism by DES.