ESPE Abstracts

Aim: To describe the phenotypes of patients harboring bi-allelic pathogenic variants in IYD gene followed in our Paediatric Endocrinology Clinic.

Results: Eight patients (from 4 consanguineous families of Moroccan origin) were homozygous carriers for a pathogenic variant in IYD gene. Their clinical presentation is described in table. All patients presented with a large goiter and severe hypothyroidism with very high thyroglobulin (Tg) plasma level. The goiter subsided with L-thyroxine therapy and iodine supplements. Treatment could be interrupted in 5 patients, while for the 3 others, goiter and hypothyroidism reappeared so that treatment was resumed. Affected individuals in families 2, 3, 4 harbor the same known pathogenic variant (c.658G>A, p.(Ala220Thr) NM_001164694.1) while 3 affected individuals from family 1 harbor a novel missense mutation (c.791C>T, p.(Pro264Leu) NM_203395) considered likely pathogenic based on segregation, correlation with phenotype, and high pathogenicity scores (no genetic analysis for patient 1d). No heterozygous carrier had a thyroid disease history.

Conclusion: Hypothyroidism due to bi-allelic pathogenic variants in IYD gene is characterized by a large goiter, very high thyroglobulin levels and fluctuating thyroid function. No patient was diagnosed in the neonatal period and a majority of patients could be weaned from L-thyroxine after an episode of profound goitrous hypothyroidism. We didn’t observed any phenotype–genotype correlation with a wide phenotypic variability within families. We report a novel IYD variant in a consanguineous family with 4 affected individuals.