Wide Spectrum of Deficiency: From Life-Threatening Compressive Goiter in Infancy to Lifelong Euthyroidism.

Six patients are described with bi-allelic variants and widely variable phenotypes. Patient 1 is an infant with a compressive hypothyroid goiter causing respiratory distress, which was promptly alleviated by levothyroxine (LT4). He was a compound heterozygote for variants, including a novel deletion of 540 base pairs. Patients 2 and 3 are siblings with the same compound heterozygous mutations of , yet one had overt hypothyroidism at 14 months and the other lifelong euthyroidism. Patient 4 is a compound heterozygote individual and has mild persistent congenital hypothyroidism; his sister (patient 5) only had a borderline thyrotropin elevation at newborn screening, consistent with homozygous variants with a mild impact on enzyme activity. Their euthyroid mother (patient 6) is a compound heterozygote for the same mutations as her son. Targeted exome sequencing did not reveal any relevant modifiers. It is concluded that (i) prompt LT4 replacement in infants with respiratory distress due to a hypothyroid goiter makes surgery unnecessary; and (ii) the clinical expression of DUOX2 deficiency varies widely between individuals and over time, justifying periodic reevaluation of the need for LT4 replacement.