IGSF1 and Central hypothyroidism: In keeping with previous reports, biochemical penetrance of thyroid dysfunction in the L773P kindred was variable, although all hemizygous males had mild or moderate central hypothyroidism according to ESPE criteria.29 Ascertainment following identification of an IGSF1 mutation may precipitate diagnosis of moderate central hypothyroidism in apparently asymptomatic individuals, whereas other subjects with comparable biochemistry present symptomatically, suggesting variable physiological penetrance.4 Consistent with this, Case 1a had the lowest FT4 concentrations (6.9 pmol/L).