Identification of a Novel IGSF1 Variant in Two Malaysian Male Siblings with Central Hypothyroidism and Macroorchidism

What is already known on this topic?• IGSF1 mutation is the most common cause of X-linked recessive mild to moderate isolated central hypothyroidism.• It is associated with macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin and transient growth hormone deficiency What this study adds?• A novel IGSF1 c.3467T>A variant was found in 2 siblings with central hypothyroidism with macroorcidism, the first report in South East Asia.• Genetic evaluation for IGSF1 variant is important in patients with unexplained isolated central hypothyroidism +/macroorchidism to enable early detection and treatment of hypothyroidism in other similarly affected family members.