Novel variants in the SOX11 gene: additional evidence for the involvement of SOX11 in hypogonadotropic hypogonadism

Abstract Pathogenic SOX11 variants have been associated with intellectual developmental disorder with microcephaly, and with or without ocular malformations or hypogonadotropic hypogonadism (IDDMOH, OMIM # 615866). In this article, we report seven new patients with SOX11 variants, five of whom have features suggestive of hypogonadotropic hypogonadism (HH). The main clinical features included neurodevelopmental delay (7/7) and intellectual disability (5/7), autism/attention deficit hyperactivity disorder (5/7), microcephaly (4/7), short stature (4/7), hypotonia (4/7), and clinodactyly of the 5th fingers (5/7). HH was confirmed in two female patients with primary amenorrhea, nonvisualized/prepubertal size of the uterus, and nonvisualized ovaries. Two of the male patients presented with micropenis, two had cryptorchidism, and one had decreased testicular size. These findings are suggestive of HH and appear to be more common than previously described among individuals with pathogenic SOX11 variants. Therefore, SOX11 should be included in diagnostic gene panels for patients with hypogonadotropic hypogonadism.