<i>SOX2</i> Variant Resulting in Hypogonadotropic Hypogonadism, Learning Difficulties, and Ear (Rather Than Eye) Anomalies

A 15-year-old female individual presented with primary amenorrhea and absence of pubertal signs. Her hormonal profile revealed isolated hypogonadotropic hypogonadism (IHH) with low levels of luteinizing hormone (LH), estradiol, and follicle-stimulating hormone (FSH), with a confirmatory luteinizing hormone-releasing hormone (LHRH) stimulation test. She has a background of global developmental delay and bilateral hearing loss, with computed tomography (CT) findings of an absent right incus lenticular process and a dilated right vestibule. Genetic testing revealed a heterozygous pathogenic variant c.152G>A (p.Trp51*) in the <i>SOX2</i> gene. <i>SOX2</i> (sex-determining region Y-box 2) is a transcription factor critical for early pituitary and hypothalamic development. However, the phenotype associated with <i>SOX2</i> pathogenic variants remains incompletely defined due to its rarity and wide phenotypic variability. Our case uniquely highlights temporal bone anomalies and a comprehensive pituitary function workup, which may contribute to a clearer understanding of <i>SOX2</i>-related phenotypic presentations. This case underscores the need to consider <i>SOX2</i> pathogenic variants in the genetic evaluation of IHH, even in the absence of ocular abnormalities.