Two females presenting primary amenorrhea diagnosed with Kallmann syndrome caused by novel FGFR1 variants.

Primary amenorrhea as the common symptom has a complicated etiology, and genetic disorders are non-negligible. Kallmann syndrome (KS) is a rare inherited disease characterized by hypogonadotropic hypogonadism and anosmia. KS is uncommon in women and is an unusual cause of primary amenorrhea. Herein, we described the clinical features in two female patients presenting primary amenorrhea without puberty. Magnetic resonance imaging showed dysplastic or absent olfactory bulbs and tracts. Eventually, they were diagnosed with KS caused by FGFR1 novel variants, c.315_317delCCCinsTT and c.1081G>A, using whole-exome sequencing (WES). We emphasize that KS should be considered in females presenting primary amenorrhea and anosmia, and recommend that WES should be a priority in the patients presenting primary amenorrhea without secondary sex characteristics.