Two cases of Kallmann syndrome caused by a novel mutation in ANOS1: A case report

Anosmin 1 (ANOS1) was the first gene to be associated with Kallmann syndrome (KS). We identified 2 cases of KS caused by novel mutations in ANOS1, which expands the spectrum of known pathogenic mutations of this gene. We also conducted a literature review on KS pathogenesis, manifestations, and therapeutic options to aid clinicians in the early diagnosis and treatment of this condition.

Two male patients presented with penile hypoplasia, reduced olfactory function, and delayed puberty progression.

Both patients exhibited olfactory dysfunction, and one presented with bilateral hand movements. Both also had low levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and androgens. Magnetic resonance imaging revealed small pituitary volumes, thin pituitary stalks, and small olfactory bulbs and tracts. Whole-exome sequencing revealed an ANOS1 c.90_100dupTGCTGCGCGGC (p.Arg34Leufs*25) variant in both patients. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed, leading to the diagnosis of KS in both patients.

Both patients received pulsatile GnRH pump therapy.

After pulsatile GnRH pump therapy, LH, FSH, and testosterone levels, as well as penile lengths and testicular volumes, increased significantly in both patients.

This is the first report of 2 cases of KS caused by a new mutation at the ANOS1 locus, expanding the mutation spectrum of ANOS1 and providing data on the clinical and genetic phenotypes of KS, which will assist clinicians in the early diagnosis and treatment of KS.