The relationship between olfactory function, rhinencephalon and forebrain changes in Kallmann syndrome (KS) have not been adequately investigated. We evaluated a large cohort of male KS patients using Sniffin’ Sticks and MRI in order to study olfactory bulb (OB) volume, olfactory sulcus (OS) depth, cortical thickness close to the OS, and olfactory phenotype.

Olfaction was assessed administering Sniffin’ Sticks®, in 38 KS patients and 17 controls (by means of Screening 12 test®). All subjects underwent magnetic resonance imaging (MRI) to study OB volume, sulcus depth, and cortical thickness.

Compared to controls, KS patients showed smaller OB volume (p<0.0001), reduced sulcus depth (p<0.0001), and thicker cortex in the region close to the OS (p<0.0001). Anosmic KS patients had smaller OB than controls and hyposmic KS patients; there was no difference between hyposmic KS patients and controls. OB volume correlated with Sniffin’ Sticks score (r = 0.64; p < 0.001), OS depth (p<0.0001) and, inversely, with cortical thickness changes (p<0.0001). Sniffin’ Sticks showed an inverse correlation with cortical thickness (r = −0.5; p<0.0001) and a trend toward a statistically significant correlation with OS depth.

The present study provides further evidence of the strict relationship between olfaction and OB volume. The strong correlation between OB volume and the overlying cortical changes highlights the key role of rhinencephalon in forebrain embryogenesis.