ESPE Abstracts

Objective: to assess olfactory bulbs sizes and define the most common molecular defects in adolescents with congenital isolated hypogonadotropic hypogonadism.

Materials and Methods: Single-centre comparative study. 36 patients were included. The main group consisted of 21 patients with mean age of 15.9 years (17 boys, 4 girls) with congenital isolated hypogonadotropic hypogonadism (IHH): 13 patients with Kallmann syndrome (KS), 8 – with normosmic isolated hypogonadotropic hypogonadism (nIHH). Kallmann syndrome was diagnosed due to complaints of hypo- or anosmia. Olfactory bulbs width and height were assessed via MRI. Molecular-genetic studies were provided in all patients from main group. 15 patients were enrolled as controls (6 girls, 9 boys). Groups were matched for age, height and weight.

Results: Bilateral olfactory bulb hypoplasia was diagnosed in 7 out of 21 patients from main group. Bilateral aplasia was found in 4 patients. Olfactory bulb defects were found in 7 out of 8 nIHH children with no complains of hypo- or anosmia. Only 1 adolescent with hypogonadotropic hypogonadism had normal olfactory bulb size. Height and width of olfactory bulbs were significantly smaller in main group in comparison with controls (P<0.05 via Mann–Whitney U test). Median of right bulb height was 1.0 mm [0.2;1.2] in patients from the main group vs. 3.0 [2.5;3.2] in control group. Median of right bulb width was 1,0 mm [0.2;1.7] in patients from the main group vs. 2.5 [2.0;3.0] in control group. Median of left olfactory bulb height was 0.8 mm [0.0;1.1] in main group vs. 3.0 [2.7;3.2] in controls. Median of left olfactory bulb width was 0.4 mm [0.0;1.1] in main group vs. 2.5 [2.0;3.0] in comparison with control group. There were no statistically significant differences in olfactory bulb sizes between patients with KS and nIHH (P>0.05). Molecular defects were identified in 9 patients from main group: defects in FGFR1 were found in 4 out of 9 patients, СHD7 - 3, KAL1-1, FGF17 - 1. 5 defects were identified as variants of uncertain significance, 2 as likely pathogenic and 2 as pathogenic.

Conclusion: Bilateral olfactory bulb disorder hypoplasia is a reliable sign of hypogonadotropic hypogonadism: every third adolescent with congenital IHH had bilateral olfactory bulbs hypoplasia. All pathogenic variants were identified in FGFR1 and associated with uni/bilateral hypoplasia. Olfactory bulb defects were identified in 87.5% patients with no complaints of smell disorder, including 2 cases of bilateral aplasia.