Congenital isolated hypogonadotropic hypogonadism (CHH), is a condition characterized by a defect in development, migration and action of GnRH neurons. Numerous genes are involved in CHH. It can present with anosmia, hyposmia or normosmia. Two cases presented to our department with late onset delayed puberty. First case was a 29 year old with absence of secondary sexual characters along with micropenis and anosmia. His younger brother, 22 year old had similar complaints and findings. Both cases were evaluated. They were detected to have isolated hypogonadotropic hypogonadism. All other pituitary hormone analysis done showed normal results. MR Imaging showed characteristic absence of olfactory bulb in one case and hypoplasia in the other. Genetic analysis (Clinical Exome sequencing) for 39 genes related to CHH was done. In genetic analysis we found similar heterozygous mutation at same location in both the brothers. The mutation found in CHD7 gene at exon 2 variant 1565G>T (p.Gly522Val) which was confirmed with Sangers sequencing. Kallmann syndrome with classic presentation usually has defects in KAL1 gene, but we found mutation in CHD7 gene with Kallmann phenotype without classic features of Charge syndrome which may be the mild phenotypic spectrum of Charge syndrome. For the first time we report a case of heterozygous mutation with pathogenic phenotypic spectrum. Further research is mandated to confirm this type of heterozygous mutation.
18 - 21 May 2019
European Society of Endocrinology