Endocrine Abstracts

Kallmann syndrome is a rare congenital hypogonadotropic hypogonadism with variable degrees of hyposomia to anosmia. This syndrome can be transmitted as autosomal dominant, autosomal recessive and X-linked inheritance pattern. We are reporting two cases of young male siblings (17 and 16 years old) who are the offspring of unrelated parents, presenting with delayed puberty and both were complaining of hyposmia. Their older brother, aged 24 years, was diagnosed with isolated hypogonadotrophic hypogonadism. Both patients had eunchoid habitus with small penis and testis with Tanner stage 1. They had a history of cryptorchidism which was corrected with orchidopexy at an early age. The older sibling had unilateral congeital ptosis. Upon further testing, they were found to have hypogonadotropic hypogonadism with severely low Testosterone and undetectable Luteinizing hormone and Follicle stimulating hormone. Other pituitary axes were intact. Pituitary MRI showed normal pituitary with normal olfactory nerves. Chromosomal analysis of both siblings showed 46 XY karyotype with hemizygous likely pathogenic variant was identified in Kal 1 (ANOS1) gene, consistent with a genetic diagnosis of X linked hypogonadotropic hypogonadism type 1. Androgen therapy with testosterone had been initiated for both siblings to induce secondary sexual features. Ptosis was reported by Reardon at 2007 in case series of 2 siblings with Kallmann syndrome. This was the only documented cases in literature to link ptosis to Kallmann syndrome. To our knowledge our case is the second to report this association.The presence of a family of three brothers with Kallman syndrome and the association with ptosis are unusual