Introduction: Kallmann Syndrome (KS) is a genetically heterogeneous disease characterised by hypogonadotrophic hypogonadism with anosmia or hyposmia. It can be associated with X-linked ichthyosis (XLI) in a contiguous gene syndrome related to a Xp22.3 region deletion, which include KAL1 and STS genes.
Case report: We report a case of a 32-year-old male with ichthyosis referred for evaluation of high height (2.07 m), overweight (BMI 29.6 kg/m2) and microgenitalia.
He had absence of secondary sexual characters. Baseline plasma levels of testosterone were 0.12 ng/ml (2.498.36), FSH 0.25 mUI 7 ml (1.512.4) and LH <0.1 mUI/ml (1.78.6). Prolactin levels were 7.67 ng/ml (4.0415.2). MRI showed hypoplastic hypophysis, ultrasound showed small testes and a bone densitometry revealed osteoporosis (spine T score −3.55). Karyotype was 46 XY. He was diagnosed of hypogonadotrophic hypogonadism associated to ichthyosis. Genomic DNA samples were extracted. A microarray-based comparative genomic hybridisation test (aCGH) was performed. The result was a pathogenic copy number DNA variant: arr(hg19)Xp22.32p22.31 (4 699 9729 427 600)xo which contains 12 genes: NLGN4X, VCX3A, HDHD1, STS, VCX, PNPLA4, MIR651, VCX2, VCX3B, KAL1, FAM9A, FAM9B. Among these genes, STS is responsible for XLI and KAL 1 gene is responsible for the X-linked form of KS. Further studies revealed that the deletion was inherited from his mother. Females with similar Xp22 deletions are phenotypically normal except for short stature, because they need only one copy of this region to be normal.
He started intramuscular testosterone undecanoate supplementation in progressive doses to achieve secondary sexual character development and continued with substitutive treatment. Three years later bone densitometry improved (spine T score −2.78 S.D.).
Conclusion: KS is a genetically heterogeneous disease that can be associated with other diseases in a contiguous gene syndrome. New genomic tests provide a better understanding and knowledge of genetic diseases, diagnosis and management. Special attention has to be drawn to complications like osteoporosis, infertility and testis cancer.
28 - 31 May 2016
European Society of Endocrinology