Endocrine Abstracts

Two identical twins aged 20 were referred for investigation and treatment of delayed puberty. They were otherwise fit and well, with no significant past medical history. On presentation, both were tall, eunuchoid with no secondary sexual characteristics. Twin A had undergone orchidopexy for an undescended testicle, but had a normal sense of smell on testing. Twin B had normal pre-pubertal external genitalia, but reported anosmia. Neither exhibited synkinesis, abnormal dentition, high arched or cleft palate or hearing impairment. Initial investigations showed hypogonadotrophic hypogonadism, otherwise normal baseline pituitary function, and a normal 46XY karyotype. Twin A had a raised alkaline phosphatase at diagnosis, indicating a degree of bone turnover, while that of Twin B was normal. Magnetic resonance imaging of the pituitary was normal in both, as were renal tract ultrasound scans. A clinical diagnosis of Kallmann’s syndrome was made and they were started on increasing doses of injectable testosterone replacement therapy over the next 18 months, with varying effect. At equal doses of testosterone, both had increased axillary and pubic hair, but only Twin A reported increased libido and early morning erections. Kallmann’s syndrome is a heterogeneous condition characterised by abnormal development of the olfactory bulbs and tracts, with clinical anosmia and hypogonadotrophic hypogonadism. About 30% of all Kallmann’s syndrome cases are attributable to mutations in the five KS genes identified to date: FGFR1, FGFB, PROKR2, PROK2, and KAL1. Inheritance is usually either autosomal dominant or sex linked, though the clinical features dissociate and severity varies widely within some families. Possible digenic inheritance with compound heterozygosity has also been reported perhaps explaining the variable inheritance and penetrance in some families. This is the second case of two apparently genetically identical individuals with non-identical phenotypic expression of Kallmann’s syndrome. This provides a novel opportunity to investigate the causes of this condition.