Split hand/foot malformation: a potential clue to underlying FGFR1 mutation in patients with isolated congenital hypogonadotropic hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) is characterised by absent or arrested pubertal development due to abnormal hypothalamic gonadotropin-releasing hormone (GnRH) secretion or its action. A number of candidate genes (more than 20) have been identified to underlie CHH either acting alone or in combination. The prototype example of isolated CHH is Kallmann syndrome (KS) which has four subtypes: type 1 (mutation in anosmin gene), type 2 (mutation in fibroblast growth factor receptor 1 (FGFR1)), type 3 ((mutation in prokinecitin receptor 2 (PROKR2)) and type 4 (mutation in prokinecitin). Loss-of-function mutations of FGFR1 or KS2 are responsible for about 10%–12% of patients with CHH. FGFR1 is expressed in a number of tissues, including the brain and skeletal system. Spontaneous reversal of CHH …