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Objective To evaluate the efficacy and adverse reactions of BRAF inhibitor vermorafenib on the treatment of refractory craniopharyngioma carrying BRAF-V600E mutation. Methods Clinical data of two patients with refractory craniopharyngiomas (CP) were recorded and reviewed. The patients were followed up for 3-5 years. Literature on CPs receiving BRAF or BRAF/MEK therapy was reviewed. Results 1)Papillary CP progressed after multiple operations and radiotherapy in two patients. Further treatments were very difficult. 2)The presence of BRAF-V600E mutation in the tumor was confirmed, and vermorafenib was administered for 6.5-7.5 months. Tumor volumes remarkably shrank by 95%-99%. No tumor relapse was observed during the follow-up of 3-5 years after discontinuation of vemurafenib. 3)The main adverse reaction was rash, which was dose dependent. 4)Literature review showed the volume shrank by 50%-100% in 33/34 tumors during BRAF or BRAF/MEK inhibitor therapy. Conclusions BRAF inhibitor vemurafenib is effective in treating refractory craniopharyngioma carrying BRAF-V600E mutation with endurable side effects, which may bring some changes to the management of CP in future.

Objective To investigate whether multiple gene mutations were existed to cause congenital hypogonadotropic hypogonadism(CHH), by screening genes in CHH patients with FGFR1 mutations. Methods FGFR1 mutations were identified in 15 CHH patients. Other CHH-related genes were screened in these patients. Bioinformatics software was used to analyze the pathogenicity of gene variant. Results 1)Mutations in FGFR1 were inherited from parents in 9 patients (inherited mutation group)in spite of the fact, their parents showed normal reproductive axis function. 2)In the inherited mutation group, 6 patients harbored another mutation including PROKR2(W178S), FGF8(T121N), HS6ST1(P242L), SEMA3A(R734W), LZTR1(Q10Rfs*15) and FGFR1 compound heterozygous mutation. Multiple gene mutations may lead to CHH. 3)Six patients were found to have de novo mutations in FGFR1(de novo mutation group) but not no other pathogenic CHH related gene mutations. Conclusions FGFR1 mutations inherited from parents may require another blow from CHH-related genes to cause CHH. This study expands our understanding of the pathogenesis of CHH caused by digenic mutation.

Objective To analyze the sex hormonal therapy present status in patients with Prader-Willi syndrome (PWS) and to provide guidance for the future sex hormone application. Methods Pubertal development, abnormal behavior, bone mineral density, sex hormone treatment and parents' attitude to sex hormone application were analyzed by a self-designed questionnaire. Results A total of 41 PWS patients were included (21 males and 20 females) and the median age was 15 years old (13-24 years). For boys, all had cryptorchidism, of which 6 patients (28.6%) had no pubertal development. None of the patients were receiving additional androgen therapy. For girls, 13 (65%) had primary amenorrhea. Only 2 patients had received or was continuing estrogen replacement therapy. Considering the inconveniences of drug application and other reasons, 16 cases (39%) of parents were unwilling to undergo sex hormone therapy. Conclusions Almost all patients with PWS are hypogonadism. Lack of medical recommendations and limited knowledge on sex hormones for their parents, may contribute to low prevalence of sex hormone therapy in this population.