关键词: 卡尔曼综合征, 性腺功能减退, 嗅觉障碍, 全外显子基因测序, 脉冲式GnRH治疗

Abstract:

Objective To analyze the clinical and genotypic characteristics of children with Kallmann syndrome (KS), and to strengthen clinicians' understanding of the disease. Methods The clinical characteristics, whole-exome gene sequencing results, and treatment outcomes of 20 KS patients were retrospectively analyzed. Results Among the 20 patients, 17 were boys and 3 were girls. The mean age at diagnosis was 13.13 years old. Male children presented micropenis with small testicular size and history of bilateral cryptorchidism, while female patients presented primary amenorrhea and retardation of breast development. The results of Chinese odor recognition test indicated that 93.75% (15/16) children had olfactory disorder. Children with KS may have other systemic manifestations, including neurodevelopmental delay, mental retardation, phalangeal abnormalities, hearing impairment, and congenital cleft lip and palate. Among the 19 patients who underwent whole-exome gene sequencing, 12 variation sites in 6 genes were found, including FGFR1, CHD7, SOX10, KAL1, PROKR2 and SOX2. The molecular diagnosis rate was 63.16% (12/19). Testicular size, penile length, penile girth, T, LH and FSH were significantly improved after receiving pulsatile GnRH pump treatment, and there were no obvious adverse reactions. Conclusions The application of Chinese odor recognition tests can more accurately evaluate olfactory function in children with KS. The whole-exome gene sequencing technology is helpful to improve the molecular diagnosis of the disease, so as to diagnose the children with this rare disease as early as possible. Pulsatile GnRH pump therapy promotes sexual development in children with KS without obvious adverse effects.

Key words: Kallmann syndrome, hypogonadism, olfactory disorder, whole-exome gene sequencing, pulsatile GnRH therapy