Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
Am J Med Genet A. 2010 Dec;152A(12):3143-7. doi: 10.1002/ajmg.a.33720.
We describe two patients with Pallister-Hall syndrome (PHS) with genital abnormalities: a female with hydrometrocolpos secondary to vaginal atresia and a male with micropenis, hypoplastic scrotum, and bilateral cryptorchidism. Nonsense mutations in GLI3 were identified in both patients. Clinical and molecular findings of 12 previously reported patients who had GLI3 mutations and genital abnormalities were reviewed. Genital features in the male patients included hypospadias, micropenis, and bifid or hypoplastic scrotum, whereas all the females had hydrometrocolpos and/or vaginal atresia. No hotspot for GLI3 mutations has been found. The urogenital and anorectal abnormalities associated with PHS might be related to dysregulation of SHH signaling caused by GLI3 mutations rather than hormonal aberrations. We recommend that clinical investigations of genital abnormalities are considered in patients with PHS, even those without hypopituitarism.
我们描述了两例伴有生殖器异常的 Pallister-Hall 综合征（PHS）患者：一例女性患者因阴道闭锁而出现先天性中肾管积水，一例男性患者表现为小阴茎、发育不良的阴囊和双侧隐睾。两名患者均存在 GLI3 无义突变。我们回顾了 12 例先前报道的具有 GLI3 突变和生殖器异常的患者的临床和分子发现。男性患者的生殖器特征包括尿道下裂、小阴茎和分叉或发育不良的阴囊，而所有女性患者均存在先天性中肾管积水和/或阴道闭锁。尚未发现 GLI3 突变的热点。与 PHS 相关的泌尿生殖和肛门直肠异常可能与 GLI3 突变引起的 SHH 信号通路失调有关，而不是激素异常。我们建议，即使没有垂体功能减退症，对于 PHS 患者也应考虑进行生殖器异常的临床检查。
