Jongmans M C J, van Ravenswaaij-Arts C M A, Pitteloud N, Ogata T, Sato N, Claahsen-van der Grinten H L, van der Donk K, Seminara S, Bergman J E H, Brunner H G, Crowley W F, Hoefsloot L H
Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Clin Genet. 2009 Jan;75(1):65-71. doi: 10.1111/j.1399-0004.2008.01107.x. Epub 2008 Nov 17.
Kallmann syndrome (KS) is the combination of hypogonadotropic hypogonadism and anosmia or hyposmia, two features that are also frequently present in CHARGE syndrome. CHARGE syndrome is caused by mutations in the CHD7 gene. We performed analysis of CHD7 in 36 patients with KS and 20 patients with normosmic idiopathic hypogonadotropic hypogonadism (nIHH) in whom mutations in KAL1, FGFR1, PROK2 and PROKR2 genes were excluded. Three of 56 KS/nIHH patients had de novo mutations in CHD7. In retrospect, these three CHD7-positive patients showed additional features that are seen in CHARGE syndrome. CHD7 mutations can be present in KS patients who have additional features that are part of the CHARGE syndrome phenotype. We did not find mutations in patients with isolated KS. These findings imply that patients diagnosed with hypogonadotropic hypogonadism and anosmia should be screened for clinical features consistent with CHARGE syndrome. If such features are present, particularly deafness, dysmorphic ears and/or hypoplasia or aplasia of the semicircular canals, CHD7 sequencing is recommended.
卡尔曼综合征（KS）是低促性腺激素性性腺功能减退与嗅觉缺失或嗅觉减退的组合，这两个特征在CHARGE综合征中也经常出现。CHARGE综合征由CHD7基因突变引起。我们对36例KS患者和20例嗅觉正常的特发性低促性腺激素性性腺功能减退（nIHH）患者进行了CHD7分析，这些nIHH患者排除了KAL1、FGFR1、PROK2和PROKR2基因的突变。56例KS/nIHH患者中有3例存在CHD7新发突变。回顾性分析发现，这3例CHD7阳性患者表现出CHARGE综合征的其他特征。CHD7突变可存在于具有CHARGE综合征表型部分其他特征的KS患者中。我们在孤立性KS患者中未发现突变。这些发现表明，对于诊断为低促性腺激素性性腺功能减退和嗅觉缺失的患者，应筛查与CHARGE综合征一致的临床特征。如果存在此类特征，特别是耳聋、耳部畸形和/或半规管发育不全或缺失，建议进行CHD7基因测序。
