Rochtus Anne, Asscherickx Willeke, Timmers Marijke, Vermeer Sascha, Antonio Leen
Department of Pediatrics, University Hospitals Leuven, 3000 Leuven, Belgium.
Department of Endocrinology, University Hospitals Leuven, 3000 Leuven, Belgium.
JCEM Case Rep. 2024 Oct 23;2(11):luae195. doi: 10.1210/jcemcr/luae195. eCollection 2024 Nov.
Biallelic pathogenic variants in cause a syndrome characterized by hypogonadotropic hypogonadism, cerebellar ataxia, chorea, and cognitive impairment, a combination first described as Gordon Holmes syndrome (MIM 212840). We report 2 siblings who were referred due to absent or delayed puberty. The older sibling, a 17-year-old male, presented with absence of secondary sexual characteristics and a high-pitched voice. He had normal cognitive development and no anosmia. Clinical examination revealed Tanner stage P1/G1 and bilateral gynecomastia. Blood tests showed low gonadotropin and morning testosterone levels. His 15-year-old sister was referred due to primary amenorrhea. She had spontaneous thelarche and presented with Tanner stage P3/B3. Pituitary magnetic resonance imaging was performed on the brother due to suspicion of Kallmann syndrome, revealing a normal anterior pituitary, a hypoplastic posterior pituitary, and an extensive supratentorial leuko-encephalopathy. Whole-exome sequencing revealed a homozygous pathogenic variant in in both affected siblings. Both parents were heterozygous carriers. pathogenic variants cause a disorder characterized by combined neurodegeneration and reproductive dysfunction. Although neurological symptoms are typically recognized first, they often seem to follow the onset of hypogonadism. This highlights the need for awareness, as hypogonadotropic hypogonadism may be the initial manifestation of this severe neuroendocrine disorder, especially in males.
[基因名称]的双等位基因致病变异会导致一种综合征，其特征为低促性腺激素性性腺功能减退、小脑共济失调、舞蹈症和认知障碍，这种组合最早被描述为戈登·霍姆斯综合征（MIM 212840）。我们报告了2名因青春期缺失或延迟而前来就诊的兄弟姐妹。年长的是一名17岁男性，表现为缺乏第二性征且嗓音高亢。他认知发育正常，无嗅觉减退。临床检查显示坦纳分期为P1/G1，双侧乳腺增生。血液检查显示促性腺激素和清晨睾酮水平低。他15岁的妹妹因原发性闭经前来就诊。她有自然乳房发育，处于坦纳分期P3/B3。由于怀疑卡尔曼综合征，对哥哥进行了垂体磁共振成像检查，结果显示垂体前叶正常，垂体后叶发育不全，以及广泛的幕上白质脑病。全外显子组测序显示两名患病兄弟姐妹均存在[基因名称]的纯合致病变异。父母双方均为杂合携带者。[基因名称]的致病变异会导致一种以神经退行性变和生殖功能障碍相结合为特征的疾病。虽然神经症状通常首先被识别，但它们似乎常常在性腺功能减退发作之后出现。这凸显了提高认识的必要性，因为低促性腺激素性性腺功能减退可能是这种严重神经内分泌疾病的初始表现，尤其是在男性中。
