Department of Endocrinology, Great Ormond Street Hospital for Children, London, United Kingdom.
Section of Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Program, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
J Clin Endocrinol Metab. 2018 Jun 1;103(6):2079-2082. doi: 10.1210/jc.2017-02671.
45,X/46,XY mosaicism is a disorder of sex development leading to abnormal gonadal development and to unpredictable genital phenotype, growth, and pubertal development.
A 2-year-old male presented with a right impalpable testis. Blood karyotype was 46,XY. A laparoscopy performed for right orchidopexy revealed a right streak gonad with Mullerian structures, whereas on the left side, a normal descended testis was present. The karyotype of the removed gonad was 45,X/46,XY. The child grew along the second centile, within the midparental height (MPH) range, until the time of puberty, when linear growth worsened due to a lack of a pubertal growth spurt, and growth hormone (GH) therapy was initiated. He developed spontaneous puberty (13 years of age) and showed normal pubertal progression. However, from the age of 15 years, he had low normal testosterone, raised follicle-stimulating hormone, and reduction of inhibin B, possibly suggestive of declining testicular function. His final height was -2.24 standard deviation score (SDS) (-2.4 SDS at GH start; MPH -1.6 SDS).
Our case describes a mild male phenotype associated with 45,X/46,XY mosaicism characterized by unilateral cryptorchidism, spontaneous onset of puberty, and normal blood karyotype. The case illustrates the difficulties inherent in making a diagnosis of 45,X/46,XY mosaicism when there is no genital ambiguity and makes the point that growth and testicular impairment may occur, mostly manifesting during adolescence. An early diagnosis is crucial to initiate careful monitoring for growth and pubertal disorders, increased tumor risk, and fertility issues commonly seen in these children.
45,X/46,XY 嵌合体是一种性发育障碍，导致性腺发育异常和不可预测的生殖器表型、生长和青春期发育。
一名 2 岁男性，右侧隐睾。血核型为 46,XY。为右侧睾丸固定术进行腹腔镜检查，发现右侧条索状性腺有苗勒管结构，而左侧则存在正常下降的睾丸。切除性腺的核型为 45,X/46,XY。患儿的生长一直处于第二百分位，在中父母身高（MPH）范围内，直到青春期，由于缺乏青春期生长突增，线性生长恶化，开始生长激素（GH）治疗。他自发进入青春期（13 岁），并表现出正常的青春期进展。然而，从 15 岁开始，他的睾酮水平正常偏低，促卵泡激素升高，抑制素 B 减少，可能提示睾丸功能下降。他的最终身高为-2.24 个标准差评分（SDS）（GH 开始时为-2.4 SDS；MPH 为-1.6 SDS）。
我们的病例描述了一种与 45,X/46,XY 嵌合体相关的轻度男性表型，其特征为单侧隐睾、自发青春期开始和正常的血核型。该病例说明了在没有生殖器模糊的情况下，诊断 45,X/46,XY 嵌合体所固有的困难，并指出生长和睾丸损害可能发生，主要在青春期表现出来。早期诊断对于开始仔细监测生长和青春期障碍、肿瘤风险增加以及这些儿童常见的生育问题至关重要。
