Karyotype-phenotype relationship
分子基础 X 染色体不同的位点异常可以导致不同的体征，即表现为 不完全性 TS 控制身高的基因位于 X 染色体短臂上，具体定位于 p21 的矮小身材同源框（SHOX（short stature homeobox）基因(位于Xp及Y) Xq13～Xq26决定 TS 的体征 Xp11、Xq 近端和 Xq 远端片段决定性腺发育和功能 Xq 末端是端粒（telomere）存在的区域:Xq 末端的 缺失与重组与该类型患者继发性闭经存在密切关系，可能 是卵巢早衰的特异性基因区段。
曾经用雌雄间体、假两性畸形、真两性畸形和性反转这些术语用于描述 性发育疾病, 但有轻蔑含义。 2006年欧洲儿科内分泌协会( European Society for Pardiatric Endocrinology, ESPE)和LawsonWilkins儿科内分泌协会 (LawsonWilkins Pardiatric Endocrine Society, LWPES) 联合召开 了由内分泌学家、外科学家、遗传学家、心理学家和患者支持小组成员 参加的会议, 提出了新的术语、分类标准
Karyotype-phenotype relationship
45,X karyotype : the most likely to have congenital lymphedema. mosaicism for 45,X/46,XX or 45,X/47,XXX : the most likely to have spontaneous menarche and fertility; mosaicism for 45,X/46,XX are marginally taller than other women with Turner’s syndrome. isochromosome Xq : an increased risk for hypothyroidism and inflammatory bowel disease. a ring or marker chromosome : an increased risk of mental retardation and atypical phenotypic feature
Postnatal diagnosis
newborns :puffy hands and feet or redundant nuchal skin; should be suspected in any newborn girl with edema or hypoplastic left heart or coarctation of the aorta in midchildhood :short stature; primary or secondary amenorrhea
Mosaicism I
In routine karyotyping, 20 cells are counted (to detect mosaicism at a level of about 5 percent) (Mosaicism for a second, normal 46,XX cell population is about 15 percent ) the detection of a normal cell lineage in fewer than 5 percent of cells does not change the prognosis or the management if the diagnosis of Turner’s syndrome is suspected clinically but the result of routine testing is normal, increasing the number of cells counted to 100 and performing a skin biopsy for karyotyping of fibroblasts are indicated to rule out mosaicism or an abnormal cell lineage
处理原则:
(1) DSD的个体都应该接受性别确认,应在专家评估后确定新生 儿的性别。 ( 2)长期的治疗和随访应在有经验多学科的中心进行,在治疗小
组中应有儿科内分泌专家、外科医生、泌尿外科和妇产科专家、
遗传学家、社会工作者和医学伦理学工作者。 (3)与患者和家属进行开放式的交流,并且鼓励参加性别决定的
标准型 45，XO 病人有女性表现，但身材矮小、原发
闭经、不孕、智力一般正常或稍差，常合并有颅面（蹼 颈）、四肢（肘外翻）及心血管方面的畸形，性腺萎缩， 可退化成“索状性腺”，第二性征发育不良。 其发病机制为：女性完整的有功能的两条 X 染色体是 维持女性性腺发育及正常卵巢功能所必须的。
Lyon 假说认为 46，XX 中的一条 X 染色体失活 TS 患者表型不是 X 单体造成的（45，XO 缺失的是失 活的X），这也是 45，XO 能存活的原因。
Tuner Syndrome
北京世纪坛医院检验科细胞分子遗传组 肖文珺
性发育疾病概念及基本分类介绍 特纳综合征概述 症状和体征 诊断 核型-表型关系 治疗
性发育疾病(Disorders of sex development DSD) 是性决定和性分化异常的一组异质性遗传病, 是由 于染色体畸变或单基因突变导致的性发育遗传和内 分泌途径的改变。
thorax 胸膛 metacarpal 掌骨
constriction 缢痕 aorta 大动脉 rudimentary 不发育的 gonadal streak 性索 menstruation 月经

Hale Waihona Puke Short stature (Usually no taller than 4’8”) Obese weight (due to an underactive thyroid) Drooping eyelids Problems with breast development Short fingers and toes Extra skin on the neck (webbed neck) Swelling of the hands and feet Low set ears Soft nails that turn upward at the ends Irregular rotation of wrist and elbow joints Loss of ovarian functions (infertility) Heart defects Kidney problems Visual impairments Ear infections and hearing loss High blood pressure Weak bones

Karyotype-phenotype relationship
loss of the short arm (Xp) results in the full phenotype Very distal Xp deletions: normal ovarian function with short stature and the typical skeletal changes Loss of a region at Xp22.3 : neurocognitive problems Loss of interstitial or terminal Xq ：short stature and primary or secondary ovarian failure.
Mosaicism II
mosaicism for a cell population with a Y chromosome : at increased risk for gonadoblastoma (risk, 7 to 30 percent) in their streak gonads in those with masculinization or mosaicism for an unidentified marker: the use of flow cytometry or DNA hybridization to search for Y-chromosome material
Diagnosis of TS
Prenatal diagnosis
the finding of fetal edema on ultrasonography; abnormal levels of screening of maternal serum (triple screening) abnormal results of fetal karyotyping performed because of advanced maternal age available data suggest that prenatal cytogenetic diagnosis of TS in the absence of abnormal fetal ultrasound has a high false positive rate and seems to be a poor predictor of clinical outcome
建议使用DSD代替先前延用的雌雄间体、假两性畸形、真两性畸形 和性反转等术语,并提出按照染色体核型分析结果给DSD分类。 按照染色体的分类,将其分为性染色体异常的DSD; 46, XY DSD和 46, XX DSD等三大类。
先前使用的术语 雌雄间体 男性假两性畸形 46, XY男性性征发育不良 女性假两性畸形 XX女性呈现男性性征 真两性畸形 XX男性或 XX性反转 XY性反转 卵睾性 DSD 46, XX睾丸性 DSD 46, XY完全性性腺发育不全 46, XX DSD 现提出的术语 性发育疾病 46, XY DSD