Turner syndrome patients with a ring X chromosome

A patient with clinical features of Turner syndrome and a 45,X karyotype in repeated blood cultures was re-evaluated when she spontaneously entered puberty. A ring X cell line was found in a small proportion of fibroblasts. A review of 35 previously published ring X cases is presented. All are mosaic, the major cell line in most cases being 45,X. There is wide variation in the frequency with which the abnormalities associated with Turner syndrome are found in these patients. All have short stature. Some are sexually developed and fertile. Cardiovascular anomalies are uncommon. This phenotypic variation may have at least two causes: the size of the deleted portion at each end of the X chromosome, and the relative frequency and distribution of 45,X and 46,X,r(X) cell lines in various body tissues.     

Familial Turner syndrome

A 28-year-old Turner female with secondary amenorrhea is described, who showed 45,X/46,X,del(Xp) mosaicism in her blood lymphocytes and a 46,X,del(Xp) karyotype only in her ovaries. 45,X/46,XX mosaicism was found in the patient's mother, who presented short stature, mild Turner dysmorphism and had a normal reproductive life-span. Phenotypic implications of the cytogenetic findings in the patients are discussed, and literature data on fertility in Turner syndrome are briefly reviewed.     

7号染色体臂间倒位伴Turner综合征家系分析

目的研究7号染色体臂间倒位的遗传机制.方法患儿及父母作染色体检查,并对患儿的家系进行调查.结果患儿的染色体核型为46,XX,inv(7)(p22q11)/45,X,inv(7)(p22q11),其中46,XX,inv(7)(p2q11),85%,45,X,inv(7)(p22q11),15%.父亲的核型为46,XY,inv(7)(p22q11),母亲的染色体正常,患儿的母亲第1胎为3月自然流产,家系中其他成员均无流产史,母系成员中身材均偏矮小.结论染色体臂间倒位能引起流产和畸胎,应作产前诊断.     

Turner syndrome may be associated with hepatic adenoma

Turner syndrome, caused by complete or partial loss of an X chromosome, is marked by a range of clinical manifestations including short stature, cardiovascular and renal disease. Hepatic involvement is an increasingly recognized concern. Steatosis and elevated transaminases are commonly observed in this population, but case reports have also described hepatic adenoma. Hepatic adenomas are rare, occurring in one per million people in the general population. They are typically benign but malignant transformation or rupture can occur. We sought to investigate whether Turner syndrome is associated with hepatic adenoma. Patients with Turner syndrome encountered at a single, academic institution between 2006 and 2020 were identified using ICD-10 codes and demographic, medication, laboratory, and imaging data were analyzed. Of the 228 patients identified, 46.9% had liver function testing, which were abnormal in 48.6%. Five of 77 patients with hepatic imaging had abnormalities. Three patients (1.3%) had hepatic adenoma, one after presenting in hemorrhagic shock due to rupture. These findings suggest that patients with Turner syndrome may have an increased risk for developing hepatic adenoma. Annual monitoring of liver function tests is already recommended in Turner syndrome. The addition of periodic hepatic imaging may also be beneficial.     

Parental origin of the X chromosome, X chromosome mosaicism and screening for "hidden" Y chromosome in 45,X Turner syndrome ascertained cytogenetically

Our study confirms the finding that about 85% of X chromosomes in Turner girls are maternally derived. A new observation is the detection of a high frequency of mosaicism (15%) in Turner girls who by cytogenetic analysis were thought to have a pure 45,X karyotype. DNA examination of the material was done by hybridization with digoxigenin labelled, non-radioactive probes, and PCR products for microsatellite analysis were run on polyacrylamide gels. We screened for the presence of "hidden" Y chromosome mosaicism, using the primers SRY, ZFY, DYZ3, DYZ1 and DYS132. Contrary to other reports using the PCR technique to unravel "hidden" Y chromosome mosaics, we did not find any positive cases. A precise technical protocol for these new techniques is given, and the advantages are discussed.     

45,X/46,X,+mar核型Turner综合征患儿额外小标记染色体来源和形态研究

遗传学特征,以指导遗传咨询、产前诊断和确定临床治疗方案.     

Adult Turner syndrome associated with chylous ascites and vascular anomalies

An adult female with Turner syndrome presented with severe lymphedema and chylous ascites. In addition, the patient was found to have a right-sided aortic arch and a left-sided inferior vena cava. Although lymphedema is common in infants with Turner syndrome is previously unreported. In this patient, a peritoneo-venous shunt appeared to be beneficial.     

Turner综合征患儿标记染色体的来源研究

目的 了解Turner综合征患儿标记染色体的来源，以指导遗传咨询及治疗。方法 在染色体核型分析的基础上，对32例Turner综合征患者进行回顾性分析。对3例含有标记染色体的患儿进一步用荧光原位杂交技术研究标记染色体的来源。结果 3例含有标记染色体的Turner综合征患儿中，确定1例患儿的标记染色体来源于Y染色体，含有性别决定基因；1例来源于X染色体；另外1例未能确定其来源，该标记染色体可能来源于性染色体的其他片段或其他端着丝粒染色体。结论 Turner综合征患者的标记染色体大多来源于性染色体（X染色体、Y染色体），也可能来源于其他端着丝粒染色体。有必要同时应用X染色体和Y染色体特异性探针对Turner综合征患者进行标记染色体的荧光原位杂交分析，以明确标记染色体的来源。     

Fertility and pregnancy outcome in Danish women with Turner syndrome

The aim of the investigation was to study fertility in Danish women diagnosed with Turner syndrome (TS), and to describe their offspring. In total, 410 women in the fertile age were registered in the Danish Cytogenetic Central Register with TS between January 1973 and December 1993. Their karyotype were as follows: 49% with 45,X, 23% with mosaicism and a structural abnormality of the second X, 19% with 45,X/46,XX mosaicism, and 9% with 46,XX and a structural abnormality of the second X. Thirty-three women, one with 45,X, 27 with mosaicism and 5 with 46,XX and a structural abnormality of the second X, gave birth to 64 children. Two women had become pregnant after in vitro fertilization, including a woman with 45,X after an egg donation. Thus, 31 women(7.6%) had achieved at least one spontaneous pregnancy, but 48% of the fertile women registered with 45,X/46,XX had 45,X in less than 10% of the analysed cells. Twenty-five of the 64 children had a chromosome analyzed. Six of the 25 examined children, including three siblings, had chromosomal aberrations. No case of Down's syndrome was present, and only two children had malformations. Fertility in women registered with TS is higher than earlier reported. However, only women with 45,X/46,XX mosaicism or 46,XX and structural abnormality of the second X, gave birth to live children after spontaneous pregnancies.     

Measurement of body fat in Turner syndrome

Fourteen individuals with the Turner syndrome (gonadal dysgenesis with X chromosome chromosome abnormalities) were evaluated for obesity using hydrostatic weighing and skinfold measurements. While skinfold estimates of body fat correlated well with clinical impression, hydrostatic weighing appeared to falsely overestimate percent body fat. We suggest that reduced skeletal mass and/or occult lymphedema in Turner syndrome may invalidate the formula used to calculate percent body fat derived from hydrostatic weights. In this population and possibly in other disorders where skeletal mass is reduced from the normal, the use of hydrostatic weighing may be inappropriate.     

Telomeric fusion and chromosome instability in multiple tissues of a patient with mosaic Ullrich-Turner syndrome

We describe the cytogenetic evolution of multiple cell lines in the gonadal tissue of a 10-year-old girl with mosaic Ullrich-Turner syndrome (UTS) involving clonal telomeric associations (tas) of the Y chromosome. G-band analysis of all tissues showed at least 2 cell lines; 45, X and 46,X,tas(Y;21)(q12;p13). However, analysis of left gonadal tissue of this patient showed the evolution of 2 additional cell lines, one designated 45,X,tas(Y;21)(q12;p13),−22 and the other 46,X,tas(Y;21)(q12;p13),+tas(Y;14)(q12;p13),−22. Fluorescence in situ hybridization (FISH) analysis of interphase nuclei from uncultured gonadal tissue confirmed the findings of aneuploidy in the left gonadal tissue and extended the findings of aneuploidy to the tissue of the right gonad. The chromosome findings in the gonadal tissue of this patient suggest a preneoplastic karyotype relating to several distinct tumor associations. The clonal evolution of telomeric fusions indicates chromosome instability and suggests the extra copy of the Y chromosome may have resulted from a fusion-related malsegregation. In addition, the extra Y suggests low-level amplification of a putative gonadoblastoma gene, while the loss of chromosome 22 suggests the loss of heterozygosity for genes on chromosome 22. This case demonstrates the utility of the study of gonadal tissue in 45,X/46,XY UTS patients, and provides evidence that clonal telomeric fusions may, in rare cases, be associated with chromosomal malsegregation and with the subsequent evolution of unstable karyotypes. Am. J. Med. Genet. 69:383–387, 1997. © 1997 Wiley-Liss, Inc.     

Detection and incidence of cryptic Y chromosome sequences in Turner syndrome patients

The presence of Y chromosome sequences in Turner syndrome (TS) patients may predispose them to gonadoblastoma formation with an estimated risk of 15–25%. The aim of this study was to determine the presence and the incidence of cryptic Y chromosome material in the genome of TS patients. The methodology involved a combination of polymerase chain reaction (PCR) and nested PCR followed by Southern blot analysis of three genes—the sex determining region Y (SRY), testis specific protein Y encoded (TSPY) and RNA binding motif protein (RBM) (previously designated as YRRM) and nine additional STSs spanning all seven intervals of the Y chromosome. The methodology has a high sensitivity as it detects one 46, XY cell among 10⁵ 46, XX cells. Reliability was ensured by taking several precautions to avoid false positive results. We report the results of screening 50 TS patients and the identification of cryptic Y chromosome material in 12 (24%) of them. Karyotypes were divided in four groups: 5 (23.8%) patients out of the 21 TS patients which have the 45, X karyotype (group A) also have cryptic Y sequences; none (0%) of the 7 patients who have karyotypes with anomalies on one of the X chromosomes have Y mosaicism (group B); 1 (6.3%) of the 16 patients with a mosaic karyotype have Y material (group C); and 6 (100%) out of 6 patients with a supernumerary marker chromosome (SMC) have Y chromosome sequences (group D). Nine of the 12 patients positive for cryptic Y material were recalled for a repeat study. Following new DNA extraction, molecular analysis was repeated and, in conjunction with fluorescent in situ hybridization (FISH) analysis using the Y centromeric specific probe Yc-2, confirmed the initial positive DNA findings. This study used a reliable and sensitive methodology to identify the presence of Y chromosome material in TS patients thus providing not only a better estimate of a patient's risk in developing either gonadoblastoma or another form of gonadal tumor but also the overall incidence of cryptic Y mosaicism.     

Familial Turner syndrome with an X;Y translocation mosaicism: Implications for genetic counseling

Spontaneous fertility is rare among patients with Turner syndrome and is most likely in women with mosaicism for a normal 46,XX cell line. We report an unusual case of familial Turner syndrome with mosaicism for a novel X;Y translocation involving Xp and Yp. The chromosomal analysis was carried out through cytogenetics and molecular karyotyping using a SNP array platform. The mother, a Turner syndrome woman, diagnosed in midchildhood because of short stature, was found to have a 45,X/46,X,der(X)t(X;Y)(p11.4;p11.2) karyotype, with a predominant 45,X cell line. Her parents decided against prophylactic gonadectomy, generally recommended at an early age when Y chromosome has been identified, because at age 13, she had spontaneous puberty and menarche. She reached a final height of 154 cm after treatment with growth hormone. At age 24, she became spontaneously pregnant. She had a mild aortic coarctation and close follow-up cardiac evaluation, including cardiac magnetic resonance imaging, had been performed during her pregnancy, which progressed uneventfully, except for intra-uterine growth retardation. Prenatal diagnosis revealed a female karyotype, with transmission of the maternal translocation with an unexpected different mosaic:47,X,der(X)t(X;Y)x2/46,X,der(X)t(X;Y) karyotype. This complex and unusual karyotype, including a mosaic partial trisomy X and a non-mosaic Xpter-Xp11.4 monosomy, results in transmission of Turner syndrome from mother to daughter. At birth, the girl had normal physical examination except for growth retardation. This family illustrates the complexity and difficulties, in term of patient counseling and management in Turner syndrome, in determining ovarian status, fertility planning, risks associated with pregnancies, particularly when mosaicism for Y material chromosome is identified.     

FISH技术在一例45,X/46,X,i（Xq）Turner综合征中的研究

目的应用荧光原位杂交技术（fluorescence in situ hybridization,FISH）分析一例45,X/46,X,i（Xq）嵌合体,并探讨其形成机理,临床表型与染色体核型的关系。方法通过染色体常规G显带技术,并联合FISH技术,选用X染色体着丝粒特异DNA探针（CSPX）和X染色体长臂全涂抹探针（Xq）,进一步确认异常染色体的来源。结果 G显带分析该患者染色体核型为45,X/46,X,i（Xq）,FISH技术证实了该异常染色体为Xq等臂染色体。结论 X短臂单体长臂三体型Turner综合征患者的临床表型与其染色体核型相关;在常规G显带的基础上,应用FISH技术可准确识别异常染色体,对明确诊断及后续治疗有指导意义。     

Phenotypic and genotypic variability in monozygotic triplets with Turner syndrome

Turner syndrome (TS) is a common disorder (1/2500 and 1/5000 female births) which is diagnosed at birth in approximately 20% of patients and during childhood (usually due to growth retardation) or later, (due to lack of pubertal development) for the remaining patients. Here we present a cytogenetic and molecular analysis of three monozygotic sisters. The diagnosis of TS was done for one of them (patient 1) who presented with a typical Turner phenotype. A first karyotype was established as normal and a second karyotype (carried out on 200 cells) revealed a 45,X/46,XX mosaicism with 6% of cells with a 45,X karyotype. Lymphocyte karyotype analysis showed the same mosaicism pattern for the two other sisters, one of them exhibiting only a mild (patient 2) and the other no clinical features of Turner syndrome (patient 3). Karyotype analysis was this time conducted on fibroblasts and showed that the 45,X/46,XX mosaicism pattern correlated with the clinical phenotype with 99, 43 and 3% of 45,X cells in patients 1, 2, and 3, respectively.
These data suggest that different tissues other than lymphocytes should be subjected to a karyotype analysis when the observed genotype does not correlate with the clinical phenotype.     

Physiological arousal in females with fragile X or Turner syndrome

Physiological arousal was measured in 12- to 22-year-old females with either fragile X, Turner syndrome, or neither disorder to explore potential differences in the manifestation of arousal and anxiety in adolescents and young women. Physiological arousal was measured at baseline and during performance on mental arithmetic, divided attention, and risk-taking tasks. Contrary to prediction, females with fragile X rarely exhibited higher arousal than females in either the Turner syndrome or comparison groups. On the Divided Attention Task, both the fragile X and Turner syndrome groups exhibited higher arousal relative to one another based on different physiological indices. Relative to the comparison group, the fragile X group presented with a heightened state of arousal at baseline, based on mean skin conductance range, which may account for little increase in arousal on the cognitive tasks for females with fragile X. Females with Turner syndrome exhibited higher arousal relative to the comparison group on all cognitive tasks, but not for all physiological measures. Factors potentially associated with heightened arousal in fragile X and Turner syndrome are discussed.     

Essential hyperhidrosis in Turner syndrome

We describe two Turner patients suffering from severe essential hyperhidrosis. Since both disorders are rare (1 in 5000 live female births for Turner syndrome and approximately 1 in 1000 persons for essential hyperhidrosis), our finding of two patients with these disorders in a total of 150 essential hyperhidrosis patients may suggest that this association is more frequent in Turner syndrome than previously thought.