Turner Syndrome Patient Research Articles

False aneurysm on distal part of coarctation of the aorta in a parous Turner syndrome patient

False aneurysm associated with untreated coarctation of the aorta (CoA) is an uncommon vascular complication. We present a 41-year-old woman with mosaic Turner syndrome who had CoA complicated with a small false aneurysm on descending aorta just distal to the coarctation. The patient had not been diagnosed with Turner syndrome despite several physical characteristics of the syndrome because she had histories of natural childbirth. The false aneurysm was resected with the coarctation through a thoracotomy and proximal aorta was directly anastomosed to distal aorta. Endovascular therapy has become preferred method in recent years in treatment for coarctation of the aorta. However, careful consideration should be given to the irregularities on the aorta with the coarctation for diagnosis of false aneurysm.

Thrombophilic screening in Turner syndrome.

The aim of this study was to determine, in patients with Turner syndrome (TS), the prevalence of thrombophilic disorders correlating with a higher risk of venous thromboembolism (VTE), to evaluate if thrombophilia is associated with the genetic features of these patients and whether screening before hormone replacement therapy (HRT) is advisable. We examined 82 TS patients. In all patients we analyzed activated factor VIII:C, fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), activated PC resistance, and homocysteine. For every patient, an investigation for mutations in prothrombin G20210A, factor V R506Q, methylenetetrahydropholate reductase (MTHFR) C 677T and A1298C was conducted. Low values of PC in 3 patients (3.70%), low values of PS in 12 (14.81%), and hyperhomocysteinemia in 4 (4.87%) were found; 52 girls (64.2%) presented hyperfibrinogenemia. Three patients were heterozygous for the prothrombin G20210A allele mutation (3.66%) and the factor V mutation was present in 4 patients (4.88%). No TS patient had a homozygous mutation. Mutations in the MTHFR gene were present in 62 girls, in 17 patients (20.7%) they were homozygous and in 45 patients (54.88%) heterozygous. Considering the increased risks with the association between VTE and the higher prevalence of PC and PS deficiencies, TT genotype mutations and high level of fibrinogen, it is advisable to perform a complete thrombophilia screening in TS patients before starting HRT.

Turner Syndrome with Isochromosome Xq and Familial Reciprocal Translocation t(4;16)(p15.2;p13.1)

We present here a 16-year-old Turner syndrome patient with a complex karyotype that includes a maternally-inherited balanced translocation between chromosomes 4 and 16 and mosaicism of the isochromosome Xq10. Her karyotype was 45,X,t(4;16) (p15.2;p13.1)[9]/46,X,i(X) (q10),t(4;16)(p15.2;p13.1) [91]. The karyotype of her father was normal, whereas that of her mother had the same balanced translocation and numerical abnormalities of chromosome X and was designated as 45,X,t(4;16)(p15.2;p13.1) [2]/46,XX,t(4;16)(p15.2;p13.1)[93]/47,XXX,t(4;16) (p15.2; p13.1)[5]. The two siblings of the patient also had the same reciprocal translocation. We consider this to be the first such patient with an inherited reciprocal translocation and structural abnormality of the X chromosome (isochromosome Xq).

Altered Immune Response in Mice Deficient for the G Protein-coupled Receptor GPR34

The X-chromosomal GPR34 gene encodes an orphan G(i) protein-coupled receptor that is highly conserved among vertebrates. To evaluate the physiological relevance of GPR34, we generated a GPR34-deficient mouse line. GPR34-deficient mice were vital, reproduced normally, and showed no gross abnormalities in anatomical, histological, laboratory chemistry, or behavioral investigations under standard housing. Because GPR34 is highly expressed in mononuclear cells of the immune system, mice were specifically tested for altered functions of these cell types. Following immunization with methylated BSA, the number of granulocytes and macrophages in spleens was significantly lower in GPR34-deficient mice as in wild-type mice. GPR34-deficient mice showed significantly increased paw swelling in the delayed type hypersensitivity test and higher pathogen burden in extrapulmonary tissues after pulmonary infection with Cryptococcus neoformans compared with wild-type mice. The findings in delayed type hypersensitivity and infection tests were accompanied by significantly different basal and stimulated TNF-α, GM-CSF, and IFN-γ levels in GPR34-deficient animals. Our data point toward a functional role of GPR34 in the cellular response to immunological challenges.

A SRY-HMG box frame shift mutation inherited from a mosaic father with a mild form of testicular dysgenesis syndrome in Turner syndrome patient

BackgroundSex determining factor (SRY) located on the short arm of the Y chromosome, plays an important role in initiating male sex determination, resulting in development of testicular tissue. Presence of the SRY gene in females results in XY sex reversal and increased risk of gonadal germ cell tumours if the karyotype also includes the so-called GonadoBlastoma on the Y chromosome (GBY) region. The majority of mutations within the SRY gene are de novo affecting only a single individual in the family. The mutations within the high-mobility group (HMG) region have the potential to affect its DNA binding activity.Case PresentationWe performed G- and R-banding cytogenetic analysis of the patient and her family members including her father. We also performed molecular genetic analysis of SRY gene. Cytogenetic analysis in the patient (Turner Syndrome) revealed the mosaic karyotype as 45, X/46, XY (79%/21% respectively) while her father (milder features with testicular dysgenesis syndrome) has a normal male karyotype (46, XY). Using molecular approach, we screened the patient and her father for mutations in the SRY gene. Both patient and her father showed the same deletion of cytosine within HMG box resulting in frame shift mutation (L94fsX180), the father in a mosaic pattern. Histological examination of the gonads from the patient revealed the presence of gonadoblastoma formation, while the father presented with oligoasthenozoospermia and a testicular seminoma. The frameshift mutation at this codon is novel, and may result in a mutated SRY protein.ConclusionOur results suggest that lack of a second sex chromosome in majority cells of the patient may have triggered the short stature and primary infertility, and the mutated SRY protein may be associated with the development of gonadoblastoma. It is of importance to note that mosaic patients without a SRY mutation also have a risk for malignant germ cell tumors.

Hyperfibrinogenemia and prolonged clotting times in a Turner syndrome patient with hepatocellular carcinoma

Here, we diagnosed a Turner syndrome patient complicated with well differentiated hepatocellular carcinoma. The patient had an extremely high level of plasma fibrinogen. However, her clinical features and coagulation test abnormalities were quite different from those reported cases. We investigated the mechanisms underlying the hyperfibrinogenemia and its effects on coagulation tests. Plasma fibrinogen was analyzed by Clauss, immunoturbidimetry and Western methods. The fibrinogen genes were sequenced. Activated partial thromboplastin time, prothrombin time and thrombin time were measured. Fibrinogen expression in tumor tissues was examined immunohistochemically. Plasma cortisone, interleukin 6 and soluble tissue factor were measured by immunoassays. We found that abundant fibrinogen protein was detected in tumor cells. Plasma fibrinogen activity and antigen were 14.4 +/- 0.8 and 15.1 +/- 0.3 g/l, respectively. On SDS-PAGE, patient and control fibrinogen subunits migrated similarly. No mutations were found in the fibrinogen genes. Activated partial thromboplastin time, prothrombin time and thrombin time were significantly prolonged, but were normalized when fibrinogen was partially absorbed by an antifibrinogen antibody. Plasma interleukin 6, cortisone and soluble tissue factor levels were increased as compared with those of controls. After tumor resection, plasma fibrinogen level and other laboratory tests returned to normal. Our results showed that the hyperfibrinogenemia was caused by hepatocellular carcinoma. High levels of plasma cortisone and interleukin 6 may also contribute to the hyperfibrinogenemia. With the increase of levels of plasma fibrinogen, the values of activated partial thromboplastin time, prothrombin time and thrombin time were gradually prolonged, probably due to the effect of fibrin on thrombin (antithrombin I) and restricted fibrin polymerization by superfluous fibrinogen.

A small supernumerary marker chromosome present in a Turner syndrome patient not derived from X- or Y-chromosome: a case report

BackgroundSmall supernumerary marker chromosomes (sSMC) can be present in numerically abnormal karyotypes like in a 'Turner-syndrome karyotype' mos 45,X/46,X,+mar.ResultsHere we report the first case of an sSMC found in Turner syndrome karyotypes (sSMCT) derived from chromosome 14 in a Turner syndrome patient. According to cytogenetic and molecular cytogenetic characterization the karyotype was 46,X,+del(14)(q11.1). The present case is the third Turner syndrome case with an sSMCT not derived from the X- or the Y-chromosome.ConclusionMore comprehensive characterization of such sSMCT might identify them to be more frequent than only ~0.6% in Turner syndrome cases according to available data.

Y-chromosome markers in Turner syndrome: Screening of 130 patients

The presence of Y-chromosome material in patients with Turner syndrome (TS) is a risk factor for the development of gonadoblastoma. Cytogenetic analysis detects Y-chromosome mosaicism in about 5% of Turner patients. However, if Y-chromosome sequences are present in only a few cells, they may be missed by routine analysis. The use of molecular techniques to detect the presence of Y-chromosome fragments in such patients is becoming increasingly important. The objective of our study was to analyze cryptic Y-chromosome derivatives in Hungarian TS patient population by real-time PCR (RT-PCR). Cytogenetic and RT-PCR methods were used to examine peripheral blood DNA of 130 Hungarian patients with TS for the presence of Y-chromosome. With RT-PCR, 4 regions throughout the Y-chromosome were analyzed. Initial cytogenetic karyotyping assessing 10-50 metaphases revealed 3 patients with Y-chromosome positivity. RT-PCR revealed further 6 patients with Y-chromosome, who were initially considered as Y-negatives by standard kayotyping. The consecutive cytogenetic analysis of a large number (about 100) of metaphases (in 5 patients) and/or FISH (in 6 patients) however, also confirmed the presence of the Y-chromosome in these patients. Prophylactic gonadectomy was carried out in all 9 patients and 1 of them was diagnosed as having bilateral gonadoblastoma without clinical symptoms. We recommend a routine molecular screening for hidden Y-chromosome sequences in Turner patients, who are negative for Y-chromosome by conventional cytogenetic analysis, in order to calculate the future risk of developing gonadoblastoma.

X/XY Chromosome Mosaicism: Turner Syndrome and Other Clinical Conditions

X/XY Chromosome Mosaicism: Turner Syndrome and Other Clinical Conditions The 45,X/46,XY mosaicism shows a wide spectrum of phenotypes ranging from females with Turner syndrome, male or female pseudohermaphroditism, to appearently normal male development. Chromosome anomalies accompanying Turner syndrome were found in lymphocyte cultures of 236 patients. Chromosomal analysis revealed the karyotype 45,X in 118 (50.0%) patients. X monosomy mosaics or structural rearrangements of the X chromosome was established in 112 (47.5%) patients. The Y chromosome was found in six (2.5%) patients with typical features of Turner syndrome. In five mosaics 45,X/46,XY the proportion of the XY clone ranged from 46% to 76%. In one Turner syndrome patient only 47,XYY cells were found (solely blood culture investigated). In most cases of 45,X/46,XY mosaicism, the cause is considered to be the loss of the Y chromosome because of nondisjunction after normal disomic fertilisation. Five other patients with X/XY chromosome mosaicism showed mixed gonadal dysgenesis (two patients), one male pseudohermafroditism, one male with Pierre Robin syndrome, and one normal male phenotype. In two non Turner syndrome patients nondisjunction of the primary clone 46,XY was obvious and resulted in mosaicism 45,X/46,XY/47,XYY, the one patient contained dicentric Y. The similarities between X/XY Turner syndrome and other nosological entity of females possessing Y chromosome — the Swyer syndrome — are discussed.

Poor outcome in oocyte donation after elective transfer of a single cleavage-stage embryo in Turner syndrome patients

In this retrospective, matched study we evaluated the outcome of 31 oocyte donation (OD) cycles performed in 29 Turner syndrome (TS) patients involving the elective transfer of a single, fresh cleavage-stage (day 2 to 3) embryo. Due to the fact that ongoing pregnancy rate was statistically significantly lower (3.2% versus 22.5%) in TS patients when compared with matched, non-TS recipients, other strategies (such as single blastocyst transfer) should be evaluated that could enable better outcomes and at the same time avoid potential complications related to multiple pregnancies in this particularly high obstetric-risk group.

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG

Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6+/-3.1 vs. 11.8+/-2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, p<0.05, respectively). We conclude that exercise testing and 24-h ECG recording provide valuable information about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking.

Non‐chromosome 11‐p syndromes in Wilms tumor patients: Clinical and cytogenetic report of two Down syndrome cases and one Turner syndrome case

Non‐chromosome 11‐p syndromes in Wilms tumor patients: Clinical and cytogenetic report of two Down syndrome cases and one Turner syndrome case

Lack of meiotic crossovers during oogenesis in an apparent 45,X Ullrich–Turner syndrome patient with three children

A woman with apparent 45,X Ullrich-Turner syndrome was ascertained after the birth of three girls, the last being growth retarded due to a del(X)(p22.11) of grand-paternal origin. In this woman no del(X)-chromosome was detectable in blood by FISH or PCR. Fibroblast cultures from four different biopsies of her skin varied from having 45,X only to mosaic 46,X,del(X) to 46,X,del(X) only. In one fibroblast culture, a few cells with two del(X) chromosomes were found, probably remnants of a paternal dicentric X that caused the condition. Her three daughters were born when she was 29, 31, and 39 years old, respectively, indicating that disomy for the distal half of Xp is not required for normal folliculogenesis. When studying the crossover pattern of her daughters' maternal X-chromosomes, it turned out that one daughter had an X that was exclusively grand-maternal, one daughter lacked crossovers on Xq, and one daughter lacked crossovers on Xp. This suggests that univalent X-chromosomes were present in the Ullrich-Turner patient's primordial egg cells, either because there was only a single X-chromosome present (a 45,X primary oocyte), or because the X-chromosome was a partially or completely unpaired in pachytene, indicating a problem with chromosome association and synapsis formation.

Identification of Y-chromosome by Molecular Analysis in Patients with Turner Syndrome

It is known that the Y chromosome or Y-specific sequence is present in about 6% of Turner syndrome (TS) patients and that it predisposes them to gonadoblastoma formation with an estimated risk of 15-25%. In this study, we performed a polymerase chain reaction (PCR) in 32 patients with TS to detect Y-specific sequence. The results were compared with those obtained by the fluorescence in situ hybridaization (FISH) method. Cytogenetic analysis was performed by phytohaemagglutinin (PHA)-stimulated peripheral lymphocyte cultures, using G-banding. DNA was extracted from peripheral blood for PCR. Seven different sets of oligonucleotide primers, sex determining region Y (SRY), zinc finger gene on the Y chromosome (ZFY), testis specific protein Y (TSPY), DYZ3, DYF49S1, RNA binding motif protein (RBM), and DYZ1, spanning on centromeres and short and long arms of the Y chromosome were used for PCR. FISH was carried out using X and Y chromosome enumeration probe for Xp11.1-q11.1 (DXZ1 locus) and Yp11.1-q11.1 (DYZ3 locus), respectively. Among 32 patients with TS, four (12.5%) were positive for Y specific sequence by PCR. Of these, two patients were detected previously by a cytogenetic analysis: 45,X/47,XYY and 45,X/46,XY. Only one Y specific sequence, DYZ3, was detected by PCR in the other two patients without cytogenetically obvious Y chromosome. Y signal was not detected by FISH for the last two patients. It may be reasonable to consider using a PCR method to screen for Y-specific sequences in all patients with TS. Even though we did not demonstrate Y-signal by FISH in patients with PCR positive and cytogenetically no obvious Y chromosome, FISH may be another useful method in TS patient, and futher investigation is nessessary.

Rhabdoid meningioma of the tentorium with expression of desmin in a 12-year-old Turner syndrome patient

Rhabdoid meningioma (RM) is a histological subtype of meningioma, associated with aggressive behaviour, characterized by patches or sheets of rhabdoid cells [2, 3, 4], similar to renal and extra-renal rhabdoid tumours [1, 7] and atypical teratoid/rhabdoid tumour (AT/RT) [6]. A RM with expression of desmin in the tentorium of a 12-year-old female, is described. To the best of our knowledge, this is the first case in a Turner syndrome patient. Clinical history consisted of several months of headache and right arm weakness. Neurological examination revealed right-sided hypotonia and hypostenia, tremor, imbalance, and ataxic gait. Physical examination showed short stature and delayed sexual development. On the basis of karyotype analysis, Turner syndrome was diagnosed. Computed tomography demonstrated a hyperdense mass in close relationship with the right cerebellar hemisphere, compressing the fourth ventricle. Magnetic resonance imaging (MRI) (Fig. 1a) demonstrated a T1 isointense, T2 hypointense tumour of the tentorium with extra-axial extension, both caudally and cranially. A ‘dural tail’ was seen medially. Necrotic portions were persistently hypointense after gadolinium administration. No brain or spinal metastasis were observed. The patient underwent a parieto-occipital craniotomy. The tumour was located in the posterior fossa, arising from the dura of the inferior surface of the tentorium, and extending into the supratentorial region. As the tumour was attached to the transverse sinus, only a subtotal resection was achievable. A minimal residual tumour, not demonstrated by post-operative neuroimaging, was left. Abdominal ultrasonography and chest X-ray were normal. After diagnosis the patient received local radiotherapy and hydroxyurea chemotherapy. MRI at 20 months was negative. Microscopic examination disclosed a highly cellular tumour entirely composed of sheets of large oval cells with eosinophilic cytoplasm, containing globular eosinophilic inclusions, and eccentric nuclei. Mitotic index was high (12/10 high-power field) (Fig. 1b). Multiple foci of necrosis were seen. Meningothelial lobules, whorls, and psammoma bodies were absent. Brain invasion was not observed. Tumour cells showed strong immunoreactivity for vimentin and focal membrane staining for epithelial membrane antigen (EMA) (Fig. 1c); the inclusions were immunoreactive for desmin (Fig. 1d). Tumour cells were negative for smooth muscle actin, muscle specific actin, MyoD1, myogenin, S-100 protein, and CD34. MIB1 labelling index was 15%. The coding sequences of hSNF5/INI1 and NF2 genes were screened by single-strand conformation polymorphism. The microsatellite markers (D22S1685D22S1553) on 22q11.23, near the hSNF5/INI1 locus, were analysed. No aberrant migration pattern of INI1 gene or loss of heterozygosity of INI1 locus were found. A deletion of exon 9 of the NF2 gene was detected. The first two authors contributed equally.

Acute motor axonal neuropathy in a Turner's syndrome patient with a ‘potential’ celiac disease

Acute motor axonal neuropathy in a Turner's syndrome patient with a ‘potential’ celiac disease

A nonmosaic 45,X karyotype in a mother with Turner's syndrome and in her daughter

To describe a woman with a nonmosaic (45,X) form of Turner's syndrome who gave birth to a girl with 45,X Turner syndrome. Patient report. Outpatient clinic of a university hospital. A woman with typical phenotypic features of Turner syndrome and a 45,X karyotype and her daughter with the same karyotype. None. Routine karyotype analysis on 200 white blood cells on two different occasions, on skin fibroblasts (1,000 mitoses) and on ovarian fibroblasts. Translocation of X-chromosome material was investigated by a complete X paint and fluorescent in situ hybridization analysis. The patient had a spontaneous puberty and became pregnant on three occasions. Her first daughter has a normal karyotype, the second pregnancy ended in spontaneous abortion, and after the third pregnancy, a girl was born with a 45,X karyotype. Karyotype analysis of a large number of mitoses in three different cell types failed to demonstrate any mosaicism. Translocation of X-chromosome material was ruled out by fluorescent in situ hybridization analysis with an X paint. This is a rare case of pregnancy in a nonmosaic Turner syndrome patient and, to our knowledge, is the only one that resulted in a live-born baby with the same karyotype. Cryptic mosaicism could not be found despite thorough investigations. Some hypotheses are presented that may explain this unique event.

Del(X)(p22.1)/r(X)(p22.1q28) dynamic mosaicism in a Turner syndrome patient

We report on a 16-year-old patient with Turner syndrome who presented a mos 46,X,del(X)(p22.1)〚35〛/45,X〚19〛/46,X,r(X)(p22.1q28) 〚6〛 GTG-band karyotype. The R-banding showed that the abnormal X-chromosome was inactive in all 61 cells analyzed. Fluorescence in situ hybridization with a Xp/Yp subtelomeric probe revealed that both abnormal chromosomes lacked the complementary sequences, a fact consistent with a terminal deletion. Besides, the molecular analysis of the human androgen receptor gene showed that the rearranged chromosome was paternal in origin. Since the deleted and the ring chromosomes had the same size and banding pattern, and because the former was the predominant cell line, it was inferred that the Xp– formed a ring in some cells apparently without further loss of genetic material. However, the reverse sequence and even a simultaneous origin due to a complex intrachromosomal exchange are also conceivable. The mild Turner syndrome phenotype is explained by the mosaicism and by the size of the deleted segment.

An unusual case of aortic dissection in Turner's syndrome

Cardiovascular malformations are common in patients with Turner's syndrome. Aortic coarctation and bicuspid aortic valve are the most frequently occurring abnormalities, and are associated with cystic medial necrosis of the aortic wall. Aortic dissection is an uncommon but catastrophic complication of the 'aortopathy' of Turner's syndrome. We report the unusual case of a Turner's syndrome patient (with a bicuspid aortic valve and previous coarctation repair) who died following an intramural haemorrhage of the aortic root that was complicated by dissection and rupture, with no evidence of aortic intimal tear. The role of intramural haemorrhage in the pathogenesis of acute aortic syndromes in Turner's syndrome patients is unclear. The condition may be associated with atypical clinical presentations, it can be difficult to confirm with imaging techniques, and it carries a high risk of progression to classical aortic dissection and death. This case therefore highlights the need for a high index of suspicion when assessing Turner's syndrome patients presenting with chest pain syndromes. Furthermore, the effective management of Turner's syndrome patients with cardiovascular abnormalities requires the development of evidence-based preventive (such as echocardiographic surveillance of aortic dilatation) and interventional strategies.

A case of 45,X Turner syndrome with spontaneous ovulation proven by ultrasonography

A well-documented case of non-mosaic Turner syndrome, with spontaneous pubertal development and ovulatory cycles is reported. Mosaicism could be excluded both by karyotyping of 172 metaphases of blood lymphocytes and fibroblasts, and by fluorescence in situ hybridization, using an X-centromeric probe, in 200 blood lymphocyte nuclei. This Turner syndrome patient underwent normal pubertal development, with spontaneous menarche at 14 years, followed by regular monthly periods. Hormonal measurements performed during puberty were consistent with the patient's pubertal development. At the age of 26 years the patient was referred for complete fertility evaluation. Detailed hormonal analyses were performed in a given cycle. They showed midluteal phase estradiol and progesterone values within the range corresponding to normal ovulation and corpus luteum function. In the same cycle, pelvic ultrasonography was also performed at days 13, 15 and 18. It demonstrated a spontaneous ovulation, with follicular rupture that occurred between days 15 and 18.This is the first report of a spontaneous ovulation in Turner syndrome evidenced, not only by hormonal analysis, but also by ultrasonographic demonstration of follicular rupture.