Stigmata Of Turner Syndrome Research Articles

45,X/46,XY mosaicism: Clinical manifestations and long term follow-up.

45,X/46,XY chromosomal mosaicism presents a range of clinical manifestations, including phenotypes from Turner syndrome through genital abnormalities to apparently unaffected phenotypic males; however, the full clinical spectrum has not yet been fully delineated since prior studies on the clinical phenotype and associated risk of gonadal tumors included small cohorts and limited follow-up. To better describe the clinical manifestations and long-term outcome of patients with 45,X/46,XY mosaicism. We conducted a retrospective chart review of patients with 45,X/46,XY from three health centers (Hospital for Sick Children and Mount Sinai Hospital in Canada, and University of Pittsburgh Medical Center in United States). Of 100 patients with 45,X/46,XY karyotype, 47 were raised as females and 53 as males. Females were significantly shorter than males (p = 0.04) and height Z-score was significantly decreased with age for both genders (p = 0.02). Growth hormone (GH) treatment did not result in a significant height increase compared to the untreated group (p = 0.5). All females required puberty induction in contrast to majority of males. Five females were diagnosed with gonadal tumors, while no males were affected. Around 58% of patients exhibited at least one Turner syndrome stigmata. This study expands the clinical spectrum, long-term outcomes, and associated tumor risk in a large cohort of patients with 45,X/46,XY mosaicism. Additionally, it highlights our experience with GH therapy and prophylactic gonadectomy.

SAT-300 Role of Adrenal Progesterone in the Maturation of the Endometrial Lining and Regulation of Menses in Turner Syndrome

Background: In Turner syndrome (TS) with primary ovarian failure (POF), low-dose estrogen (E) therapy (tx) is started at 11-12 years of age, with dose increments over 2-3 years. Progesterone (P) is added once breakthrough bleeding occurs or after 2 years of E tx. Irregular bleeding can occur from unopposed E but both exogenous E and P are necessary for regular menses. In POF, the only source of endogenous P is adrenal. Adrenal steroidogenesis has been postulated to play a role in P increase during the menstrual cycle [1], and LH receptors have been found in the adrenal cortex [2]. In ovariectomized rats, E tx has been found to increase adrenal activity [3]. Objective: To study the effect of endogenous adrenal P on endometrial lining and regulating menses in a case of TS with POF. Clinical Case: An adolescent girl with TS (45X) was diagnosed with POF at 1 month of age (FSH 65.66 U/L, LH 8.31 U/L). At 12 yrs, besides TS stigmata, she had prepubertal breasts and sparse, thin pubic hair with high FSH 88.2 U/L and LH 20.13 U/L. Pubertal induction with transdermal estradiol (TDE) patch was started at 6.25 mcg 2x/wk with dose increments up to 25 mcg 2x/wk over 2 years. At 14.2 yrs, she had Tanner 3 breasts and pubic hair and had menarche. She had 3 irregular periods over the next 6 months with intervals of 1-3 months. At 14.8 years, menses started occurring regularly only on exogenous TDE (FSH 11.3 U/L, LH 5.92 U/L, E 37 pg/mL). Each period would last 3 to 4 days w/ regular flow. At 15 yrs, weekly serum P on day 15 post-LMP showed consistently detectable levels of 0.5, 0.6, 0.7, and 0.6 ng/mL respectively (ref for follicular phase: 0.15-1.4 ng/mL). ACTH stim test showed increase in serum cortisol from 5.2 to 28.5 mcg/dL and serum P from 0.27 to 1.68 ng/mL at 60 mins. US showed uterine size 5.7x1.8x3.5cm and endometrial stripe 11 mm, implying that perhaps the P level was enough to maintain her endometrial lining (day 20 post-LMP). Menses continued at regular intervals of 22-43 days for 12 months on TDE without P replacement. Most recent LH 4.33 U/L, FSH 10.5 U/L, E 67 pg/mL, P 0.64 ng/mL, DHEAS 162 ug/dL. AMH was <0.015 ng/mL and inhibin B <10 pg/mL, consistent with no ovarian function. Conclusion: Although extremely rare, patients with POF may develop regular menses on estrogen therapy without progesterone replacement. Adrenal progesterone may assist in the maturation of the endometrial lining and regulation of menses. 1. De Geyter, C., et al., Progesterone serum levels during the follicular phase of the menstrual cycle originate from the crosstalk between the ovaries and the adrenal cortex. Hum Reprod, 2002. 17(4): p. 933-9. 2. Pabon, J.E., et al., Novel presence of luteinizing hormone/chorionic gonadotropin receptors in human adrenal glands. J Clin Endocrinol Metab, 1996. 81(6): p. 2397-400. 3. Saruhan, B.G. and N. Ozdemir, Effect of ovariectomy and of estrogen treatment on the adrenal gland and body weight in rats. Saudi Med J, 2005. 26(11): p. 1705-9.

SSMC Characterization in a Male with Turner Syndrome Stigmata

Background: Small supernumerary marker chromosomes (sSMC) are rare cytogenetic findings in general, but especially in Turner syndrome so called sSMCT in a karyotype 46,X,mar are even more scarce. According to the literature sSMCT are derived from one of the Y-chromosome in ~70% of the cases. Thus, to identify potentially present Y-chromosomal material cases is imperative, since these cases have an increased risk of gonadoblastoma deriving from the streak gonads. Methods: A 24-year-old short statured male presented with ambiguous genitalia, undescended testicles and elevated serum testosterone level. Karyotyping and an SRY-gene specific polymerase chain reaction (SRY-PCR) test were done. After detection of the sSMCT in metaphase directed fluorescence in situ hybridization (FISH), sex-chromosome-specific microsatellite analysis and interphase-FISH were additionally applied. Results: In initial cytogenetic analyses the patient’s karyotype was reported as 45,X[10]; however, presence of SRY-sequences was detected by in parallel performed SRY-PCR analyses of peripheral blood. Applying FISH, a karyotype of mos 46,X,der(Y)(:p11.2->q11.1:)[7]/45,X[13] was found. However, according to microsatellite analysis using gonosome specific markers indicated for the presence of SRY in Yp11.31 and sY84 in Yq11.21, as well. Finally, interphase FISH revealed the presence of the SRY-region in ~8% of the cells. Thus, the final karyotype was defined as: mos 46,X,der(Y)(pter->p11.31::p11.2->q11.1:)[19]/46,X,der(Y)(:p11.2->q11.1:)[32]/45,X[189]. Conclusion: In the here presented sSMCT case stepwise diagnostics, using sequentially molecular cytogenetic and molecular genetic tests was necessary to finally characterize the genetic condition comprehensively. Overall, subsequent correct clinical management could now be given.

Gonadoblastoma with Dysgerminoma in a Phenotypically Turner-Like Girl with 45,X/46,XY Karyotype

Individuals with 45,X/46,XY karyotype are at increased risk for germ cell tumor development. We report a case with a diagnosis of 45,X/46,XY gonadal dysgenesis who presented with short stature, physical stigmata of Turner syndrome. Her pubertal development was at Tanner stage 3. At follow-up, bilateral prophylactic gonadectomy was performed when considering the risk factors. Pathological assessment was consistent with gonadoblastoma in the left gonad, and dysgerminoma and gonadoblastoma in neighboring areas in the right gonad. The karyotype analysis of the right and left gonadal tissues reveled 45,X[97,3]/46,XY[2,7] and 45,X[92,7]/46,XY[4,5]/47,XYY [2,8] mosaic, respectively. The clinical management of such patient should be individualized according to the present risk factors. Additionally, signs of estrogenization like advanced breast development always suggest the possible presence of germ cell tumor.

Genomic profile of a Li-Fraumeni-like syndrome patient with a 45,X/46,XX karyotype, presenting neither mutations in TP53 nor clinical stigmata of Turner syndrome

Li-Fraumeni syndrome (LFS) is a hereditary disorder that predisposes patients to several types of cancer and is associated with TP53 germline mutations. Turner syndrome (TS) is one of the most common aneuploidies in women. Patients with TS have a higher risk of developing cancer, although multiple malignant tumors are extremely rare. Herein, we describe a patient with a 45,X/46,XX karyotype with no classic phenotype of TS. She presented with a clinical diagnosis of Li-Fraumeni-like syndrome (LFL), showing papillary thyroid carcinoma and fibrosarcoma of the left flank, and had no TP53 germline mutations. Genome-wide analysis of copy number variations (CNVs) was assessed in DNA from peripheral blood cells and saliva. A total of 109 rare CNVs in the blood cells, including mosaic loss of the X chromosome (76% of cells), were identified. In saliva, three rare CNVs were detected, all of them were also detected in the blood cells: loss of 8q24.11 (EXT1), gain of 16q24.3 (PRDM7 and GAS8), and the mosaic loss of the X chromosome (50% of cells). Results of conventional G-banding confirmed the 45,X/46,XX karyotype. Surprisingly, the patient presented with an apparently normal phenotype. The PRDM and GAS8 genes are potential candidates to be associated with the risk of developing cancer in this LFL/TS patient.

Analysis of Turner Syndrome Patients within the Jordanian Population, with a Focus on Four Patients with Y Chromosome Abnormalities

This study presents findings in Turner syndrome (TS) patients from the Jordanian population, with focus on 4 patients with Y chromosomal abnormalities. From 1989 to 2011, 504 patients with TS stigmata were referred to our institute for karyotyping, resulting in 142 positive TS cases. Of these, 62 (43.7%) had the typical 45,X karyotype and the remaining individuals (56.3%) were found to be mosaics. Fifteen TS patients (10.5%) carried a structural abnormality of the Y chromosome and presented with the mosaic 45,X/46,XY karyotype. From these, 4 TS cases were investigated further. Karyotyping revealed that 1 patient carried a small supernumerary marker chromosome, whereas cytogenetic and molecular analyses showed that 3 patients carried 2 copies of the SRY gene. Further analysis by SRY sequencing revealed no mutations within the gene. The analyzed patients were found to be phenotypically either females or males, depending on the predominance of the cell line carrying the Y chromosome. This study demonstrates the importance of detailed cytogenetic analysis (such as FISH) in TS patients, and it also emphasizes the need for molecular analysis (such as PCR and sequencing) when fragments of the Y chromosome are present.

Neocentric X-chromosome in a girl with Turner-like syndrome

BackgroundNeocentromeres are rare human chromosomal aberrations in which a new centromere has formed in a previously non-centromeric location. We report the finding of a structurally abnormal X chromosome with a neocentromere in a 15-year-old girl with clinical features suggestive of Turner syndrome, including short stature and primary amenorrhea.ResultG-banded chromosome analysis revealed a mosaic female karyotype involving two abnormal cell lines. One cell line (84% of analyzed metaphases) had a structurally abnormal X chromosome (duplication of the long arm and deletion of the short arm) and a normal X chromosome. The other cell line (16% of cells) exhibited monosomy X. C-banding studies were negative for the abnormal X chromosome. FISH analysis revealed lack of hybridization of the abnormal X chromosome with both the X centromere-specific probe and the “all human centromeres” probe, a pattern consistent with lack of the X chromosome endogenous centromere. A FISH study using an XIST gene probe revealed the presence of two XIST genes, one on each long arm of the iso(Xq), required for inactivation of the abnormal X chromosome. R-banding also demonstrated inactivation of the abnormal X chromosome. An assay for centromeric protein C (CENP-C) was positive on both the normal and the abnormal X chromosomes. The position of CENP-C in the abnormal X chromosome defined a neocentromere, which explains its mitotic stability. The karyotype is thus designated as 46,X,neo(X)(qter- > q12::q12- > q21.2- > neo- > q21.2- > qter)[42]/45,X[8], which is consistent with stigmata of Turner syndrome. The mother of this patient has a normal karyotype; however, the father was not available for study.ConclusionTo our knowledge, this is the first case of mosaic Turner syndrome involving an analphoid iso(Xq) chromosome with a proven neocentromere among 90 previously described cases with a proven neocentromere.

45,X/46,XY mosaicisme: Report of five cases and clinical review

Introduction The mosaicism 45, X/46, XY is a gonosomal abnormality characterized by a broad phenotypic spectrum, ranging from women with or without Turner syndrome stigmata, to men apparently normal, passing by the ambiguous phenotypes with variable virilisation of external genitalia. From the histological point of view, several situations may arise. Patients and methods We analyzed the clinical, hormonal, sonographic, and genitographics data, as well as peroperative and histological findings for five cases of mosaicism 45, X/46, XY, and we discussed treatment performed. Results The mean age of patients was 6.6 years, two had a female phenotype with clitoral hypertrophy (one of them had Turner syndrome stigmata), one had a normal male phenotype with bilateral cryptorchidism and two had an ambiguity of external genitalia assigned to male. Short stature was noted for four patients. Surgical exploration concluded to the diagnosis of mixed gonadal dysgenesis for four of our patients. No cases of gonadoblastoma have been reported, for girls a prophylactic gonadectomy was performed, for boys the streak gonad was resected and the dysgenetic testis biopsied and preserved, subject for constant monitoring. Conclusion This heterogeneity indicate the importance of an accurate clinical and histological evaluation of any patient presenting with 45, X/46,XY mosaicism.

X-autosomal translocation — a distraction or a cause of primary ovarian insufficiency?

OBJECTIVE: To characterize the genetic basis of primary ovarian insufficiency (POI) in a patient with a balanced X-autosomal translocation involving one X chromosome and a deletion at Xq27.2 on the other X chromosome. X-autosomal translocations have been associated with POI, possibly due to aberrations in pairing or X inactivation during folliculogenesis. Additionally, the putative genes leading to POI are located at one of two loci on Xq: POF1 (Xq26-q28) or POF2 (Xq13.3-q22), with the minimal POF1 deletion associated with POI narrowed to a 10.5 Mb region at Xq27.2/Xq27.3-q28.DESIGN: Case report.MATERIALS AND METHODS: 23 year-old with oligomenorrhea and primary infertility. She reported menarche at age 13. After discontinuation of oral contraceptive pills at age 22, she experienced oligomenorrhea and infertility. There was no family history of POI. Her physical exam was unremarkable and showed no stigmata of Turner Syndrome. Relevant laboratory data included: day 3 FSH=61.2 mIU/mL, day 3 estradiol <20 pg/mL and normal FMR1 premutation testing.RESULTS: Standard karyotype testing (GTG band resolution 550) revealed 46,X,t(X;1)(q22.1;q42.1), indicating a balanced translocation involving chromosomes X and 1, with no apparent macroscopic loss of genetic material from the translocated chromosomes. Subsequent microarray comparative genomic hybridization (NimbleGen CGX-3 array) revealed a cryptic 382-482 kb deletion at Xq27.2 (arr Xq27.2(140,201,306-140,583,606)x1). In order to confirm the microarray findings and localize the deletion, fluorescence in situ hybridization (FISH) analysis was performed with a BAC probe (RP11-1082H4) mapping to the deleted region. The deletion was present on the X chromosome that was not involved in the translocation.CONCLUSION: Our patient exhibits a balanced X-autosomal translocation, which has been associated with POI, but appears to be an incidental finding in this patient. This case further narrows the minimal POF1 deletion associated with POI to a 382-482 kb deletion at Xq27.2. OBJECTIVE: To characterize the genetic basis of primary ovarian insufficiency (POI) in a patient with a balanced X-autosomal translocation involving one X chromosome and a deletion at Xq27.2 on the other X chromosome. X-autosomal translocations have been associated with POI, possibly due to aberrations in pairing or X inactivation during folliculogenesis. Additionally, the putative genes leading to POI are located at one of two loci on Xq: POF1 (Xq26-q28) or POF2 (Xq13.3-q22), with the minimal POF1 deletion associated with POI narrowed to a 10.5 Mb region at Xq27.2/Xq27.3-q28. DESIGN: Case report. MATERIALS AND METHODS: 23 year-old with oligomenorrhea and primary infertility. She reported menarche at age 13. After discontinuation of oral contraceptive pills at age 22, she experienced oligomenorrhea and infertility. There was no family history of POI. Her physical exam was unremarkable and showed no stigmata of Turner Syndrome. Relevant laboratory data included: day 3 FSH=61.2 mIU/mL, day 3 estradiol <20 pg/mL and normal FMR1 premutation testing. RESULTS: Standard karyotype testing (GTG band resolution 550) revealed 46,X,t(X;1)(q22.1;q42.1), indicating a balanced translocation involving chromosomes X and 1, with no apparent macroscopic loss of genetic material from the translocated chromosomes. Subsequent microarray comparative genomic hybridization (NimbleGen CGX-3 array) revealed a cryptic 382-482 kb deletion at Xq27.2 (arr Xq27.2(140,201,306-140,583,606)x1). In order to confirm the microarray findings and localize the deletion, fluorescence in situ hybridization (FISH) analysis was performed with a BAC probe (RP11-1082H4) mapping to the deleted region. The deletion was present on the X chromosome that was not involved in the translocation. CONCLUSION: Our patient exhibits a balanced X-autosomal translocation, which has been associated with POI, but appears to be an incidental finding in this patient. This case further narrows the minimal POF1 deletion associated with POI to a 382-482 kb deletion at Xq27.2.

Turner syndrome and its variants

Case records of female patients with karyotype proven turner syndrome were analyzed. 11 patients had classic Turner karyotype (Group 1) and 13 patients had karyotype suggestive of one of the variants of Turner syndrome (Group 2). There was a median difference of 3 years between the age of presentation and the age of diagnosis in Group 2. Out of the thirteen patients in Group 2, 4 had no clinical stigmata of Turner Syndrome; the rest (n=9) had one or more of the typical clinical stigmata of Turner Syndrome. One patient with a complex mosaic karyotype also had an intracranial medulloblastoma. One patient in each group had coarctation of the aorta. 5 patients in Group 1 and 3 patients in Group 2 had primary hypothyroidism and received levothyroxine. The median Thyroid Stimulating Hormone levels were significantly higher among patients in group 1 than in group 2.

Long-term Growth Hormone Therapy in an Adolescent Boy with 45,X/46,XidicY(p11)

A 17-year-old boy with chromosomal mosaicism resulting in a 45,X/46,X,idic(Y)(p11) karyotype came to medical attention at the age of 10 years because of short stature. He was treated with recombinant growth hormone for 6.6 years and has achieved a near final adult height of 172.5 cm. His clinical features included second-degree hypospadias, some stigmata of Turner syndrome, and spontaneous progression through puberty. We report long-term use of growth hormone in a male adolescent with isodicentric Yq.

Anomalies de structure du chromosome Y et syndrome de Turner

Although specifically male, the human Y chromosome may be observed in female karyotypes, mostly in women with Turner syndrome stigmata. In women with isolated gonadal dysgenesis but otherwise normal stature, the testis determining factor or SRY gene may have been removed from the Y chromosome or may be mutated. In other women with Turner syndrome, the karyotype is usually abnormal and shows a frequent 45,X/46,XY mosaicism. In these cases, the phenotype depends on the ratio between Y positive and 45,X cell lines in the body. When in mosaicism, Y chromosomes are likely to carry structural abnormalities which explain mitotic instability, such as the existence of two centromeres. Dicentric Y isochromosomes for the short arm (idic[Yp]) or ring Y chromosomes (r[Y]) are the most frequent abnormal Y chromosomes found in infertile patients and in Turner syndrome in mosaic with 45,X cells. Although monocentric, deleted Y chromosomes for the long arm and those carrying microdeletions in the AZF region are also instable and are frequently associated with a 45,X cell line. Management of infertile patients carrying such abnormal Y chromosomes must take into account the risk and the consequences of a mosaicism in the offspring.

Cryptic mosaicism involving a second chromosome X in patients with Turner syndrome

The high abortion rate of 45,X embryos indicates that patients with Turner syndrome and 45,X karyotype could be mosaics, in at least one phase of embryo development or cellular lineage, due to the need for the other sex chromosome presence for conceptus to be compatible with life. In cases of structural chromosomal aberrations or hidden mosaicism, conventional cytogenetic techniques can be ineffective and molecular investigation is indicated. Two hundred and fifty patients with Turner syndrome stigmata were studied and 36 who had female genitalia and had been cytogenetically diagnosed as having "pure" 45,X karyotype were selected after 100 metaphases were analyzed in order to exclude mosaicism and the presence of genomic Y-specific sequences (SRY, TSPY, and DAZ) was excluded by PCR. Genomic DNA was extracted from peripheral blood and screened by the human androgen receptor (HUMARA) assay. The HUMARA gene has a polymorphic CAG repeat and, in the presence of a second chromosome with a different HUMARA allele, a second band will be amplified by PCR. Additionally, the CAG repeats contain two methylation-sensitive HpaII enzyme restriction sites, which can be used to verify skewed inactivation. Twenty-five percent (9/36) of the cases showed a cryptic mosaicism involving a second X and approximately 14% (5/36), or 55% (5/9) of the patients with cryptic mosaicism, also presented skewed inactivation. The laboratory identification of the second X chromosome and its inactivation pattern are important for the clinical management (hormone replacement therapy, and inclusion in an oocyte donation program) and prognostic counseling of patients with Turner syndrome.

Girl With Partial Turner Syndrome and Absence Epilepsy

This report describes a 16-year-old girl with short stature (-5 standard deviations), normal puberty, panic attacks, absence epilepsy, some stigmata of Turner syndrome, and a Madelung deformity. Routine chromosomal analysis revealed a female karyotype with one abnormal chromosome X, with the suspicion of additional material on the short arm. With fluorescent in situ hybridization and array-multiplex amplifiable probe hybridization methodology, a complex aberration was detected, with a deletion of the distal part of Xp22.33 (including the short-stature homeobox gene) and a duplication of Xp22.32-p22.12 proximal to the deleted segment. The deletion in our patient involves the Xp22.33 region. Two genes in this region may contribute to the patient's phenotype: short-stature homeobox, and visuospatial/perceptual abilities. The duplication in our patient involves the Xp22.12-p22.32 region, which, according to the Online Mendelian Inheritance in Man database, contains at least 93 genes, 49 of which are of unknown function. It is difficult to conjecture which gene overexpression in this region may have contributed to the phenotype of our patient. To our knowledge, this small, complex chromosome X aberration was not described previously.

Kabuki syndrome in a girl with mosaic 45,X/47,XXX and aortic coarctation

To describe the clinical findings of a patient with mosaic 45,X/47,XXX and aortic coarctation. Descriptive case study. Tertiary medical center. A 6-year-old girl with stigmata of Turner syndrome, aortic coarctation, patent ductus arteriosus, and a peculiar facial appearance. None. Cytogenetic analysis. The patient manifested a characteristic Kabuki syndrome facial appearance with long palpebral fissures, everted lateral third of lower eyelids, arched eyebrows, a depressed nasal tip, large dysplastic ears and epicanthic folds. She had undergone cardiac surgery for treatment of aortic coarctation and patent ductus arteriosus. Cytogenetic analysis of the blood lymphocytes revealed a karyotype of mos 45,X,9ph [35 cells]/47,XXX,9ph [5 cells]. This is the first report of mosaic 45,X/47,XXX associated with Kabuki syndrome. We emphasize that Kabuki syndrome, a peculiar facial appearance and aortic coarctation, should be considered in girls with sex chromosome abnormalities.

Turner syndrome: counseling prior to oocyte donation.

Ovarian failure is a typical feature of Turner syndrome (TS). Patients are followed clinically with hormone replacement therapy (HRT) and inclusion in the oocyte donation program, if necessary. For patients with spontaneous puberty, genetic counseling regarding preimplantation genetic diagnosis and prenatal diagnosis is indicated. Patients with dysgenetic gonads and a Y chromosome are at increased risk of developing gonadoblastoma. Even though this is not an invasive tumor, its frequent association with other malignant forms justifies prophylactic gonadectomy. It is important to perform gonadectomy before HRT and pregnancy with oocyte donation. Among patients with TS stigmata and female genitalia, many have the Y chromosome in one of the cell lines. For this reason, all patients should undergo cytogenetic analysis. Nevertheless, in cases of structural chromosomal alterations or hidden mosaicism, the conventional cytogenetic techniques may be ineffective and molecular investigation is indicated. The author proposes a practical approach for investigating women with TS stigmata in whom identification of the X or Y chromosome is important for clinical management and follow-up.

Seminoma and a gonadoblastoma in an infant with mixed gonadal dysgenesis

The genital examination of a newborn with ambiguous genitaliarevealedanenlargedphallicstructure,asingleanterior perineal opening, and fused labioscrotal folds with no palpable gonads (Fig 1). No Turner syndrome stigmata were present. The testosterone level was 29 ng/dL (normal range for female newborns, 20-64 ng/dL; males, 75-400 ng/dL), and a mullerian inhibitory substance was undetectable. Chromosome analysis revealed a 45,X/46,XY mosaic karyotype. A normal uterus and kidneys were identified by ultrasonogram, and a urogenital sinus was present on cystourethrogram. The family selected a female gender for the baby. At9monthsofage,theinfanthadbilateralgonadectomy and feminizing genital surgery. Intraoperative findings confirmed a low confluence urogenital sinus with a well-formed vagina. A streak gonad with a normal fallopian tube and hemiuterus were present on the right. The left gonad was torsed and free-floating in the abdomen without identifiable ductal structures. Pathologic examination of the right gonad showed a testis-streak with seminiferous tubules containing placental alkaline phosphatase-positive (PLAP) cells, consistent with intratubular germ cell neoplasia, and peripheral streak gonadal tissue with multifocal areas of gonadoblastoma (Fig 2, B). The left gonad consisted of an encapsulated 2.0 3 1.8 3 0.6 cm soft tissue mass with diffuse coagulative necrosis and dystrophic calcifications consistent with torsion. Sheets of monomorphic large round cells surrounded by fibrous septae (Fig 2, A) were identified, consistent with a seminoma. A computed tomography scan of the abdomen, pelvis, and chest showed no evidence of metastasis. Beta-human chorionic gonadatropin and a-fetoprotein levels were normal. We describe a unique case of bilateral gonadal tumors occurring in an infant with mixed gonadal dysgenesis (MGD). MGD is an intersex disorder characterized by asymmetric dysgenetic gonads, ambiguous genitalia, persistent mullerian structures, and a Y cell line. Patients with MGD are at high risk of developing gonadal tumors, the majority being identified in the second and third decade of life. The most common tumor is a gonadoblastoma, a benign lesion composed of dysplastic germ and sex cord cells. However, the germ cell element can give rise to malignant germinomas such as seminomas, as in our case. 1,2 Prophylactic gonadectomy is indicated, but there are no clear recommendations as to when this should occur. The young age of this child emphasizes the importance of very early gonadectomy in patients with MGD that are to be raised in the female gender, and careful monitoring of male infants after early orchiopexy.

Breakpoint analysis of Turner patients with partial Xp deletions: implications for the lymphoedema gene location

BACKGROUNDTurner syndrome is characterised by a 45,X karyotype and a variety of skeletal, lymphoedemic, and gonadal anomalies. Genes involved in the Turner phenotype are thought to be X/Y homologous with...

Radiological Signs of Leri-Weill Dyschondrosteosis in Turner Syndrome

Background/Aims: Leri-Weill dyschondrosteosis (LWD), a mesomelic short stature syndrome with Madelung deformity, was recently reported to be caused by SHOX (short stature homeobox-containing gene) haploinsufficiency. The loss of SHOX on Xp22.32, also called PHOG (pseudoautosomal homeobox-containing osteogenic gene), through structural aberrations of the X chromosome was also implicated in the short stature phenotype and some additional stigmata of Turner syndrome. The aim of this study was to systematically examine left-hand radiographs from Turner girls for the presence of signs of LWD. Methods: We retrospectively studied 168 left-hand radiographs from 54 patients with Turner syndrome (bone age >10.5 years) who were treated with rhGH and seen during the last 10 years in our clinic. For comparison, we analyzed 7 radiographs from 5 patients with LWD and 52 radiographs from 20 patients with GH deficiency. The shape of the distal radial epiphysis (triangularisation index = TI) and the carpal angle were quantitatively measured. In addition, we screened for the presence of a premature cleft fusion or an ulnar deviation of the articular surface of the distal radial epiphysis and for fourth metacarpal shortening. One of 54 Turner girls (2%) was affected with LWD and presented with Madelung deformity. Results: No milder forms of Madelung deformity were detected. However, there was a significant trend to a triangular shape of the distal radial epiphysis in Turner syndrome: the median TI was 2.7 in normal controls (range 1.8–3.7), 3.1 in Turner girls (range 2.0–6.3) (p < 0.001 against controls), and 6.0 in patients with LWD (range 3.5–11.0) (p < 0.001 against controls). Conclusions: The triangularisation index did not correlate with the carpal angle (median 122.5

47,Xxx in an adolescent with premature ovarian failure and autoimmune disease

Background: Premature ovarian failure (POF) is often associated with autoimmune disorders. The 47,XXX karyotype has also been associated with POF and other genitourinary abnormalities. Following is a case of a 17 year old with immune thrombocytopenic purpura (ITP), POF, 47,XXX and a positive antinuclear antibody (ANA).Case Report: A 17 year old Caucasian female was referred to the Adolescent Health Clinic for evaluation of oligomenorrhea with secondary amenorrhea. Thelarche occurred at 12 years, and menarche at 13 years of age. Since then she had a total of five menstrual periods, spaced 1–15 months apart and lasting 3–5 days. Her last menstrual period was six months prior to presentation. Past medical history was significant for chronic ITP diagnosed seven months prior to presentation, when she developed easy bruising. She was treated with IV gamma globulin and had a moderate response, but relapsed several weeks later. She was started on oral prednisone and had a good response, but continued to relapse whenever steroids were tapered. She was therefore maintained on prednisone 10 mg QOD. There was no family history of irregular menses or autoimmune disease. Physical exam revealed a well-appearing, slightly Cushingoid 17 year old. Physical and cognitive development were age-appropriate. There were no stigmata of Turner Syndrome. The thyroid was normal. Breasts were Tanner 5; public hair was Tanner 3. The external genitalia were normal and appeared well-estrogenized. The remainder of the exam was unremarkable. Pelvic ultrasound demonstrated a normal uterus and ovaries. Laboratory evaluation was significant for elevated gonadotropins and nondetectable estradiol. ANA was positive at 1:320 with a speckled pattern. Blood counts, serologies, complement levels, and coagulation studies were otherwise normal. Cytogenetic studies revealed a 47,XXX karyotype. The patient was placed on an estrogen/norethindrone hormone replacement patch for premature ovarian failure. To date, she has developed no further symptoms, and does not meet criteria for a diagnosis of systemic lupus erythematosis.Conclusions: A 47,XXX karyotype was found in a 17 year old with POF and ITP with a positive ANA. The presence of known autoimmune disease in a woman with POF should not dissuade the physician from evaluating for a potential genetic cause.