45,X/46,XX at the first amniocentesis, and 45,X/47,XXX/46,XX at the repeat amniocentesis and at birth in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the 45,X cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.

OBJECTIVE: We present 45,X/46,XX at the first amniocentesis, and 45,X/47,XXX/46,XX at the repeat amniocentesis and at birth in a pregnancy associated with a favorable fetal outcome, perinatal progressive decrease of the 45,X cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes. CASE REPORT: A 43-year-old, gravida 3, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[4]/46,XX[20]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed arr (X) × 3 [0.24], consistent with 24% mosaicism for triple X. Repeat amniocentesis at 20 weeks of gestation revealed the result of 45,X[17]/47,XXX[8]/46,XX[121]. She was referred for genetic counseling, and the third amniocentesis performed at 30 weeks of gestation revealed the result of 45,X[3]/47,XXX[2]/46,XX[16]. The mother had a karyotype of 46,XX. aCGH analysis on the DNA extracted from uncultured amniocytes showed arr Xp22.33q28 × 2.2 (log2 ratio = 0.15), consistent with 20% mosaicism for triple X. Interphase fluorescence in situ hybridization (FISH) analysis on 100 uncultured amniocytes showed that 11 cells (11%) were monosomy X, seven cells (7%) were triple X, and the others were disomy X. At 39 weeks of gestation, a 3,620-g phenotypically normal female baby was delivered without any phenotypic abnormality. The karyotypes of cord blood, umbilical cord and placenta were 47,XXX[7]/45,X[1]/46,XX[32], 47,XXX[13]/46,XX[27] and 47,XXX[2]/46,XX[38], respectively. When follow-up at age one month, the neonate was phenotypically normal, and FISH analysis on 106 buccal mucosal cells showed that eight cells (7.5%) were monosomy X, seven cells (6.6%) were triple X, and the others were disomy X. CONCLUSION: Mosaic 45,X/46,XX at amniocentesis may be in fact mosaic 45,X/47,XXX/46,XX and can be associated with a favorable fetal outcome and perinatal progressive decrease of the 45,X cell line.

Perinatal detection of disomy X cell line by fluorescence in situ hybridization in a pregnancy with 45,X/47,XXX at amniocentesis, cytogenetic discrepancy in various tissues and a favorable outcome.

OBJECTIVE: We present perinatal detection of disomy X cell line by fluorescence in situ hybridization (FISH) in a pregnancy with 45,X/47,XXX at amniocentesis, cytogenetic discrepancy in various tissues and a favorable outcome. CASE REPORT: A 34-year-old, gravida 3, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X[22]/47,XXX[10]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (X) × 1-2, (1-22) × 2, consistent with 32% mosaicism for monosomy X. She was referred for genetic counseling at 19 weeks of gestation. Prenatal ultrasound findings and parental karyotypes were normal. Repeat amniocentesis at 29 weeks of gestation revealed a karyotype of 45,X[36]/47,XXX[4] (Fig. 1) in cultured amniocytes. Simultaneous molecular analysis on uncultured amniocytes revealed the result of arr (1-22) × 2, Y × 0 by aCGH with no genomic imbalance, and 15% (15/100 cells) mosaicism for disomy X, 61% (61/100 cells) mosaicism for monosomy X and 24% (24/100 cells) mosaicism for triple X by interphase fluorescence in situ hybridization (FISH) analysis. The pregnancy was encouraged to continue and at 37 weeks of gestation, a 2834-g phenotypically normal female baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 45,X[33]/47,XXX[7], 45,X[30]/47,XXX[10] and 47,XXX[38]/45,X[2], respectively. When follow-up at age three months, the neonate was normal in development. FISH analysis on 99 buccal mucosal cells showed 49% (48/99 cells) mosaicism for monosomy X, 8% (8/99 cells) mosaicism for triple X and 43% (42/99 cells) mosaicism for disomy X (Fig. 2). Peripheral blood had a karyotype of 45,X[38]/47,XXX[2]. When follow-up at age nine months, the neonate was normal in development. FISH analysis on 102 buccal mucosal cells showed 11% (11/102 cells) mosaicism for monosomy X, 12% (12/102 cells) mosaicism for triple X and 77% (79/102 cells) mosaicism for disomy X. Peripheral blood had a karyotype of 45,X[30]/47,XXX[10]. CONCLUSION: 45,X/47,XXX at amniocentesis may detect disomy X cell line by FISH analysis and can be associated with postnatal progressive decrease of the aneuploid cell lines, increase of the disomy X cell line and a favorable outcome.

Incidence of sex chromosome aneuploidy in a prenatal population: 27-year longitudinal study in Northern Italy.

OBJECTIVES: The availability of cell-free (cf) DNA as a prenatal screening tool affords an opportunity for non-invasive identification of sex chromosome aneuploidy (SCA). The aims of this longitudinal study were to investigate the evolution and frequency of both invasive prenatal diagnostic testing, using amniocentesis and chorionic villus sampling (CVS), and the detection of SCA in cfDNA samples from a large unselected cohort in Northern Italy. METHODS: The results of genetic testing from CVS and amniotic fluid samples received from public and private centers in Italy from 1995 to 2021 were collected. Chromosomal analysis was performed by routine Q-banding karyotype. Regression analyses and descriptive statistics were used to determine population data trends regarding the frequency of prenatal diagnostic testing and the identification of SCA, and these were compared with the changes in indication for prenatal diagnostic tests and available screening options. RESULTS: Over a period of 27 years, there were 13 939 526 recorded births and 231 227 invasive procedures were performed, resulting in the prenatal diagnosis of 933 SCAs. After the commercial introduction of cfDNA use in 2015, the frequency of invasive procedures decreased significantly (P = 0.03), while the frequency of prenatal SCA detection increased significantly (P = 0.007). Between 2016 and 2021, a high-risk cfDNA result was the indication for 31.4% of detected sex chromosome trisomies, second only to advanced maternal age. CONCLUSIONS: Our findings suggest that the inclusion of SCA in prenatal cfDNA screening tests can increase the prenatal diagnosis of affected individuals. As the benefits of early ascertainment are increasingly recognized, it is essential that healthcare providers are equipped with comprehensive and evidence-based information regarding the associated phenotypic differences and the availability of targeted effective interventions to improve neurodevelopmental and health outcomes for affected individuals. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Resting-state functional connectivity in adults with 47,XXX: a 7 Tesla MRI study.

Triple X syndrome is a sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome, resulting in a karyotype of 47,XXX in affected females. It has been associated with a variable cognitive, behavioral, and psychiatric phenotype, but little is known about its effects on brain function. We therefore conducted 7 T resting-state functional magnetic resonance imaging and compared data of 19 adult individuals with 47,XXX and 21 age-matched healthy control women using independent component analysis and dual regression. Additionally, we examined potential relationships between social cognition and social functioning scores, and IQ, and mean functional connectivity values. The 47,XXX group showed significantly increased functional connectivity of the fronto-parietal resting-state network with the right postcentral gyrus. Resting-state functional connectivity (rsFC) variability was not associated with IQ and social cognition and social functioning deficits in the participants with 47,XXX. We thus observed an effect of a supernumerary X chromosome in adult women on fronto-parietal rsFC. These findings provide additional insight into the role of the X chromosome on functional connectivity of the brain. Further research is needed to understand the clinical implications of altered rsFC in 47,XXX.

Altered subcortical and cortical brain morphology in adult women with 47,XXX: a 7-Tesla magnetic resonance imaging study.

BACKGROUND: Triple X syndrome (47,XXX) is a relatively common sex chromosomal aneuploidy characterized by the presence of a supernumerary X chromosome in females and has been associated with a variable cognitive, behavioural and psychiatric phenotype. 47,XXX may serve as a suitable model for studying the effect of genetic architecture on brain morphology. Previous studies have shown alterations in brain structure in 47,XXX particularly in childhood and adolescence. In this study, we examined subcortical and cortical brain morphology in adult women with 47,XXX using ultra-high field 7T MRI. Given previous evidence of impaired social functioning and emotion recognition in adults with 47,XXX, we also investigated the relationship of these functions with brain morphology. METHODS: Twenty-one adult women with 47,XXX and 22 age- and sex-matched healthy controls were included. Structural T1-weighted images were acquired using a 7-Tesla magnetic resonance scanner. Measures of subcortical brain volumes, cortical surface area and thickness, and cortical folding were obtained and compared between the groups using general linear models. Additionally, we examined potential relationships between brain outcome measures and social functioning and social cognition in 47,XXX using correlation analyses. RESULTS: Adults with 47,XXX showed lower volumes of the thalamus, caudate, putamen, hippocampus, nucleus accumbens and pallidum, and larger lateral ventricle volumes. Lower surface area was found in the superior frontal gyrus and superior temporal gyrus in 47,XXX participants compared to healthy controls. Altered cortical thickness and cortical folding were not present in 47,XXX. Cortical thickness was associated with social cognition in 47,XXX. CONCLUSIONS: Results suggest that a supernumerary X chromosome in females affects subcortical and lateral ventricle volumes, and cortical surface area in adulthood. 47,XXX may serve as a suitable model for studying genetic influences on structural brain morphology across developmental stages in order to understand neurobiological mechanisms underlying cognitive and behavioural impairments.

The comorbidity landscape of 47,XXX syndrome: A nationwide epidemiologic study.

PURPOSE: This study aimed to describe the comorbidity pattern in 47,XXX syndrome. METHODS: This was a registry-based study of hospital diagnoses and prescribed medication in a nationwide cohort of females with 47,XXX (n = 103) and 46,XX/47,XXX (n = 57) in which they were compared with 16,000 age-matched general population female controls. RESULTS: The overall occurrence of hospital diagnoses was significantly increased in females with 47,XXX when compared with controls (incidence rate ratio = 2.1, CI = 1.7-2.5), and when divided into 19 organ-specific groups, there was a significantly increased risk in the following 14 groups: infection, blood, endocrine and metabolism, mental, nervous system, eye, ear, respiratory, oral cavity and gastrointestinal, musculoskeletal, perinatal, congenital malformations, external factors, and "other." The risk of being prescribed any medication was not significantly increased in females with 47,XXX when compared with controls (hazard ratio = 1.2, CI = 0.9-1.4). However, when stratified according to medication groups, a significantly increased risk was detected in 4 of 13 groups. The overall occurrence of hospital diagnoses was also significantly increased when females with 46,XX/47,XXX were compared with controls (incidence risk ratio = 1.3, CI = 1.01-1.8), but generally, in comparison with controls, females with 46,XX/47,XXX were less severely affected than females with 47,XXX. CONCLUSION: The 47,XXX syndrome is associated with an increased occurrence of a wide variety of diseases. Increased awareness of this may contribute to improve counseling and clinical assessment of these patients.

Detection of Cryptic Fragile X Full Mutation Alleles by Southern Blot in a Female and Her Foetal DNA via Chorionic Villus Sampling, Complicated by Mosaicism for 45,X0/46,XX/47,XXX.

We describe a female with a 72 CGG FMR1 premutation (PM) (CGG 55-199) and family history of fragile X syndrome (FXS), referred for prenatal testing. The proband had a high risk of having an affected pregnancy with a full mutation allele (FM) (CGG > 200), that causes FXS through hypermethylation of the FMR1 promoter. The CGG sizing analysis in this study used AmplideX triplet repeat primed polymerase chain reaction (TP-PCR) and long-range methylation sensitive PCR (mPCR). These methods detected a 73 CGG PM allele in the proband's blood, and a 164 CGG PM allele in her male cultured chorionic villus sample (CVS). In contrast, the Southern blot analysis showed mosaicism for: (i) a PM (71 CGG) and an FM (285-768 CGG) in the proband's blood, and (ii) a PM (165 CGG) and an FM (408-625 CGG) in the male CVS. The FMR1 methylation analysis, using an EpiTYPER system in the proband, showed levels in the range observed for mosaic Turner syndrome. This was confirmed by molecular and cytogenetic karyotyping, identifying 45,X0/46,XX/47,XXX lines. In conclusion, this case highlights the importance of Southern blot in pre- and postnatal testing for presence of an FM, which was not detected using AmplideX TP-PCR or mPCR in the proband and her CVS.

Detection of maternal X chromosome abnormalities using single nucleotide polymorphism-based noninvasive prenatal testing.

BACKGROUND: Maternal X chromosome abnormalities may cause discordant results between noninvasive prenatal screening tests and diagnostic evaluation of the fetus/newborn, leading to unnecessary invasive testing. Women with X chromosome abnormalities are at increased risk for reproductive, pregnancy, or other health complications, which may be reduced or ameliorated by early diagnosis, monitoring, and intervention. OBJECTIVE: This study aimed to validate a single nucleotide polymorphism-based noninvasive prenatal test to identify X chromosome abnormalities of maternal origin. STUDY DESIGN: All tests unable to evaluate fetal risk for aneuploidy because of uninformative algorithm results were eligible for inclusion. Two groups of cases were prospectively identified: Group A (n=106) where a maternal X chromosome abnormality was suspected and Group B (control group, n=107) where a fetal chromosome abnormality involving chromosome 13, 18, 21, or X was suspected but did not meet criteria for reporting. Maternal DNA was isolated from the plasma-depleted cellular pellet and sent to a reference laboratory for blinded analysis using chromosomal microarray. A chromosome abnormality involving chromosomes 13, 18, 21, or X was reported by the reference laboratory if ≥5 Mb in size and present in ≥20% of the DNA. RESULTS: A maternal X chromosome abnormality was suspected in 1/1305 tests (149/194,385; 0.08%). In Group A, a maternal X chromosome abnormality was confirmed in 100/106 cases (94.3% positive predictive value, 1-sided 97.5% confidence interval, 88.1%-100.0%). Turner syndrome was the most commonly suspected maternal abnormality (58/106, 54.7%), with confirmation of mosaic or nonmosaic 45,X by microarray in 38/58 (65.5%) cases. Noninvasive prenatal screening tests suspected the presence of maternal 47,XXX with or without mosaicism in 40/106 (37.7%) cases, confirmed by microarray in 38/40 (95.0%). In Group B (n=107), no maternal microarray abnormalities were reported, providing a negative predictive value of 100% (1-sided 97.5% confidence interval, 96.6%-100.0%). CONCLUSION: When noninvasive prenatal testing suspected a maternal X chromosome abnormality, maternal microarray confirmed an X chromosome abnormality with 94.3% positive predictive value. Of the maternal X chromosome abnormalities detected by array, >50% were 45,X. When fetal chromosome abnormalities involving chromosomes 13, 18, 21, or X were suspected, no maternal chromosome abnormalities were reported, yielding a negative predictive value of 100%. Women with maternal X abnormalities suspected with noninvasive prenatal testing may be at increased risk for reproductive and health complications; early evaluation and treatment may prevent long-term consequences or disability.

The epidemiology of sex chromosome abnormalities.

Sex chromosome abnormalities (SCAs) are characterized by gain or loss of entire sex chromosomes or parts of sex chromosomes with the best-known syndromes being Turner syndrome, Klinefelter syndrome, 47,XXX syndrome, and 47,XYY syndrome. Since these syndromes were first described more than 60 years ago, several papers have reported on diseases and health related problems, neurocognitive deficits, and social challenges among affected persons. However, the generally increased comorbidity burden with specific comorbidity patterns within and across syndromes as well as early death of affected persons was not recognized until the last couple of decades, where population-based epidemiological studies were undertaken. Moreover, these epidemiological studies provided knowledge of an association between SCAs and a negatively reduced socioeconomic status in terms of education, income, retirement, cohabitation with a partner and parenthood. This review is on the aspects of epidemiology in Turner, Klinefelter, 47,XXX and 47,XYY syndrome.

Ovarian reserve evaluation in a woman with 45,X/47,XXX mosaicism: A case report and a review of literature.

BACKGROUND: Turner syndrome (TS) is a common chromosomal disorder affecting approximately 1:2,500 live female births. Mosaic 47,XXX karyotype is found in 3%-4% of TS patients. TS phenotype in rare 45,X/47,XXX mosaicism patients is milder than in classic TS, however their ovarian function, especially in the mature age, has not been described in detail. METHODS: A case report and literature review. RESULTS: A 30-year-old woman with menstrual irregularity and primary infertility presented with short stature and multiple nevi on the face without other common TS clinical features. She had spontaneous puberty and menarche but diminished ovarian reserve at the age of 30. Fluorescence in situ hybridization (FISH) indicated 45,X/47,XXX mosaicism, which was once misdiagnosed as 45,X monosomy. Literature review revealed the prevalence of short stature in only 64.3% of 45,X/47,XXX mosaicism cases, that is, much less frequently than in pure 45,X monosomy. The risk of premature ovarian insufficiency in 45,X/47,XXX mosaicism patients is higher, and ovarian failure is usually observed at around 30 years of age. CONCLUSION: FISH should be recommended to evaluate low proportion mosaicism in similar cases. Due to the risk of ovarian failure, fertility preservation for patients with 45,X/47,XXX mosaicism at a younger age must be considered.

Positive predictive value estimates for cell-free noninvasive prenatal screening from data of a large referral genetic diagnostic laboratory.

BACKGROUND: Since its debut in 2011, cell-free fetal DNA screening has undergone rapid expansion with respect to both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this screening tool, both for the originally included common autosomal and sex-chromosomal aneuploidies as well as the more recently added chromosomal microdeletion syndromes, have lagged behind. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations of this screening tool to inform pre- and posttest counseling, pre/perinatal decision making, and medical risk assessment/management. OBJECTIVE: The objective of this study was to determine the positive predictive value and false-positive rates for different chromosomal abnormalities identified by cell-free fetal DNA screening using a large data set of diagnostic testing results on invasive samples submitted to the laboratory for confirmatory studies. STUDY DESIGN: We tested 712 patient samples sent to our laboratory to confirm a cell-free fetal DNA screening result, indicating high risk for a chromosome abnormality. We compiled data from all cases in which the indication for confirmatory testing was a positive cell-free fetal DNA screen, including the common trisomies, sex chromosomal aneuploidies, microdeletion syndromes, and other large genome-wide copy number abnormalities. Testing modalities included fluorescence in situ hybridization, G-banded karyotype, and/or chromosomal microarray analysis performed on chorionic villus samples, amniotic fluid, or postnatally obtained blood samples. Positive predictive values and false-positive rates were calculated from tabulated data. RESULTS: The positive predictive values for trisomy 13, 18, and 21 were consistent with previous reports at 45%, 76%, and 84%, respectively. For the microdeletion syndrome regions, positive predictive values ranged from 0% for detection of Cri-du-Chat syndrome and Prader-Willi/Angelman syndrome to 14% for 1p36 deletion syndrome and 21% for 22q11.2 deletion syndrome. Detection of sex chromosomal aneuploidies had positive predictive values of 26% for monosomy X, 50% for 47,XXX, and 86% for 47,XXY. CONCLUSION: The positive predictive values for detection of common autosomal and sex chromosomal aneuploidies by cell-free fetal DNA screening were comparable with other studies. Identification of microdeletions was associated with lower positive predictive values and higher false-positive rates, likely because of the low prevalence of the individual targeted microdeletion syndromes in the general population. Although the obtained positive predictive values compare favorably with those seen in traditional screening approaches for common aneuploidies, they highlight the importance of educating clinicians and patients on the limitations of cell-free fetal DNA screening tests. Improvement of the cell-free fetal DNA screening technology and continued monitoring of its performance after introduction into clinical practice will be important to fully establish its clinical utility. Nonetheless, our data provide valuable information that may aid result interpretation, patient counseling, and clinical decision making/management.

Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis.

Triple X syndrome (47, XXX) occurs in approximately 1:1,000 female births and has a variable phenotype of physical and psychological features. Prenatal diagnosis rates of 47, XXX are increasing due to non-invasive prenatal genetic testing. Previous studies suggest that prenatal diagnosed females have better neurodevelopmental outcomes. This cross-sectional study describes diagnosis, physical features, medical problems, and neurodevelopmental features in a large cohort of females with 47, XXX. Evaluation included review of medical and developmental history, physical exam, cognitive, and adaptive testing. Medical and developmental features were compared between the prenatal and postnatal diagnosis groups using rate calculations and Fisher's exact test. Cognitive and adaptive tests scores were compared using t-tests. Seventy-four females age 6 months-24 years (mean 8.3 years) participated. Forty-four (59.5%) females were in the prenatal diagnosis group. Mean age of postnatal diagnosis was 5.9 years; developmental delay was the most common indication for postnatal genetic testing. Common physical features included hypertelorism, epicanthal folds, clinodactyly, and hypotonia. Medical problems included dental disorders (44.4%), seizure disorders (16.2%), genitourinary malformations (12.2%). The prenatal diagnosis group had higher verbal (P < 0.001), general ability index (P = 0.004), and adaptive functioning scores (P < 0.001). Rates of ADHD (52.2% vs. 45.5%, P = 0.77) and learning disabilities (39.1% vs. 36.3%, P = 1.00) were similar between the two groups. These findings expand on the phenotypic features in females with Triple X syndrome and support that prenatally ascertained females have better cognitive and functional outcomes. However, prenatally diagnosed females are still at risk for neurodevelopmental disorders. Genetic counseling and treatment recommendations are summarized. © 2016 Wiley Periodicals, Inc.

The Turner syndrome in patient with 45X/47XXX mosaic karyotype--case report.

BACKGROUND: Turner syndrome (TS) is a gonadal dysgenesis related to partial or total lack of one of the X chromosomes. It this report we describe a young patient presenting some somatic features of TS, who underwent spontaneous puberty and was eumenoorheic up to the age of 23. METHODS: Using fluorescent in situ hybridization (FISH) mosaic karyotype (45X[131]/47XXX[9]) of TS and triple X syndrome was found. RESULTS: She presented uncommon for TS somatic hemihypotrophy and underwent growth hormone and surgical therapy. The patient was diagnosed with premature ovarian failure when she was 23, with absent follicular reserve. Clinical features of this case and a few published cases will be reviewed briefly.

Concurrent insulinoma with mosaic Turner syndrome: A case report.

Turner syndrome is a chromosomal abnormality in which the majority of patients have a 45XO karyotype, while a small number have a 45XO/47XXX karyotype. Congenital adrenal hyperplasia has been previously reported in patients with Turner syndrome. Although insulinomas are the most common type of functioning pancreatic neuroendocrine tumor and have been reported in patients with multiple endocrine neoplasias, the tumors have not been reported in patients with mosaic Turner syndrome. The present study reports the first case of an insulinoma in a patient with 45XO/47XXX mosaic Turner syndrome. The patient suffered from recurrent hypoglycemia, which was relieved following ingestion of glucose or food. A 5-h glucose tolerance test was performed and the levels of glucose, C-Peptide and insulin were detected. In addition, computed tomography (CT) and ultrasound scanning were performed to evaluate the possibility of an insulinoma. Pathological examination and karyotyping were performed on a surgical specimen and a whole blood sample, respectively. The patient was found to suffer from premature ovarian failure, and a physical examination was consistent with a diagnosis of Turner syndrome. An ultrasound scan demonstrated streak ovaries and the patient was found to have a 45XO/47XXX karyotype. Furthermore, a lesion was detected in the pancreas following CT scanning, which was identified as an insulinoma following surgical removal and histological examination. In conclusion, the present study reports the first case of an insulinoma in a patient with mosaic Turner syndrome. Since mosaic Turner syndrome and insulinoma are rare diseases, an association may exist that has not been previously identified.

Patients with 47, XXX karyotype who experienced premature ovarian failure (POF): two case reports.

PURPOSE: Pubertal onset and sexual development are usually normal in 47, XXX individuals; however, we report two cases of premature ovarian failure (POF) in infertile women with trisomy X. METHODS: Chromosome analysis was conducted with G-banding and fluorescence in situ hybridization using X- and Y-bearing probe. Hormonal administration was primarily Kaufmann's treatment or long-term estradiol treatment, followed by withdrawal bleeding from estrogen and progesterone. RESULTS: Two patients with trisomy X, aged 31 (patient 1) and 27 years (patient 2), were diagnosed with POF due to hypergonadotropic hypogonadism. Their ovaries were small. Patient 1 had a FSH level of 44.6 mIU/ml and patient 2 had a FSH level of 74.6 mIU/ml. In patient 1, with Kaufmann's treatment, the FSH decreased to 13.5 mIU/ml; however, follicle growth did not occur following HMG stimulation. In patient 2, FSH did not decrease despite Kaufmann's treatment; therefore, she was given a GnRH agonist and her FSH level decreased to 7.1 mIU/ml. However, her ovaries never responded to HMG stimulation. CONCLUSION: We report on two patients with a 47, XXX karyotype who became infertile due to POF. We recommend that when a patient is diagnosed with trisomy X, the possibility of POF must be strongly considered.

Triple x syndrome with short stature: case report and literature review.

BACKGROUND: Triple X syndrome is a sex chromosomal aneuploidy condition characterized by tall stature, microcephaly, hypertelorism, congenital abnormalities, and motor and language delays. It is mainly derived from maternal nondisjunctional errors during meiosis. To highlight the clinical features and diagnosis of triple X syndrome, we present a rare phenotype of the syndrome. CASE PRESENTATION: A 5.9 year-old girl was admitted to our hospital because of short stature. Both her height and weight were below the 3(rd) percentile compared to the normal peers. She was found with mild motor and speech delay. Laboratory investigation showed low level of IGF-1 and zinc, elevated estradiol level and normal result of arginine provocation test. CONCLUSION: Our data suggest that triple X syndrome should also be suspected in patients with short stature, elevated estradiol and low level of IGF-1, even with normal result of arginine provocation test.

Variabilidad fenotípica en pacientes 47, XXX: presentación de cuatro casos nuevos / Phenotypic variability in 47, XXX patients: clinical report of four new cases

El síndrome 47, XXX se debe a un cromosoma extra del par sexual; su incidencia es de 1 en 1000 recién nacidas vivas. Sin embargo, este síndrome no suele sospecharse al nacimiento ni en la infancia. Muchas de estas pacientes son diagnosticadas durante la edad adulta por falla ovárica precoz o esterilidad, debido a la falta de características clínicas específicas .Este trabajo describe cuatro casos de pacientes 47, XXX y su variabilidad fenotípica.

The 47, XXX karyotype has a frequency of 1 in 1000 female newborns. However, this karyotype is not usually suspected at birth or childhood. These patients are usually diagnosed duringadulthood when they develop premature ovarian failure or infertility, because the early phenotype doesn't have anyspecific features. The study describes four cases and the clinical variability of the 47, XXX karyotype.

Variabilidad fenotípica en pacientes 47, XXX: presentación de cuatro casos nuevos / Phenotypic variability in 47, XXX patients: clinical report of four new cases

El síndrome 47, XXX se debe a un cromosoma extra del par sexual; su incidencia es de 1 en 1000 recién nacidas vivas. Sin embargo, este síndrome no suele sospecharse al nacimiento ni en la infancia. Muchas de estas pacientes son diagnosticadas durante la edad adulta por falla ovárica precoz o esterilidad, debido a la falta de características clínicas específicas .Este trabajo describe cuatro casos de pacientes 47, XXX y su variabilidad fenotípica.(AU)

The 47, XXX karyotype has a frequency of 1 in 1000 female newborns. However, this karyotype is not usually suspected at birth or childhood. These patients are usually diagnosed duringadulthood when they develop premature ovarian failure or infertility, because the early phenotype doesnt have anyspecific features. The study describes four cases and the clinical variability of the 47, XXX karyotype.(AU)