OBJECTIVE: To explore the genetic characteristics of idic(X)(p11.22) in Turner syndrome (TS). METHODS: Two fetuses suspected for sex chromosome abnormalities or ultrasound abnormalities were selected from Chengdu Women's and Children's Central Hospital in October 2020 and June 2020, and amniotic fluid samples were collected for G-banded chromosomal karyotyping analysis, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH). RESULTS: The two fetuses were respectively found to have a karyotype of 45,X[47]/46,X,psu idic(X)(p11.2)[53] and 46,X,psu idic(X)(p11.2). CMA found that both had deletions in the Xp22.33p11.22 region and duplications in the p11.22q28 region. FISH showed that the centromeres in both fetuses had located on an isochromosome. CONCLUSION The combination of karyotyping analysis, FISH, and CMA is useful for the delineation of complex structural chromosomal aberrations. High-resolution CMA can accurately identify chromosomal breakpoints, which can provide a clue for elucidating the mechanism of chromosomal breakage and rearrangement.
Female ; Pregnancy ; Humans ; Turner Syndrome/genetics* ; In Situ Hybridization, Fluorescence ; Sex Chromosome Aberrations ; Centromere ; Prenatal Diagnosis

PURPOSE: The aim of this study was to investigate the clinicopathological features of premature ovarian insufficiency (POI) associated with chromosomal abnormalities. MATERIALS AND METHODS: This was a retrospective study of POI patients with chromosomal abnormalities diagnosed between January 2009 and December 2017. The definition of POI is based on hypergonadotropinism of 40 or greater in follicle stimulating hormone (FSH) measurements at age 40 years or less. FSH was measured twice at least 4 weeks apart. Karyotyping using peripheral blood for chromosomal testing was conducted in all patients diagnosed with POI. We analyzed the clinical characteristics and genetic causes of patients who were diagnosed with POI. RESULTS: Forty patients were diagnosed with POI including 9 (22.5%) with identified chromosomal abnormalities. The mean age at diagnosis was 23.1±7.8 years (ranging between 14 and 39). Three patients did not experience menarche. The presenting complaints were short stature in one case, one case of amenorrhea with ambiguous external genitals, one case of infertility, and six related to menstruation such as oligomenorrhea or irregular rhythm. Turner syndrome was diagnosed in four cases, Xq deletion in one case, trisomy X in two cases, and 46,XY disorder of sexual development in two other patients. CONCLUSION: Patients diagnosed with POI carrying the same type of chromosomal abnormality manifest different phenotypes. The management protocol also needs to be changed depending on the diagnosis. A karyotype is indicated for accurate diagnosis and proper management of POI in patients, with or without stigmata of chromosomal abnormalities.
Amenorrhea ; Christianity ; Chromosome Aberrations ; Diagnosis ; Female ; Follicle Stimulating Hormone ; Humans ; Infertility ; Karyotype ; Karyotyping ; Menarche ; Menstruation ; Oligomenorrhea ; Phenotype ; Retrospective Studies ; Sexual Development ; Trisomy ; Turner Syndrome

Constitutional delay of growth and puberty (CDGP) is the most common cause of delayed puberty (DP), is mainly found in males, and is characterized by short stature and delayed skeletal maturation. A family history of the subject comprising the timing of puberty in the parents and physical examination may provide clues regarding the cause of DP. Delayed onset of puberty is rarely considered a disease in either sex. In fact, DP usually represents a common normal variant in pubertal timing, with favorable outcomes for final height and future reproductive capacity. In adolescents with CDGP, a linear growth delay occurs until immediately before the start of puberty, then the growth rate rapidly increases. Bone age is often delayed. CDGP is a diagnosis of exclusion; therefore, alternative causes of DP should be considered. Functional hypogonadotropic hypogonadism may be observed in patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions including celiac disease, inflammatory bowel diseases, kidney insufficiency, and anorexia nervosa. Permanent hypogonadotropic hypogonadism (pHH) showing low serum value of testosterone or estradiol and blunted follicle-stimulating hormones (FSH) and luteinizing hormones (LH) levels may be due to abnormalities in the central nervous system. Therefore, magnetic resonance imaging is necessary to exclude morphological abnormalities and neoplasia. Moreover, pHH may be isolated, as observed in Kallmann syndrome, or associated with other hormone deficiencies, as found in panhypopituitarism. Baseline or gonadotropin-releasing hormone pituitary stimulated gonadotropin level is not sufficient to easily differentiate CDGP from pHH. Low serum testosterone in male patients and low estradiol values in female patients, associated with high serum FSH and LH levels, suggest a diagnosis of hypergonadotropic hypogonadism. A genetic analysis can reveal a chromosomal abnormality (e.g., Turner syndrome or Klinefelter syndrome). In cases where the adolescent with CDGP is experiencing psychological difficulties, treatment should be recommended.
Adolescent ; Anorexia Nervosa ; Celiac Disease ; Central Nervous System ; Chromosome Aberrations ; Diagnosis ; Estradiol ; Female ; Gonadotropin-Releasing Hormone ; Gonadotropins ; Humans ; Hypogonadism* ; Inflammatory Bowel Diseases ; Kallmann Syndrome ; Lutein ; Magnetic Resonance Imaging ; Male ; Parents ; Physical Examination ; Puberty ; Puberty, Delayed* ; Renal Insufficiency ; Testosterone ; Turner Syndrome

Partial hydatidiform mole and coexisting fetus is a rare entity with antecedent high risk of maternal and fetal complications, and risk of persistent trophoblastic disease in later life. Here, we report a case of twin pregnancy with live fetus identified as 45,X and normal placenta and another partial mole. Ultrasound scan at 10 weeks showed a hydrops fetus with a focal area of multicystic placenta. The patient underwent chorionic villus sampling and amniocentesis for chromosomal analysis, and the result was 45,X. Based on these finding, the patient then underwent induced abortion. Pathological examination (immunohistochemical staining) of the placenta confirmed the partial mole. This report suggests that careful prenatal ultrasonography and appropriate karyotyping in a molar pregnancy and coexisting fetus enable early diagnosis and may be beneficial for prognosis.
Abortion, Induced ; Amniocentesis ; Chorionic Villi Sampling ; Early Diagnosis ; Edema ; Female ; Fetus* ; Humans ; Hydatidiform Mole* ; Karyotyping ; Molar* ; Placenta ; Pregnancy ; Pregnancy, Twin ; Prognosis ; Trophoblasts ; Turner Syndrome* ; Twins ; Ultrasonography ; Ultrasonography, Prenatal

Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.
Asian Continental Ancestry Group ; Early Diagnosis ; Growth Charts* ; Humans ; Methods ; Noonan Syndrome* ; Selection Bias ; Turner Syndrome*

Newly developed genetic techniques can reveal mosaicism in individuals diagnosed with monosomy X. Noninvasive prenatal diagnosis using maternal blood can detect most fetuses with X chromosome abnormalities. Low-dose and ultralow-dose estrogen replacement therapy can achieve a more physiological endocrine milieu. However, many complicated and controversial issues with such treatment remain. Therefore, lifetime observation, long-term studies of health problems, and optimal therapeutic plans are needed for women with Turner syndrome. In this review, we discuss several diagnostic trials using recently developed genetic techniques and studies of physiological hormone replacement treatment over the last 5 years.
Diagnosis ; Estrogen Replacement Therapy ; Female ; Fetus ; Genetic Techniques ; Hormone Replacement Therapy ; Humans ; Mosaicism ; Prenatal Diagnosis ; Turner Syndrome* ; X Chromosome

There are currently no published cases that report concomitant Turner syndrome (TS), 2q37 deletion syndrome and X-linked hypophosphatemic rickets (XLH). Interestingly, since the clinical phenotypes of TS and 2q37 deletion syndrome overlap, the correct diagnosis may be missed without a standardized approach to genetic testing consisting of both karyotype and microarray. Both chromosome anomalies have been associated with short stature and a variety of skeletal abnormalities however to date no reports have associated these syndromes in association with a phosphate regulating endopeptidase homolog, X-linked (PHEX) gene deletion resulting in XLH. We report a 3-year-old female with 3 concurrent genetic disorders including a 9.98 Mb terminal deletion of chromosome 2: del(2)(q37.1;q37.3), XLH secondary to a small microdeletion of part of the PHEX gene, and mosaic TS (mos 45,X[32]/46,X[18]). This is the first case report of a patient with 2q37 deletion syndrome and mosaic TS (mos 45,X[32]/46,X[18]) found to have XLH secondary to an interstitial constitutional PHEX gene deletion. Her severe phenotype and multiple genotypic findings reinforce the importance of thorough genetic testing in the setting of complicated phenotypic presentations.
Bone Diseases ; Child, Preschool* ; Chromosomes, Human, Pair 2 ; Diagnosis ; Familial Hypophosphatemic Rickets* ; Female* ; Gene Deletion ; Genetic Testing ; Humans ; Karyotype ; Microarray Analysis ; Phenotype ; PHEX Phosphate Regulating Neutral Endopeptidase ; Turner Syndrome*

Swyer Syndrome is a pure form of gonadal dysgenesis that although rare, should not be disregarded in the differential diagnosis of patients who present with primary amenorrhea and abdominopelvic mass. The dysgenetic gonads fail to produce antimullerian hormone in an individual with Swyer Syndrome who is genetically male, resulting in feminization and absence of virilization. Phenotypically female, they usually seek consult at a later time during their teenage years due to primary amenorrhea. Our index patient consulted due to a large abdominopelvic mass and primary amenorrhea. Hormonal assay showed a hypergonadotropic hypogonadism endocrinologic milieu, and on karyotyping, showed a genetically male individual. This paper shall discuss an in-depth pre-operative, surgical and post-operative management of patients diagnosed with Swyer Syndrome.

Human ; Female ; Adolescent ; Anti-mullerian Hormone ; Amenorrhea ; Feminization ; Diagnosis, Differential ; Gonadal Dysgenesis, 46,xy ; Turner Syndrome ; Gonadal Dysgenesis ; Karyotyping ; Virilism ; Hypogonadism ; Gonads

Noninvasive prenatal test (NIPT) is a novel screening method for the diagnosis of fetal chromosomal aneuploidies. NIPT is based on technology that detects cell-free fetal DNA in maternal plasma and analyzes it with massively parallel sequencing technology to determine whether the fetus is at risk of trisomy 21, trisomy 18, trisomy 13 or sex chromosome abnormalities (SCAs). NIPT has been reported to have sensitivity of 99% and a false positive rate of less than 1% for detecting trisomy 21 and trisomy 18. Although extension of the application of NIPT to other SCAs has been attempted, there are concerns in extending NIPT to SCAs because of maternal or fetal mosaicism, undetected maternal SCAs, and multiple pregnancies. Recently, we assessed a pregnancy with the rare Turner syndrome mosaicism 45, X/47, XXX, which was reported as 45, X with NIPT. We present the case here and briefly review the current literatures on NIPT in testing for fetal monosomy X. To the best of our knowledge, this is the first report of the 45, X/47, XXX mosaicism in Korea to be reported as 45, X by NIPT with whole genome sequencing. This case report will provide valuable information for counseling women who want to undergo NIPT.
Aneuploidy ; Counseling ; Diagnosis ; DNA ; Down Syndrome ; Female ; Fetus ; Genome ; High-Throughput Nucleotide Sequencing ; Humans ; Korea ; Mass Screening ; Mosaicism* ; Plasma ; Pregnancy* ; Pregnancy, Multiple ; Prenatal Diagnosis ; Sex Chromosome Aberrations ; Trisomy ; Turner Syndrome*

BACKGROUND AND PURPOSE: Duchenne and Becker muscular dystrophies are the most common X-linked recessive muscular dystrophies. Dystrophin gene mutations usually affect men, but reportedly 2.5-7.8% of women are affected and are classified as symptomatic carriers. The aim of this study was to clinically and genetically characterize symptomatic female dystrophinopathy carriers. METHODS: The clinical and genetic data of 11 female dystrophinopathy carriers among 285 patients who underwent multiplex ligation-dependent probe amplification (MLPA) analysis for the dystrophin gene were reviewed. Women with muscle weakness and/or dilated cardiomyopathy were classified as symptomatic carriers, while subjects with high serum creatine kinase (CK) levels and/or minor myopathic signs such as muscle cramps and myalgia were classified as asymptomatic. RESULTS: Twelve female carriers were identified, but 1 symptomatic carrier who also had Turner syndrome was excluded from the study. Of the 11 included female carriers, 4 were symptomatic and 7 were asymptomatic. The age at symptom onset in the symptomatic female carriers ranged from 15 to 31 years (mean, 30.6 years), and the age at diagnosis for asymptomatic carriers ranged from 4 to 38 years (mean, 24.5 years). Serum CK levels were markedly elevated (mean, 1,301 IU/mL) in three of the four (75%) symptomatic female carriers, and mildly elevated in three of the seven (42%) asymptomatic female carriers. Symptomatic female carriers typically presented with asymmetric bilateral leg weakness as the initial symptom, with aggravated symptoms after labor. CONCLUSIONS: Female dystrophinopathy is not uncommon, and it is an important factor with respect to males with dystrophinopathy who may be born to such patients. Screening with MLPA is useful because it can aid in early diagnosis and appropriate management.
Cardiomyopathy, Dilated ; Creatine Kinase ; Diagnosis ; Dystrophin ; Early Diagnosis ; Female ; Humans ; Leg ; Male ; Mass Screening ; Multiplex Polymerase Chain Reaction ; Muscle Cramp ; Muscle Weakness ; Muscular Dystrophies ; Myalgia ; Turner Syndrome