BACKGROUND

Turner syndrome (TS) is the most common sex chromosomal abnormality in females resulting from a missing X chromosomal material. This in turn results in a range of clinical manifestations. This study aimed to provide the data on the cases of TS confirmed via chromosomal analysis in a cytogenetics laboratory in the Philippines as well as the role of genetic counseling.

A review of the karyotyping results of the Cytogenetics Laboratory, Institute of Human Genetics, National Institutes of Health, University of the Philippine Manila from 1991 to 2020.

TS accounted for 2.64% of all the samples received from 1991 to 2020. For 30 years, the most common karyotype in TS was the classical TS or the standard monosomy 45, X noted in 195 patients or 37.69% of all patients diagnosed with TS. Mosaicism with a normal female karyotype was noted in 50 patients (9.62%). For the TS variants, the most common is isochromosome Xq seen in 125 patients (24.04%). This is followed by TS with marker chromosome in 55 patients (10.58%) and ring X chromosome in 23 patients (4.42%). Deletion Xp and deletion Xq were noted in 22 patients (4.23%) and 20 patients (3.85%), respectively.

From this study, it can be noted that chromosomal analysis or standard karyotyping is a vital and useful diagnostic tool in TS. The information obtained from it may be useful in clinical decision-making of families and healthcare providers. Its importance in providing adequate genetic counseling cannot be overemphasized.

OBJECTIVE: To explore the prevalence and clinical manifestations of ring chromosomes among children featuring abnormal development. METHODS: From January 2015 to August 2021, 7574 children referred for abnormal development were selected, and their peripheral blood samples were subjected to G-banded chromosomal karyotyping analysis. RESULTS: Twelve cases of ring chromosomes were detected, which have yielded a prevalence of 0.16% and included 1 r(6), 2 r(9), 1 r(13), 1 r(14), 2 r(15), 1 r(21) and 3 r(X). The children had various clinical manifestations including growth and mental retardation, limb malformation, and congenital heart disease. For two children with r(9) and two with r(15) with similar breakpoints, one child with r(9) and one with r(15) only had growth retardation, whilst another with r(9) and another with r(15) also had peculiar facies and complex congenital heart disease. The r(X) has featured some manifestations of Turner syndrome. CONCLUSION Ring chromosomes are among the common causes for severe growth and mental retardation in children with diverse clinical phenotypes. Clinicians should pay attention to those with developmental anomalies and use chromosomal analysis to elucidate their genetic etiology.
Humans ; Ring Chromosomes ; Intellectual Disability/genetics* ; Turner Syndrome/genetics* ; Phenotype ; Heart Defects, Congenital/genetics*

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

Turner syndrome and Mayer-Rokitansky-Kuster-Hauser syndrome are the most common causes of primary amenorrhea. However, mullerian agenesis in patients with Turner syndrome is rare, with only 15 reported cases worldwide. Described in this report is an 18-year-old female who presented with primary amenorrhea, absent secondary sexual characteristics, short stature, webbed neck, and shield chest. Work up revealed hypergonadotropic hypogonadism, absence of normal ovaries and uterus, and hypothyroidism. She had a 45,X karyotype and was diagnosed with a very rare case of Turner syndrome with associated Mayer-Rokitansky-Kuster-Hauser syndrome. Early detection of the etiology of amenorrhea is critical for prompt management and initiation of hormonal replacement. She was counseled on the possible systemic problems associated with her condition. The importance of regular follow-up and continuous care were also emphasized. With the coexistence of these two conditions, adoption is the only option for having children in the Philippines, where oocyte donation and uterine transplantation are currently unavailable.
Turner Syndrome ; Mullerian aplasia

Disorders of sexual development (DSD) defined as congenital conditions associated with atypical development of anatomical, gonadal or chromosomal sex, is a rare condition that may present with ambiguous genitalia. Included in the varied classes of DSD is mixed gonadal dysgenesis which is known to be due to mosaicism, a chromosomal aberration. Mosaic individuals may have concerns on growth, hormone balance, gonadal development, sex of rearing and fertility. This case report presents an 18-year old student who presented with primary amenorrhea, delayed secondary sexual characteristics and phenotypic features of Turner syndrome who, on chromosomal analysis revealed 45X0/46XY mosaicism. The patient underwent operative laparoscopy with bilateral gonadectomy on the basis of the increased risk of development of gonadal malignancy in phenotypic females with Y-chromosome material. Histopathological analysis revealed bilateral streak gonads. Hormone replacement therapy was then initiated for the induction of secondary female sex characteristics, as treatment for estrogen deficiency, for the induction of pubertal growth spurt and for optimization of bone mineral accumulation. Management of disorders of sexual development is challenging, thus the need for a multidisciplinary approach involving experts in endocrinology, gynecology, psychology and genetics.
GONADAL DYSGENESIS, MIXED ; MOSAICISM ; TURNER SYNDROME ; CASTRATION

Pregnancy ; Female ; Humans ; Turner Syndrome/diagnostic imaging* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Ultrasonography, Prenatal ; Risk Factors

Congenital Adrenal Hyperplasia and Turner Syndrome are not very rare diseases. However, their combination may be confounding. Presented here is a case of a 54 year old nulligravid, with primary amenorrhea, short stature, absent breast development, hirsutism, signs of virilization, and clitoromegaly who came in due to hypogastric pain and an enlarging palpable hypogastric mass. Diagnostic procedures and surgical management are discussed.
Congenital Adrenal Hyperplasia ; Turner Syndrome

A 16.5-year-old Indian female presented with secondary amenorrhoea, cubitus valgus, scoliosis and multiple lentigines on the face. Karyotyping revealed mosaic Turner syndrome (TS) with 45, X/46, X iXq. She also had multiple café-au-lait macules and axillary freckles but no neurofibroma and did not fulfil the classic criteria for diagnosis of Neurofibromatosis-1(NF1). Many of her macules were smaller than 15 mm in diameter, which might be due to her hypoestrogenic state. However, exome-sequencing found a pathologic variant consistent with NF1. She was started on daily oral estrogen, and oral progesterone for 10 days every month with close monitoring for neurofibroma and/or glioma expansion. Co-occurrence of NF1 and TS is extremely rare, TS and NF1 can both affect growth and puberty, cause different cutaneous and skeletal deformities, hypertension, vasculopathy and learning disabilities. Our case highlights the need for genetic testing in some cases with NF1 who do not strictly fulfil the NIH diagnostic criteria. We also emphasize the need for close monitoring during therapy with growth hormone, estrogen and progesterone due to the potential risk of tumour expansion in NF1.
Turner syndrome ; Neurofibromatosis 1 ; NF-1

Objective: To investigate the clinical phenotype and genetic characteristics of disorders of sex development (DSD) caused by Y chromosome copy number variant (CNV). Methods: A retrospective analysis was performed on 3 patients diagnosed with DSD caused by Y chromosome CNV admitted to the First Affiliated Hospital of Zhengzhou University from January, 2018 to September, 2022. Clinical data were collected. Clinical study and genetic test were performed by karyotyping, whole exome sequencing (WES), low coverage whole genome copy number variant sequencing (CNV-seq), fluorescence in situ hybridization (FISH) and gonadal biopsy. Results: The 3 children, aged 12, 9, 9 years, the social gender were all female, presented with short stature, gonadal dysplasia and normal female external genital. No other phenotypic abnormality was found except for case 1 with scoliosis. The karyotype of all cases were identified as 46, XY. No pathogenic vraiants were found by WES. CNV-seq determined that case 1 was 47, XYY,+Y(2.12) and case 2 was 46, XY,+Y(1.6). FISH concluded that the long arm of Y chromosome was broken and recombined near Yq11.2, and then produced a pseudodicentric chromosome idic(Y). The karyotype was reinterpreted as mos 47, X, idic(Y)(q11.23)×2(10)/46, X, idic(Y)(q11.23)(50) in case 1. The karyotype was redefined as 45, XO(6)/46, X, idic(Y)(q11.22)(23)/46, X, del(Y)(q11.22)(1) in case 2. 46, XY, -Y(mos) was found by CNV-seq in case 3, and the karyotype of 45, XO/46, XY was speculated. Conclusions: The clinical manifestations of children with DSD caused by Y chromosome CNV are short stature and gonadal dysgenesis. If there is an increase of Y chromosome CNV detected by CNV-seq, FISH is recommended to classify the structural variation of Y chromosome.
Humans ; Female ; DNA Copy Number Variations ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Chromosomes, Human, Y ; Turner Syndrome

OBJECTIVE: To retrospectively analyze sex chromosomal abnormalities and clinical manifestations of children with disorders of sex development (DSD). METHODS: A total of 14 857 children with clinical features of DSD including short stature, cryptorchidism, hypospadia, buried penis and developmental delay were recruited from Zhengzhou Children's Hospital from January 2013 to March 2022. Fluorescence in situ hybridization (FISH) and chromosomal karyotyping were carried out for such children. RESULTS: In total 423 children were found to harbor sex chromosome abnormalities, which has yielded a detection rate of 2.85%. There were 327 cases (77.30%) with Turner syndrome and a 45,X karyotype or its mosaicism. Among these, 325 were females with short stature as the main clinical manifestation, 2 were males with short stature, cryptorchidism and hypospadia as the main manifestations. Sixty-two children (14.66%) had a 47,XXY karyotype or its mosaicism, and showed characteristics of Klinefelter syndrome (KS) including cryptorchidism, buried penis and hypospadia. Nineteen cases (4.49%) had sex chromosome mosaicisms (XO/XY), which included 11 females with short stature, 8 males with hypospadia, and 6 cases with cryptorchidism, buried penis, testicular torsion and hypospadia. The remainder 15 cases (3.55%) included 9 children with a XYY karyotype or mosaicisms, with main clinical manifestations including cryptorchidisms and hypospadia, 4 children with a 47,XXX karyotype and clinical manifestations including short stature and labial adhesion, 1 child with a 46,XX/46,XY karyotype and clinical manifestations including micropenis, hypospadia, syndactyly and polydactyly, and 1 case with XXXX syndrome and clinical manifestations including growth retardation. CONCLUSION Among children with DSD due to sex chromosomal abnormalities, sex chromosome characteristics consistent with Turner syndrome was most common, among which mosaicism (XO/XX) was the commonest. In terms of clinical manifestations, the females mainly featured short stature, while males mainly featured external genital abnormalities. Early diagnosis and treatment are particularly important for improving the quality of life in such children.
Humans ; Male ; Female ; Turner Syndrome/genetics* ; In Situ Hybridization, Fluorescence ; Cryptorchidism ; Hypospadias ; Retrospective Studies ; Quality of Life ; Sex Chromosome Aberrations ; Karyotyping ; Mosaicism ; Disorders of Sex Development/genetics*