Talk:Trisomy X

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Cite this page: Hill, M.A. (2021, May 8) Embryology Trisomy X. Retrieved from

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Pregnancy outcomes in prenatally diagnosed 47, XXX and 47, XYY syndromes: a 30-year French, retrospective, multicentre study

Prenat Diagn. 2016 Jun;36(6):523-9. doi: 10.1002/pd.4817. Epub 2016 May 10.

Gruchy N1, Blondeel E2, Le Meur N3, Joly-Hélas G4, Chambon P4, Till M5, Herbaux M6, Vigouroux-Castera A7, Coussement A8, Lespinasse J9, Amblard F10, Jimenez Pocquet M11, Lebel-Roy C12, Carré-Pigeon F13, Flori E14, Mugneret F15, Jaillard S16, Yardin C17, Harbuz R18, Collonge-Rame MA19, Vago P20,21,22, Valduga M23, Leporrier N1, Vialard F2,24. Author information Abstract OBJECTIVE: Sex chromosome aneuploidies are frequently detected fortuitously in a prenatal diagnosis. Most cases of 47, XXX and 47, XYY syndromes are diagnosed in this context, and parents are thus faced with an unexpected situation. The objective of the present study was to characterize a French cohort of prenatally diagnosed cases of 47, XXX and 47, XYY and to evaluate the termination of pregnancy (TOP) rate before and after France's implementation of multidisciplinary centres for prenatal diagnosis in 1997. METHODS: This retrospective study identified respectively 291 and 175 cases of prenatally diagnosed 47, XXX and 47, XYY between 1976 and 2012. For each case, the indication, maternal age, karyotype and outcome were recorded. RESULTS: Most diagnoses of the two conditions were fortuitous. The occurrence of 47, XXX was associated with advanced maternal age. The overall TOP rate was higher for 47, XXX (22.9%) than for 47, XYY (14.6%), although this difference was not statistically significant. However, the TOP rates fell significantly after 1997 (from 41.1% to 11.8% for 47, XXX and from 25.8% to 6.7% for 47, XYY). CONCLUSION: The TOP rates after prenatal diagnoses of 47, XXX and 47, XYY fell significantly after 1997, following France's implementation of multidisciplinary centres for prenatal diagnosis. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd. PMID: 27018091 DOI: 10.1002/pd.4817

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

Am J Med Genet A. 2016 Nov;170(11):2870-2881. doi: 10.1002/ajmg.a.37688. Epub 2016 Sep 19.

Wigby K1,2, D'Epagnier C1, Howell S1,3, Reicks A4, Wilson R3, Cordeiro L1, Tartaglia N5,6.


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.

© 2016 Wiley Periodicals, Inc.

KEYWORDS: 47, XXX; sex chromosome aneuploidy (SCA); triple X syndrome; triplo-X; trisomy X

PMID 27644018 DOI: 10.1002/ajmg.a.37688

Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis

Fertil Steril. 2016 Jun;105(6):1547-53. doi: 10.1016/j.fertnstert.2016.02.019. Epub 2016 Mar 4.

Stagi S1, di Tommaso M2, Scalini P3, Lapi E4, Losi S5, Bencini E5, Masoni F6, Dosa L4, Becciani S3, de Martino M3.


OBJECTIVE: To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome. DESIGN: Cross-sectional study with retrospective analysis. SETTING: University pediatric hospital. PATIENT(S): Fifteen prepubertal subjects (median age 9.0 years, range 6.9-11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9-11.6 years). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test. RESULT(S): All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients. CONCLUSION(S): Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved. KEYWORDS: Triple X syndrome; early puberty; hypergonadotropic hypergonadism; precocious puberty; premature ovarian failure; puberty PMID 26952785

Hypogonadotropic hypogonadism in a trisomy X carrier: phenotype description and genotype correlation

Gynecol Endocrinol. 2016 Jan;32(1):14-7. doi: 10.3109/09513590.2015.1106472. Epub 2015 Nov 16.

Fiorio P1, Rosaia De Santis L2, Cuoco C1, Gimelli G1, Gastaldi R3, Bonatti F2, Ravazzolo R4,5, Bocciardi R4,5.


We report on a 31-year old female who presented at genetic counseling for a small uterus, secondary amenorrhea and sterility. Gonadotropic hormone levels were low, suggesting a Hypogonadotropic Hypogonadism (HH) condition. Cytogenetic analysis demonstrated the presence of Trisomy X associated to an interstitial deletion of chromosome 4q13.2, resulting in the complete loss of a copy of the GNRHR gene. As GNRHR is known to be responsible for an autosomal recessive form of HH, we checked the status of the undeleted allele and we found the Q106R substitution. In conclusion, the results of our cytogenetic and molecular analyses have allowed us to clarify the etiology of the patient's condition. KEYWORDS: 4q13.2; GNRHR; Hypogonadotropic hypogonadism; deletion; genetic counseling; trisomy X

PMID 26572316


A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome

Genes Brain Behav. 2014 Nov;13(8):841-9. doi: 10.1111/gbb.12180. Epub 2014 Oct 27.

Lenroot RK1, Blumenthal JD, Wallace GL, Clasen LS, Lee NR, Giedd JN.


Trisomy X, the presence of an extra X chromosome in females (47,XXX), is a relatively common but under-recognized chromosomal disorder associated with characteristic cognitive and behavioral features of varying severity. The objective of this study was to determine whether there were neuroanatomical differences in girls with Trisomy X that could relate to cognitive and behavioral differences characteristic of the disorder during childhood and adolescence. MRI scans were obtained on 35 girls with Trisomy X (mean age 11.4, SD 5.5) and 70 age- and sex-matched healthy controls. Cognitive and behavioral testing was also performed. Trisomy X girls underwent a semi-structured psychiatric interview. Regional brain volumes and cortical thickness were compared between the two groups. Total brain volume was significantly decreased in subjects with Trisomy X, as were all regional volumes with the exception of parietal gray matter. Differences in cortical thickness had a mixed pattern. The subjects with Trisomy X had thicker cortex in bilateral medial prefrontal cortex and right medial temporal lobe, but decreased cortical thickness in both lateral temporal lobes. The most common psychiatric disorders present in this sample of Trisomy X girls included anxiety disorders (40%), attention-deficit disorder (17%) and depressive disorders (11%). The most strongly affected brain regions are consistent with phenotypic characteristics such as language delay, poor executive function and heightened anxiety previously described in population-based studies of Trisomy X and also found in our sample. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. KEYWORDS: Trisomy X syndrome; X chromosome; XXX; adolescents; brain; children; magnetic resonance imaging; sex chromosome aneuploidy

PMID 25287572


A review of trisomy X (47,XXX)

Orphanet J Rare Dis. 2010 May 11;5:8.

Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L. Source Department of Pediatrics, University of Colorado Denver School of Medicine, 13123 East 16th Ave., Aurora, CO 80045, USA. Abstract Trisomy X is a sex chromosome anomaly with a variable phenotype caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). It is the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births. As some individuals are only mildly affected or asymptomatic, it is estimated that only 10% of individuals with trisomy X are actually diagnosed. The most common physical features include tall stature, epicanthal folds, hypotonia and clinodactyly. Seizures, renal and genitourinary abnormalities, and premature ovarian failure (POF) can also be associated findings. Children with trisomy X have higher rates of motor and speech delays, with an increased risk of cognitive deficits and learning disabilities in the school-age years. Psychological features including attention deficits, mood disorders (anxiety and depression), and other psychological disorders are also more common than in the general population. Trisomy X most commonly occurs as a result of nondisjunction during meiosis, although postzygotic nondisjunction occurs in approximately 20% of cases. The risk of trisomy X increases with advanced maternal age. The phenotype in trisomy X is hypothesized to result from overexpression of genes that escape X-inactivation, but genotype-phenotype relationships remain to be defined. Diagnosis during the prenatal period by amniocentesis or chorionic villi sampling is common. Indications for postnatal diagnoses most commonly include developmental delays or hypotonia, learning disabilities, emotional or behavioral difficulties, or POF. Differential diagnosis prior to definitive karyotype results includes fragile X, tetrasomy X, pentasomy X, and Turner syndrome mosaicism. Genetic counseling is recommended. Patients diagnosed in the prenatal period should be followed closely for developmental delays so that early intervention therapies can be implemented as needed. School-age children and adolescents benefit from a psychological evaluation with an emphasis on identifying and developing an intervention plan for problems in cognitive/academic skills, language, and/or social-emotional development. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated for POF. Patients should be referred to support organizations to receive individual and family support. The prognosis is variable, depending on the severity of the manifestations and on the quality and timing of treatment.

PMID 20459843

X trisomy in a sterile mare

Equine Vet J. 2010 Jul;42(5):469-70.

de Lorenzi L, Molteni L, Zannotti M, Galli C, Parma P.

Department of Animal Science, Milan University, Italy. Abstract This report concerns the cytogenetic analysis, using both C-banding and fluorescence in situ hybridisation techniques, of a sterile mare. Results obtained revealed a 2n = 65, XXX condition with no sign of mosaicism. The work supports the suggestion that X trisomy, rare in horse, causes infertility in mares and is not associated to other clearly visible phenotypic features.

PMID 20636786