Difference between revisions of "Trisomy X"

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 ICD-11 - LD40.0 Complete trisomy 21
Trisomy 21 is a chromosomal abnormality, characterised by the presence of a third (partial or total) copy of chromosome 21, which clinical manifestations include variable intellectual deficiency, muscular hypotonia and joint laxity, often associated with facial dysmorphism and variable malformations (essentially heart and digestive) and a risk of complications (epilepsy, leukemia, auto-immune and endocrine pathologies, earlier aging and Alzheimer disease.


Fluorescent in situ hybridization shows tree copies of the X chromosome in a single cell nucleus.[1]

Trisomy X is a caused by the presence of an extra X chromosome in females (47,XXX instead of 46,XX). This is also the most common female chromosomal abnormality, occurring in approximately 1 in 1,000 female births.

Other abnormalities of chromosome number include: female tetrasomy X (quadruple X, or 48, XXXX) a rare chromosomal disorder and male Klinefelter syndrome, the presence of an additional X chromosome (47, XXY or XXY).

Alternative names: Triplo X syndrome, Trisomy X, 47,XXX, XXX syndrome

Genetic Links: genetic abnormalities | maternal age | Trisomy 21 | Trisomy 18 | Trisomy 13 | Trisomy X | trisomy mosaicism | Monosomy | Fragile X | Williams | Alagille | Philadelphia chromosome | mitochondria | VACTERL | hydatidiform mole | epigenetics | Prenatal Diagnosis | Neonatal Diagnosis | meiosis | mitosis | International Classification of Diseases | genetics

Genital System - Abnormalities

Some Recent Findings

Human X chromosome
  • Pregnancy outcomes in prenatally diagnosed 47, XXX and 47, XYY syndromes[2] "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. 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). 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."
  • Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis[3] "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."
  • A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome[4] "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."
  • A review of trisomy X (47,XXX)[5] "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."
  • Root length in the permanent teeth of women with an additional X chromosome (47,XXX females)[6] "Increased enamel thickness in the teeth of 47,XXX females is apparently caused by the active enamel gene in all X chromosomes having no increased influence on crown dentin formation. These results in 47,XXX females indicate an increase in root dentin development, at least in the mandible, which together with the data on crown formation reflects a continuous long-lasting effect of the X chromosome on dental development."
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Prenatal Diagnosis

Trisomy X karyotype.jpg

Trisomy X Karyotype[7]

The most common prenatal diagnosis is by either amniocentesis or chorionic villi sampling.

Amniocentesis.jpg Cvs.jpg

Links:Amniocentesis | Chorionic villus sampling

Physical Features

Trisomy X Features
Feature Estimated frequency
Tall stature >75th percentile 80 - 89 %
Epicanthal folds 32 - 46 %
Clinodactyly 42 - 65 %
Hypotonia in infancy 55 - 71 %
Genitourinary malformations 5 - 16 %
Seizure disorder 11 - 15 %
Intention tremor 6 - 20 %
Congenital hip dysplasia 2 - 12 %
Constipation/Abdominal pains 12 - 45 %
Premature ovarian failure unknown
Table data source[5]

Tetrasomy X

Tetrasomy X is due to two non-disjunction events in maternal oocyte meiosis. Tetrasomy X (48, XXXX) is a rare female disorder associated with: facial dysmorphism, premature ovarian insufficiency[8] and intellectual disability.[9] A single case study has shown the presence of a Rathke's cleft cyst (RCC).[10] Tetrasomy X in males (49, XXXXY) is a similarly rare sex chromosome aneuploidy with associated limb abnormalities.[11] Male tetrasomy X karyotype.jpg

Male tetrasomy X karyotype[11]


  1. Venkateshwari A, Srimanjari K, Srilekha A, Begum A, Sujatha M, Sunitha T, Nallari P & Jyothy A. (2012). Mosaic triple X syndrome in a female with primary amenorrhea. Indian J Hum Genet , 18, 246-9. PMID: 23162306 DOI.
  2. Gruchy N, Blondeel E, Le Meur N, Joly-Hélas G, Chambon P, Till M, Herbaux M, Vigouroux-Castera A, Coussement A, Lespinasse J, Amblard F, Jimenez Pocquet M, Lebel-Roy C, Carré-Pigeon F, Flori E, Mugneret F, Jaillard S, Yardin C, Harbuz R, Collonge-Rame MA, Vago P, Valduga M, Leporrier N & Vialard F. (2016). Pregnancy outcomes in prenatally diagnosed 47, XXX and 47, XYY syndromes: a 30-year French, retrospective, multicentre study. Prenat. Diagn. , 36, 523-9. PMID: 27018091 DOI.
  3. Stagi S, di Tommaso M, Scalini P, Lapi E, Losi S, Bencini E, Masoni F, Dosa L, Becciani S & de Martino M. (2016). Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis. Fertil. Steril. , 105, 1547-53. PMID: 26952785 DOI.
  4. Lenroot RK, Blumenthal JD, Wallace GL, Clasen LS, Lee NR & Giedd JN. (2014). A case-control study of brain structure and behavioral characteristics in 47,XXX syndrome. Genes Brain Behav. , 13, 841-9. PMID: 25287572 DOI.
  5. 5.0 5.1 Tartaglia NR, Howell S, Sutherland A, Wilson R & Wilson L. (2010). A review of trisomy X (47,XXX). Orphanet J Rare Dis , 5, 8. PMID: 20459843 DOI.
  6. Lähdesmäki RE & Alvesalo LJ. (2010). Root length in the permanent teeth of women with an additional X chromosome (47,XXX females). Acta Odontol. Scand. , 68, 223-7. PMID: 20568965 DOI.
  7. Kodandapani S, Pai MV, Nambiar J & Moka R. (2011). Premature ovarian aging in primary infertility: Triple X syndrome. J Hum Reprod Sci , 4, 153-4. PMID: 22346085 DOI.
  8. Kara C, Üstyol A, Yılmaz A, Altundağ E & Oğur G. (2014). Premature ovarian failure due to tetrasomy X in an adolescent girl. Eur. J. Pediatr. , 173, 1627-30. PMID: 24221609 DOI.
  9. Samango-Sprouse C, Keen C, Mitchell F, Sadeghin T & Gropman A. (2015). Neurodevelopmental variability in three young girls with a rare chromosomal disorder, 48, XXXX. Am. J. Med. Genet. A , 167A, 2251-9. PMID: 26086740 DOI.
  10. Uppal S, Jee YH, Lightbourne M, Han JC & Stratakis CA. (2017). Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst. Hormones (Athens) , 16, 92-98. PMID: 28500832 DOI.
  11. 11.0 11.1 Korgaonkar S & Vundinti BR. (2015). Tetrasomy X in a Child with Upper Limb Deformity. Indian Pediatr , 52, 439. PMID: 26061938


Tartaglia NR, Howell S, Sutherland A, Wilson R & Wilson L. (2010). A review of trisomy X (47,XXX). Orphanet J Rare Dis , 5, 8. PMID: 20459843 DOI.

Visootsak J & Graham JM. (2006). Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J Rare Dis , 1, 42. PMID: 17062147 DOI.


Brambila-Tapia AJ, Rivera H, García-Castillo H, Domínguez-Quezada MG & Dávalos-Rodríguez IP. (2009). 47,XXX/45,X/46,XX mosaicism in a patient with Turner phenotype and spontaneous puberal development. Fertil. Steril. , 92, 1747.e5-7. PMID: 19732877 DOI.

Lester T, de Alwis M, Clark PA, Jones AM, Katz F, Levinsky RJ & Kinnon C. (1994). Trisomy X in a female member of a family with X linked severe combined immunodeficiency: implications for carrier diagnosis. J. Med. Genet. , 31, 717-20. PMID: 7815443

Tennes K, Puck M, Bryant K, Frankenburg W & Robinson A. (1975). A developmental study of girls with trisomy X. Am. J. Hum. Genet. , 27, 71-80. PMID: 1155452

JOHNSTON AW, FERGUSON-SMITH MA, HANDMAKER SD, JONES HW & JONES GS. (1961). The triple-X syndrome. Clinical, pathological, and chromosomal studies in three mentally retarded cases. Br Med J , 2, 1046-52. PMID: 14452136

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Cite this page: Hill, M.A. (2020, October 26) Embryology Trisomy X. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Trisomy_X

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