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Last updated: 3/3/2025
Years published: 1995, 1996, 1997, 1998, 2001, 2011, 2014, 2017, 2020, 2024, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Dr. Carole Samango-Sprouse, Associate Clinical Professor in the Department of Pediatrics at George Washington University and Adjunct Associate Professor in the Department of Human and Molecular Genetics at Florida International University, for assistance in the preparation of this report.
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47, XXX (trisomy X) is a chromosomal disorder that affects females and is caused by a female having an extra X chromosome. Normally, females have two X chromosomes, but females with 47, XXX have three. The characteristics (phenotype) related to this disorder include a lot of different things but language-based learning disabilities, difficulty performing coordinated movements (developmental dyspraxia), tall stature, low muscle tone (hypotonia) and abnormal bending or curving of the pinky fingers toward the ring fingers (clinodactyly) are seen most often.
47, XXX happens randomly due to errors during the division of reproductive cells in one of the parents. It is important to note that this condition is not preventable.
Trisomy X is uncommon, affecting about 1 in 900 to 1,000 live female births.
The signs and symptoms of 47, XXX can vary greatly between individuals. Many females with this condition are mildly affected or show no symptoms at all. In fact, about 75% of females with 47, XXX are never diagnosed during their lifetime.
It’s important to understand that not all individuals with 47, XXX will have all the symptoms described below. People affected with 47, XXX should talk about their specific symptoms and overall prognosis with their doctors.
The most commons signs and symptoms may include:
For most females with 47, XXX, puberty and fertility are normal. However, some may have:
Less common signs and symptoms may include:
There have been isolated reports of heart abnormalities, cloacal exstrophy (where the rectum, bladder and genitals do not separate completely as the fetus develops), duodenal atresia (where the first part of the small intestine (the duodenum) does not develop properly) and a brain malformation called encephalocele (a sac-like protrusion of the brain and its surrounding membranes through an opening in the skull).
47, XXX is a chromosomal difference (abnormality) where there is an extra X chromosome in females. Chromosomes are found in the nucleus of all the cells in the body and these chromosomes carry the genetic information of all individuals. There are 23 pairs of human chromosomes with the 23rd pair deciding the sex of an individual. Typical males have one X and one Y chromosome (46, XY) while typical females have two X chromosomes (46, XX).
Females with trisomy X have an extra X chromosome causing a 47, XXX karyotype. 47, XXX is not inherited. The extra X chromosome comes from infrequent and random errors during the normal division of reproductive cells in one of the parents (nondisjunction during meiosis). Studies suggest that the risk of such errors increases with advanced maternal age. In most children, the additional X chromosome comes from the mother.
In some females with this condition, only some of their cells have three X chromosomes, while other cells have a normal chromosomal make-up (46, XX/47, XXX mosaicism). This happens in about 20% of children when nondisjunction events occur after conception in the developing fetus (postzygotic nondisjunction). These females are thought to have milder symptoms and fewer developmental and learning problems, but further research is needed. Conditions similar to 47, XXX (variants) have also been described where cells have four or five X chromosomes (tetra X syndrome and penta X syndrome) instead of three. These variants are typically associated with more severe symptoms and findings. (For further information, please see the “Related Disorders” section of this report below.)
In typical females who have two X chromosomes, one of the X chromosomes is “partially turned off” and some, but not all, of the genes on that chromosome are inactivated (X-inactivation). In females with 47, XXX, the extra X chromosome escapes normal X-inactivation. Researchers think that the extra third X chromosome allows some genes that are normally “turned off” to be expressed. They also think that because some genes are expressed too much (overexpression), it may lead to the neurodevelopmental symptoms associated with 47, XXX. However, the link between X-inactivation and symptoms in 47, XXX is not fully understood.
47, XXX is a chromosomal disorder that affects only females. Reported estimates of frequency have varied with the most common estimate being one in 1,000 female births. Since many females with the disorder may have few or no symptoms, researchers think the disorder is greatly underdiagnosed and that the reported number of affected females is inappropriately low (about 10%). With increased diagnosis, more in depth studies may be conducted and more girls with 47, XXX can be appropriately treated.
A diagnosis of 47, XXX may be suspected in a female with the characteristic neurodevelopmental, behavioral, or learning disabilities related to the condition. A diagnosis may be confirmed by specialized tests such as chromosomal microarray analysis performed on blood or cheek (buccal) samples. These tests can show if there is an extra X chromosome in the body’s cells.
47, XXX is increasingly being diagnosed before birth (prenatally) based on cell-free DNA testing, formerly called non-invasive prenatal screening test or NIPT. This test shows if the fetus is at risk for selected chromosomal disorders. Diagnoses are later confirmed with amniocentesis, a test where a sample of the fluid that surrounds the developing fetus is removed and analyzed. Another option is chorionic villus sampling (CVS), which involves removing tissue samples from a portion of the placenta.
Treatment
Due to the wide range of signs and symptoms associated with 47, XXX, treatment is highly individualized and dependent on several factors. These factors can include the age of diagnosis, the specific symptoms someone has and the overall severity of the disorder. Genetic counseling is strongly recommended for people who have the condition and their families to provide education, support and guidance about the condition.
Early diagnosis and intervention are important to have the best possible outcomes. The following assessments and services are recommended for infants and children diagnosed with 47, XXX:
Research shows that girls with 47, XXX improve with early intervention and therapy. Recommended therapies may include:
There are unique medical challenges for adolescent and adult females with 47, XXX. Females who have delayed puberty, irregular menstrual cycles, or fertility concerns should be evaluated for ovarian dysfunction.
The transition into adolescence can be particularly difficult for girls with 47, XXX because of social pressures and neurodevelopmental differences. Short-term counseling or therapy may be beneficial during this time.
With proper medical care, early intervention and a supportive environment, most females with 47, XXX can live normal lives.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Carey J, Battaglia A, Viskochil D and Cassidy S. Management of Genetic Syndromes (4th ed.) John Wiley & Sons, 2021.
Samango-Sprouse, C, and Gropman, AL. X & Y chromosomal variations: hormones, brain development, and neurodevelopmental performance. San Rafael, CA: Morgan & Claypool Publishers, 2017.
Samango-Sprouse CA and Gropman AL. X & Y Chromosomal Variations: Hormones, Brain Development, and Neurodevelopmental Performance. Colloquium Series on The Developing Brain. October, 2016.
Samango-Sprouse CA Frontal Lobe Development in Childhood. The Human Frontal Lobe: Functions and Disorders, 2nd Edition, Eds. BL Miller, and JL Cummings, Guilford Press, New York, 2007.
JOURNAL ARTICLES
Freilinger P, Kliegel D, Hänig S, Oehl-Jaschkowitz B, Henn W, Meyer J. Behavioral and psychological features in girls and women with triple-X syndrome. Am J Med Genet Part A. 2018; 176A: 2284–2291. https://doi.org/10.1002/ajmg.a.40477
Wigby K, D’Epagnier C, Howell S, Reicks A, Wilson R, Cordeiro L, Tartaglia N. Expanding the phenotype of triple X syndrome: A comparison of prenatal versus postnatal diagnosis. Am J Med Genet Part A 2016; 170A: 2870–2881.
Otter M, Schrander-Stumpel CT, Curfs LM. Triple X syndrome: a review of the literature. Eur J Hum Genet. 2010;18(3):265-271. doi:10.1038/ejhg.2009.109
Tartaglia, N.R., Howell, S., Sutherland, A. et al. A review of trisomy X (47,XXX). Orphanet J Rare Dis. 2010; 5: 8. https://doi.org/10.1186/1750-1172-5-8.
Devi R, Tilak P & Rajangam S. Multiple Congenital Anomalies – An Aetiological Evaluation. Bombay Hospital Journal. October, 2007; 49(4).
Krusinskiene V, Alvesalo L, Sidlauskas A. The craniofacial complex in 47, XXX females [published correction appears in Eur J Orthod. 2005 Oct;27(5):532. Krusinskie, Viktorija [corrected to Krusinskiene, Viktorija]]. Eur J Orthod. 2005;27(4):396-401. doi:10.1093/ejo/cji016
Liebezeit BU, Rohrer TR, Singer H, Doerr HG. Tall stature as presenting symptom in a girl with triple X syndrome. J Pediatr Endocrinol Metab. 2003;16(2):233-235. doi:10.1515/jpem.2003.16.2.233
Samango-Sprouse, Carole EdD; Rogol, Alan MD, PhD. XXY: The Hidden Disability and a Prototype for an Infantile Presentation of Developmental Dyspraxia (IDD). Infants & Young Children 15(1):p 11-18, July 2002.
Bender BG, Linden MG, Harmon RJ. Neuropsychological and functional cognitive skills of 35 unselected adults with sex chromosome abnormalities. Am J Med Genet. 2001;102(4):309-313. doi:10.1002/ajmg.1490
Rovet J, Netley C, Bailey J, Keenan M, Stewart D. Intelligence and achievement in children with extra X aneuploidy: a longitudinal perspective. Am J Med Genet. 1995;60(5):356-363. doi:10.1002/ajmg.1320600503
Ratcliffe SG, Pan H, McKie M. The growth of XXX females: population-based studies. Ann Hum Biol. 1994;21(1):57-66. doi:10.1080/03014469400003072
Lin HJ, Ndifourchu F & Patell S. Exstrophy of the cloaca in a 47,XXX child: review of genitourinary malformations in triple-X patients. Am J Med Genet. March, 1993; 45(6):761-3. http://www.ncbi.nlm.nih.gov/pubmed/8456857.
Hood OJ. Multiple congenital anomalies associated with a 47,XXX chromosome constitution. Am J Med Genet. May, 1990; 36(1):73-5. http://www.ncbi.nlm.nih.gov/pubmed/2333909.
Pennington B, Puck M, Robinson A. Language and cognitive development in 47,XXX females followed since birth. Behav Genet. 1980;10(1):31-41. doi:10.1007/BF01067317
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Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
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