Rare Endocrinology News

Disease Profile

47 XXX syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-5 / 10 000

33,100 - 165,500

US Estimated

1-5 / 10 000

51,350 - 256,750

Europe Estimated

Age of onset

Infancy

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ICD-10

Q97.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Trisomy X; Triple X syndrome; Triple-X female;

Categories

Chromosome Disorders; Congenital and Genetic Diseases; Endocrine Diseases;

Summary

47 XXX syndrome, also called trisomy X or triple X syndrome, is characterized by the presence of an additional (third) X chromosome in each of a female's cells (which normally have two X chromosomes). An extra copy of the X chromosome is associated with tall stature, learning problems, and other features in some girls and women. Seizures or kidney abnormalities occur in about 10 percent of affected females. 47 XXX syndrome is usually caused by a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes.[1] Treatment typically focuses on specific symptoms, if present.[2] Some females with 47 XXX syndrome have an extra X chromosome in only some of their cells; this is called 46,XX/47,XXX mosaicism.[1]

Symptoms

Many women with 47 XXX syndrome have no symptoms or only mild symptoms. In other cases, symptoms may be more pronounced.[2] Females with 47 XXX syndrome may be taller than average, but the condition usually does not cause unusual physical features. Minor physical findings can be present in some individuals and may include epicanthal folds, hypertelorism (widely spaced eyes), upslanting palpebral fissures, clinodactyly, overlapping digits (fingers or toes), pes planus (flat foot), and pectus excavatum.[3] The condition is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills (such as sitting and walking), weak muscle tone (hypotonia), and behavioral and emotional difficulties are also possible, but these characteristics vary widely among affected girls and women. Seizures or kidney abnormalities occur in about 10 percent of affected females. Most females with the condition have normal sexual development and are able to conceive children.[2][1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of chromosome segregation
0002916
30%-79% of people have these symptoms
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Global developmental delay
0001263
Muscular hypotonia
Low or weak muscle tone
0001252
Specific learning disability
0001328
Tall stature
Increased body height
0000098
5%-29% of people have these symptoms
Anxiety
Excessive, persistent worry and fear
0000739
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Depressivity
Depression
0000716
Hip dysplasia
0001385
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Multicystic kidney dysplasia
0000003
Pectus excavatum
Funnel chest
0000767
Renal hypoplasia/aplasia
Absent/small kidney
Absent/underdeveloped kidney

[ more ]

0008678
Secondary amenorrhea
Previous menstrual periods stop
0000869
Seizure
0001250
Tremor
0001337
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582

Diagnosis

47 XXX syndrome may first be suspected based on the presence of certain developmental, behavioral or learning disabilities in an individual. The diagnosis can be confirmed with chromosomal analysis (karyotyping), which can be performed on a blood sample. This test would reveal the presence of an extra X chromosome in body cells. 47 XXX syndrome may also be identified before birth (prenatally), based on chromosomal analysis performed on a sample taken during an amniocentesis or by a chorionic villus sampling (CVS) procedure.[4] However, in these cases, confirmation testing with a test called FISH, which gives more details of the chromosomes, is recommended in order to evaluate the fetus for mosaicism (when only some of the cells have the extra X chromosome).[5]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is no cure for 47 XXX syndrome, and there is no way to remove the extra X chromosome that is present in an affected individual's cells. Management of the condition varies and depends on several factors including the age at diagnosis, the specific symptoms that are present, and the overall severity of the disorder in the affected individual. Recommendations include:[4][6]

    • Early intervention services for infants and children that are diagnosed with the condition. Evidence suggests that children with 47 XXX syndrome are very responsive to early intervention services and treatment. These services may include speech, occupational, physical or developmental therapy, starting in the early months of life or as soon as needs are identified.
    • Periodic screenings throughout childhood: Specific recommendations include developmental assessment by 4 months of age to evaluate muscle tone and strength; language and speech assessment by 12 months of age; pre-reading assessment during preschool years; and an assessment of additional learning disabilities as well as social and emotional problems. 
    • Educational assistance. Receiving educational help to learn techniques and strategies to be successful in school and daily life.
    • Supportive environment and counseling. Girls with triple X syndrome may be more prone to anxiety, as well as behavior and emotional problems. It is important to have a supportive environment and psychological counseling which may help teaching the family how to demonstrate love and encouragement, and discourage behaviors that might negatively impact learning and social functioning.
    • Assistance and support in daily functioning. If there is developmental delays, this assistance and support may include help with activities of daily living, social opportunities and employment.

    It is also recommended that infants and children with 47 XXX syndrome receive kidney and heart evaluations to detect possible abnormalities. Adolescent and adult women who have late periods, menstrual abnormalities, or fertility issues should be evaluated for primary ovarian failure (POF). Additional treatment for this disorder depends on the specific signs and symptoms present in the affected individual.[4]

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • The Mayo Clinic Web site provides further information on 47 XXX syndrome.
        • Genetics Home Reference (GHR) contains information on 47 XXX syndrome. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
        • Unique is a source of information and support for families and individuals affected by rare chromosome disorders. Click on the link to view information about 47 XXX syndrome.

          In-Depth Information

          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss 47 XXX syndrome. Click on the link to view a sample search on this topic.

            References

            1. Triple X syndrome. Genetics Home Reference. June 2014; https://ghr.nlm.nih.gov/condition/triple-x-syndrome.
            2. Triple X syndrome. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/triple-x-syndrome/basics/definition/con-20033705?p=1.
            3. Nicole R Tartaglia, Susan Howell, Ashley Sutherland, Rebecca Wilson, Lennie Wilson. A review of trisomy X (47,XXX). Orphanet Journal of Rare Diseases. May 2010; 11:5-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883963/?tool=pubmed.
            4. Samango-Sprouse C. Trisomy X. National Organization for Rare Disorders (NORD). 2014; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/1024/viewAbstract.
            5. Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L. A review of trisomy X (47,XXX). Orphanet J Rare Dis. May 2010; 11:5-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883963/?tool=pubmed. Accessed 9/24/2014.
            6. Triple X syndrome. Mayo Clinic. December, 2015; https://www.mayoclinic.org/diseases-conditions/triple-x-syndrome/diagnosis-treatment/drc-20350981.

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