Rare Neurology News

Disease Profile

48,XXXY 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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Infancy

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ICD-10

Q98.1

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)

XXXY syndrome

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Kidney and Urinary Diseases;

Summary

48,XXXY syndrome is a type of chromosome abnormality characterized by the presence of 2 extra X chromosomes in males. It is sometimes referred to as a variant of Klinefelter syndrome, but differs from Klinefelter syndrome in many ways and is more severe.[1] Signs and symptoms of 48,XXXY syndrome can vary but may include learning difficulties; intellectual disability; low muscle tone (hypotonia); hypogonadism; delayed growth; distinctive facial features; and a variety of birth defects that may affect the genital and musculoskeletal systems. Many also have poorly developed social skills and delayed language development.[1][2] This condition is not inherited and likely results from a random error in cell division. Treatment depends on the features in each individual and often involves the coordinated efforts of a multidisciplinary team of specialists.[1]

Symptoms

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
Azoospermia
Absent sperm in semen
0000027
Decreased testicular size
Small testes
Small testis

[ more ]

0008734
Global developmental delay
0001263
Hypogonadism
Decreased activity of gonads
0000135
Infertility
0000789
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Language impairment
0002463
30%-79% of people have these symptoms
Abnormality of dental enamel
Abnormal tooth enamel
Enamel abnormalities
Enamel abnormality

[ more ]

0000682
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Asthma
0002099
Attention deficit hyperactivity disorder
Attention deficit
Attention deficit disorder
Attention deficit-hyperactivity disorder
Attention deficits
Childhood attention deficit/hyperactivity disorder

[ more ]

0007018
Autism
0000717
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Chronic otitis media
Chronic infections of the middle ear
0000389
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Constipation
0002019
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Depressed nasal ridge
Flat nose
Recessed nasal ridge

[ more ]

0000457
Down-sloping shoulders
Rounded shoulders
Rounded, sloping shoulders
Sloping shoulders

[ more ]

0200021
Elbow dislocation
Dislocations of the elbows
Elbow dislocations

[ more ]

0003042
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Gynecomastia
Enlarged male breast
0000771
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypoplasia of penis
Underdeveloped penis
0008736
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Muscular hypotonia
Low or weak muscle tone
0001252
Open bite
Absence of overlap of upper and lower teeth
Open bite between upper and lower teeth

[ more ]

0010807
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Radioulnar synostosis
Fused forearm bones
0002974
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Scrotal hypoplasia
Smaller than typical growth of scrotum
0000046
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Tall stature
Increased body height
0000098
Taurodontia
0000679
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
5%-29% of people have these symptoms
Abnormal aggressive, impulsive or violent behavior
0006919
Abnormal social behavior
Abnormal social behaviour
0012433
Abnormality of cardiovascular system morphology
0030680
Anxiety
Excessive, persistent worry and fear
0000739
Blepharophimosis
Narrow opening between the eyelids
0000581
Brachycephaly
Short and broad skull
0000248
Cleft palate
Cleft roof of mouth
0000175
Coxa valga
0002673
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay

[ more ]

0000750
Facial asymmetry
Asymmetry of face
Crooked face
Unsymmetrical face

[ more ]

0000324
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Hip dislocation
Dislocated hips
Dislocation of hip

[ more ]

0002827
Inguinal hernia
0000023
Irritability
Irritable
0000737
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

0000303
Obesity
Having too much body fat
0001513
Pulmonary embolism
Blood clot in artery of lung
0002204
Renal dysplasia
0000110
Schizophrenia

Treatment

There is no cure for 48,XXXY syndrome. Treatment depends on the symptoms present in each individual and is best managed by a team of specialists, including cardiologists, orthopedists, speech therapists, neurologists, and endocrinologists. Life expectancy is generally normal in the absence of major complications. Regular medical visits are often needed, in particular to monitor problems with hormone production, infections, and behavior.[1]

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

    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

    • 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 48,XXXY 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 48,XXXY syndrome. Click on the link to view a sample search on this topic.

        Selected Full-Text Journal Articles

          References

          1. Corsini C, Sarda P. 48,XXXY syndrome. Orphanet. May 2011; https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=12832.
          2. Visootsak J, Hulten M. XXXY syndrome. Unique. 2008; https://www.rarechromo.org/information/Chromosome_X/XXXY%20syndrome%20FTNW.pdf.

          Rare Neurology News