48,XXXY syndrome

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Disease Profile

48,XXXY syndrome

1-9 / 100 000

3,310-29,790

US Estimated

5,135-46,215

Europe Estimated

Age of onset

Infancy

ICD-10

Q98.1

Inheritance

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.

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.

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

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.

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.

Not applicable

Other names (AKA)

XXXY syndrome

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]

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other aneuploidies, such as Klinefelter syndrome (47,XXY), 48,XXYY syndrome and 49,XXXXY syndrome (see these terms). Visit the Orphanet disease page for more information.

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

Chromosome Disorder Outreach (CDO)
PO Box 724
Boca Raton, FL 33429
Telephone: +1-561-395-4252
E-mail: https://chromodisorder.org/contact/
Website: https://chromodisorder.org/
Unique – Rare Chromosome Disorder Support Group
G1, The Stables
Station Road West
Surrey
RH8 9EE
United Kingdom
Telephone: +44 (0)1883 723356
E-mail: info@rarechromo.org
Website: https://www.rarechromo.org/

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

Tartaglia N, Ayari N, Howell S, D'Epagnier C, Zeitler P. 48,XXYY, 48,XXXY and 49,XXXXY syndromes: not just variants of Klinefelter syndrome Acta Paediatr. 2011 Jun;100(6):851-60.

References

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.
Visootsak J, Hulten M. XXXY syndrome. Unique. 2008; https://www.rarechromo.org/information/Chromosome_X/XXXY%20syndrome%20FTNW.pdf.

Rare Medical News

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Rare Medical News

Infancy

Q98.1

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

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.

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.

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

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.

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Treatment

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

Selected Full-Text Journal Articles

References

Rare Medical News

Rare Medical News

Infancy

Q98.1

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

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.

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.

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

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.

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Treatment

Related diseases

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

Selected Full-Text Journal Articles

References

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.

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