Disease Profile

49, XXXYY 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 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset





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)

XXXYY syndrome


Congenital and Genetic Diseases


49, XXXYY syndrome is a chromosome abnormality that occurs when a male inherits two extra copies of the X chromosome and one extra copy of the Y chromosome. The condition is extremely rare with only a handful of cases reported in the medical literature. Signs and symptoms associated with these cases include severe intellectual disability, distinctive facial features, normal to tall stature, gynecomastia, hypogonadism, and behavioral abnormalities. 49, XXXYY syndrome is likely caused by a mistake (called nondisjunction) that occurs at conception or during the formation of the sperm and/or egg. Treatment is based on the signs and symptoms present in each person.[1][2]


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:
80%-99% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
Abnormal plantar dermatoglyphics
Abnormal prints on feet
Abnormality of the cerebral white matter
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

Autistic behavior
Bilateral talipes equinovarus
Club foot on both sides
Decreased serum testosterone level
Decreased serum testosterone levels
Low serum testosterone level
Low serum testosterone levels

[ more ]

Decreased testicular size
Small testes
Small testis

[ more ]

Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

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 ]

Eye folds
Prominent eye folds

[ more ]

Eunuchoid habitus
Finger clinodactyly
Enlarged male breast
Wide-set eyes
Widely spaced eyes

[ more ]

Increased circulating gonadotropin level
Elevated gonadotropins
Elevated serum gonadotropins
Gonadotropin excess

[ more ]

Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Low frustration tolerance
Low-set, posteriorly rotated ears
Male hypogonadism
Decreased function of male gonad
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

Little lower jaw
Small jaw
Small lower jaw

[ more ]

Short penis
Small penis

[ more ]

Moderate global developmental delay
Narrow chest
Low chest circumference
Narrow shoulders

[ more ]

Primary gonadal insufficiency
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

Recurrent upper respiratory tract infections
Recurrent colds
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]



Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.


    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

        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 49, XXXYY syndrome. Click on the link to view a sample search on this topic.


          1. Linden MG, Bender BG, Robinson A. Sex chromosome tetrasomy and pentasomy. Pediatrics. 1995 Oct; 96(4 pt 1):672-682. https://www.ncbi.nlm.nih.gov/pubmed/7567329.
          2. Cowie VA, Singh KR, Wheater R. 49, XXXYY chromosome anomaly in a mentally retarded man. Br J Psychiatry. 1986 Feb; 148:210-212. https://www.ncbi.nlm.nih.gov/pubmed/3697588.