XYY Syndrome

What Is It, Causes, Diagnosis, and More

Author: Nikol Natalia Armata, MD

Editor: Alyssa Haag, MD

Editor: Lily Guo, MD

Editor: Kelsey LaFayette, DNP

Illustrator: Abbey Richard, MSc

Modified: Jan 06, 2025

What is XYY syndrome?

XYY syndrome, also known as Jacobs syndrome, is a chromosomal disorder characterized by the presence of an extra Y chromosome (47, XYY). Typically, genetic males have one X and one Y chromosome, but individuals with XYY syndrome possess one X and two Y chromosomes. XYY syndrome is identified in about 1 in every 1,000 genetic males. Most individuals with the XYY karyotype do not exhibit any particular clinical manifestations. Nonetheless, features can include above-average height and, in some cases, severe acne during adolescence. While intelligence is generally within the normal range, individuals with XYY syndrome may face learning disabilities and behavioral challenges.

An infographic detailing the background, causes, signs and symptoms, diagnosis, and treatment of XYY syndrome.

What causes XYY syndrome?

XYY syndrome is usually caused by random cell division errors during the production of sperm cells in the father. Once a sperm cell is produced, it should have either one X or one Y chromosome. However, in some cases, errors occur during cell division (e.g., nondisjunction), leading to a sperm cell with an extra copy of the Y chromosome. If this sperm cell fertilizes an egg with an X chromosome, the resulting zygote has 47 chromosomes, including the extra Y chromosome, thereby leading to XYY syndrome. The chance of this error increases slightly with increased paternal age.

Rarely, cell division errors may occur after conception. In such cases, a mosaic pattern of cells may develop, meaning that the affected individual has two genetically different sets of cells. Some cells may have the typical 46 chromosomes, while others have the extra Y chromosome, resulting in a mix of normal and XYY cells within the body. This resulting mosaicism can add complexity to the phenotype (i.e., observable traits) of individuals with XYY syndrome.

What are the signs and symptoms of XYY syndrome?

The most noticeable physical feature of individuals with XYY syndrome is increased height, typically visible after age five or six, resulting in an average height of about 6 feet, 3 inches by adulthood. While many individuals with XYY have a typical physical appearance, some may experience severe cystic acne, macrodontia (i.e., larger teeth), weak muscle tone, and delayed puberty during adolescence. Notably, fertility and sexual development are typically normal. Boys with XYY syndrome generally exhibit average intelligence, but their IQ may be on average 10 to 15 points lower than their siblings. Mild developmental delays in reaching milestones are common, and up to 50% may experience learning disabilities, including speech delays, language problems, and dyslexia. Behavioral challenges may include irritability, hyperactivity, impulsivity, and, in some cases, antisocial behavior, with an increased risk for attention-deficit and hyperactivity disorder (ADHD), as well as a smaller elevated risk for autism spectrum disorder (ASD).

How is XYY syndrome diagnosed?

Diagnosing XYY syndrome requires a comprehensive clinical evaluation, detailed patient history, and specialized tests, particularly chromosomal analysis, to identify the presence of an extra Y chromosome (47, XYY karyotype). This diagnosis can be made before birth through prenatal testing methods like amniocentesis or chorionic villus sampling (CVS). Amniocentesis involves extracting and analyzing the amniotic fluid surrounding the developing fetus, while CVS entails obtaining tissue samples from a part of the placenta. Of note, amniocentesis as well as CVS, carry a small risk of complications such as miscarriage, infection, bleeding, or injury to the fetus. Chromosomal studies on these samples can reveal the extra Y chromosome, the hallmark of XYY syndrome.

Clinical testing and assessments play an important role in early intervention. Speech and language assessments are recommended within the first 24 months, and reading assessments by school age can help assess for dyslexia. Additionally, behavioral evaluation should be considered for children experiencing symptoms like impulsivity, poor attention span, or difficulty with social skills.

How is XYY syndrome treated?

The treatment of XYY syndrome is primarily symptomatic and supportive, focusing on addressing the individual’s specific challenges. Early intervention is key and people with XYY syndrome often respond well to a variety of therapeutic interventions. Speech therapy and occupational therapy can be beneficial, whereas educational therapy, especially for learning disabilities, is important for academic success. Many difficulties related to XYY syndrome can improve over time with appropriate care. Managing acne, a common symptom during adolescence, using a combination of topical agents, such as retinoids, and oral medications, like antibiotics or hormonal therapies, may be considered as it can contribute to the individual's self-esteem. Behavioral problems such as attention-deficit and hyperactivity disorder, along with difficulties in social interactions, can be effectively managed through a combination of therapy and, if necessary, medication (e.g., amphetamine, dextroamphetamine). Overall, a comprehensive and individualized treatment approach helps enhance the overall well-being and quality of life of those with XYY syndrome.

What are the most important facts to know about XYY syndrome?

XYY syndrome, also known as Jacobs syndrome, is a chromosomal disorder resulting from an extra Y chromosome (47, XYY). It often manifests with above-average height, acne during adolescence, mild developmental delays, and learning disabilities. The syndrome is usually caused by errors in sperm cell division, leading to an extra Y chromosome. Diagnosis involves chromosomal analysis, and treatment is primarily supportive, addressing the individual’s specific challenges with interventions such as speech therapy, educational therapy, and behavioral management.

References

Bishop DVM, Brookman-Byrne A, Gratton N, et al. Language phenotypes in children with sex chromosome trisomies. Wellcome Open Res. 2019;3:143. Published 2019 Jan 28. doi:10.12688/wellcomeopenres.14904.2

Jo WH, Jung MK, Kim KE, et al. XYY syndrome: a 13-year-old boy with tall stature. Ann Pediatr Endocrinol Metab. 2015;20(3):170-173. doi:10.6065/apem.2015.20.3.170

Salomon LJ, Sotiriadis A, Wulff CB, Odibo A, Akolekar R. Risk of miscarriage following amniocentesis or chorionic villus sampling: Systematic review of literature and updated meta‐analysis. Ultrasound in Obstetrics & Gynecology. 2019;54(4). doi:https://doi.org/10.1002/uog.20353

Shah AH, Manjunatha BS, Bindayel NA, Khounganian R. Oral health management of a patient with 47,XYY syndrome. BMJ Case Rep. 2013 Dec 5;2013:bcr2013010408. doi: 10.1136/bcr-2013-010408. PMID: 24311410; PMCID: PMC3863099