What is XYY syndrome

XYY syndrome is also known as 47XYY syndrome or Jacob’s syndrome, is characterized by an extra copy of the Y chromosome in each of a male’s cells. Although many males with XYY syndrome are taller than average, the chromosomal change sometimes causes no unusual physical features. Most males with 47XYY syndrome have normal production of the male sex hormone testosterone and normal sexual development, and they are usually able to father children.

XYY syndrome occurs in about 1 in 1,000 newborn boys. Five to 10 boys with XYY syndrome are born in the United States each day. Many affected males are never diagnosed or not diagnosed until later in life.

XYY syndrome is associated with an increased risk of learning disabilities and delayed development of speech and language skills. Affected boys can have delayed development of motor skills (such as sitting and walking) or weak muscle tone (hypotonia). Other signs and symptoms of this condition include hand tremors or other involuntary movements (motor tics), seizures, and asthma. Males with XYY syndrome have an increased risk of behavioral, social, and emotional difficulties compared with their unaffected peers. These problems include attention deficit hyperactivity disorder (ADHD); depression; anxiety; and autism spectrum disorder, which is a group of developmental conditions that affect communication and social interaction.

Physical features related to XYY syndrome can include increased belly fat, a large head (macrocephaly), unusually large teeth (macrodontia), flat feet (pes planus), fifth fingers that curve inward (clinodactyly), widely spaced eyes (ocular hypertelorism), and abnormal side-to-side curvature of the spine (scoliosis). These characteristics vary widely among affected boys and men.

In the past, there were many misconceptions about XYY syndrome. It was sometimes called the super-male disease because men with XYY syndrome were thought to be overly-aggressive and lacking in empathy. Recent studies have shown that this is not the case. Although individuals with XYY syndrome have an increased risk for learning disabilities and behavioral problems, they are not overly aggressive, nor are they at an increased risk of any serious mental illness. Because these boys are at a higher risk for having learning disabilities, they may benefit from speech therapy, tutoring, and general awareness of the specific issues they struggle with. Although the first years of school may be more challenging for boys with XYY syndrome, they generally go on to lead full, healthy, and normal lives.

Treatment of XYY syndrome is symptomatic and supportive. Speech therapy, occupational therapy, or assistance for learning disabilities in the school setting may be of benefit. In most cases, affected individuals are very responsive to early intervention and treatment, and problems may resolve altogether within a few years. Treatment of acne may help an affected individual’s self-image. Attention deficit and hyperactivity disorder, difficulties with social interactions, or other behavioral problems can be treated with therapy or medication the same as in individuals who do not have XYY.

XXY syndrome key features:

• Normal appearance, typically tall stature
• Intelligence usually in the normal range, but an increased need for educational support especially with reading and writing
• Increased vulnerability to ADHD (attention deficit hyperactivity disorder)
• Increased vulnerability to autistic spectrum disorders
• Perhaps increased risk of asthma and epilepsy

Figure 1. XYY syndrome chromosome

Footnote: Result of chromosome study of a 13-year-old boy showing 47,XYY karyotype (arrow indicates the extra Y chromosome).

[Source ¹ ]

How does XXY affect children and adolescents?

Children with XYY syndrome may be language-delayed and have poor muscle tone, leading to poor fine and gross motor skills. They may be shy and very hesitant about any new experiences, such as pre-school or trying new foods. They can seem immature by comparison with other children their age, and their limited verbal skills may contribute to difficulty in play situations.

Many children with XYY syndrome have poor impulse control and attention deficits, which may be diagnosed as attention deficit disorder or attention deficit hyperactivity disorder (ADD or ADHD). Children with XYY syndrome can be misdiagnosed with Asperger syndrome or pervasive developmental disorder. This is because many exhibit social skill deficits, poor verbal abilities, shyness to the point of avoiding eye contact, and rigidity and inflexibility in their play patterns (i.e. insisting on lining up all car and truck toys, and becoming upset when the toys are disturbed). They may have difficulty in interactions with other children and adults. XYY syndrome is not an autism spectrum disorder, even though there appears to be significant overlap of symptoms.

Children who have XYY syndrome may need special supports in school, including the protections of an IEP or 504 Plan. They may also benefit from a teacher’s aide, protection from bullying and special accommodations such as “self-imposed time outs.” A developmental pediatrician or geneticist will often recognize the subtle physical signs of XYY syndrome in a child initially diagnosed with learning disabilities, ADHD, and/or an autism spectrum disorder, leading to genetic testing and a more complete diagnosis. Small testes, a smaller-than-average penis, hypospadius (urethra located on the shaft of the penis) or chryptorchidism (undescended testicle) are included in these physical signs. Other signs include an arm span measure that is greater than the child’s height, and a significant acceleration in height percentile around the age of 6 or 7 years.

Another body disproportion that may be present is leg length (foot to waist) that exceeds head-to-seat measurement. They may have clinodactyly (slightly curved fifth finger), pectus excavatum (a depression in the chest over the sternum), radio-ulnar synostosis (inability to completely straighten the elbow joint), or taurodontism (relatively thin enamel on the tooth with a large, pulpy root area). For adolescents ages 13 or over, failure to begin puberty or to progress through puberty completely may alert the pediatrician to consider and test for XYY syndrome.

How might behavior issues of a boy with XYY syndrome be addressed?

Unfortunately, there is limited current information on how to address behavior issues in a boy with XYY syndrome. Unique (https://www.rarechromo.org/), a web site that provides information and support to families affected by rare chromosome disorders, has published several pamphlets about XYY syndrome and behavior disorders. Unique suggests that parents aim to be patient, calm and firm when dealing with their son’s behavior issues. Establishing predictable routines, rules, and expectations may be helpful. Sometimes professional support and/or medication may be appropriate ². Other helpful strategies include ignoring bad behavior, rewarding good behavior, stopping behavior that is harmful to the boy or others, distracting the boy from difficult behavior by redirecting his attention to a new topic, and allowing a boy time to absorb and accept new information or change ³.

Unique also suggests that parents observe their son’s behavior and try to find the cause of it by making an “ABC” chart to record three things: what comes before a tantrum (the causes or “Antecedents”), details of the “Behaviors” that are concerning, and what follows a tantrum (the “Consequences” or impact of a tantrum on the son and the family as a whole). Gathering this information may prepare parents to speak with a psychologist to assess behavior issues for each individual boy with XYY syndrome ³.

There are several organizations that provide support to children with behavior issues and their families:

• Parent to Parent USA (http://www.p2pusa.org/) is a national non-profit group that aims to connect parents of children with special needs to other parents to promote the sharing of information and support.
• The National Federation of Families for Children’s Mental Health (https://www.ffcmh.org/) works to increase access to services and support for children with mental, emotional, and behavioral challenges.

It may also help to contact your state representative to learn about local organizations and resources.

Is XYY syndrome inherited?

XYY syndrome is usually not inherited from a parent ⁴. Instead, XYY syndrome is typically caused by a random event that happens during the formation of a sperm cell before conception (when the sperm fertilizes the egg). Even though this random event occurs in the sperm cell of the father of a person with 47, XYY syndrome, the syndrome is not inherited from the father because the father himself typically does not have the syndrome ⁴.

It is uncommon for more than one person in a family to have XYY syndrome. If a couple has a child with XYY syndrome, the chances for the couple or family members to have another child with the syndrome are not increased. Men who have 47, XYY syndrome themselves are also not thought to be at an increased risk to have a child with chromosome differences. Some sperm cells of a man with 47, XYY syndrome will have an extra Y chromosome. However, it is thought that these cells are less likely to be able to survive to fertilize an egg. Therefore, the chances for a man with 47, XYY syndrome to have a child with a sex chromosome abnormality are not thought to be increased ².

People with questions about the chance to have a child with a chromosome abnormality are encouraged to speak with a genetic counselor or other genetics professional.

Resources for locating a genetics professional in your community are available online:

• The National Society of Genetic Counselors (https://www.findageneticcounselor.com/) offers a searchable directory of genetic counselors in the United States and Canada. You can search by location, name, area of practice/specialization, and/or ZIP Code.
• The American Board of Genetic Counseling (https://www.abgc.net/about-genetic-counseling/find-a-certified-counselor/) provides a searchable directory of certified genetic counselors worldwide. You can search by practice area, name, organization, or location.
• The Canadian Association of Genetic Counselors (https://www.cagc-accg.ca/index.php?page=225) has a searchable directory of genetic counselors in Canada. You can search by name, distance from an address, province, or services.
• The American College of Medical Genetics and Genomics (http://www.acmg.net/ACMG/Genetic_Services_Directory_Search.aspx) has a searchable database of medical genetics clinic services in the United States.

XYY syndrome causes

People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics. Females typically have two X chromosomes (46,XX), and males have one X chromosome and one Y chromosome (46,XY) in each cell.

XYY syndrome (47XYY syndrome) is caused by the presence of an extra copy of the Y chromosome in each of a male’s cells ⁵.. As a result of the extra Y chromosome, each cell has a total of 47 chromosomes instead of the usual 46. It is unclear why an extra copy of the Y chromosome is associated with tall stature, learning problems, and other features in some boys and men.

Some males with XYY syndrome (47XYY syndrome) have an extra Y chromosome in only some of their cells. This phenomenon is called 46,XY/47,XYY mosaicism.

XYY syndrome inheritance pattern

Most cases of XYY syndrome are not inherited. The chromosomal change usually occurs as a random event during the formation of sperm cells. An error in cell division called nondisjunction can result in sperm cells with an extra copy of the Y chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra Y chromosome in each of the body’s cells.

46,XY/47,XYY mosaicism is also not inherited. It occurs as a random event during cell division in early embryonic development. As a result, some of an affected person’s cells have one X chromosome and one Y chromosome (46,XY), and other cells have one X chromosome and two Y chromosomes (47,XYY).

XYY syndrome symptoms

The signs and symptoms of XYY syndrome (47XYY syndrome) can range from barely noticeable to more severe. It is thought that some males with XYY syndrome (47XYY syndrome) may never be diagnosed or misdiagnosed because the signs and symptoms may not be noticeable ². The great majority of boys and men with an XYY syndrome are never aware of it, because they do not have symptoms that lead to a diagnosis. Only a small fraction of boys and men with XYY syndrome are ever diagnosed: recent estimates suggest 2.5% in the United Kingdom and 20% in Denmark ². For other males, signs and symptoms such as low muscle tone (hypotonia) and/or speech delay may begin in late infancy or early childhood. Some boys with XYY syndrome (47XYY syndrome) may have difficulty in certain subjects in school such as reading and writing. However, boys with XYY syndrome (47XYY syndrome) do not typically have intellectual disability ⁵. Intelligence is usually in the normal range, although IQ is on average 10-15 points lower than siblings.

Other signs and symptoms of XYY syndrome may include asthma, dental problems, and acne ⁶. Boys with XYY syndrome don’t typically have physical features different from most people, but they may be taller than expected. The increased height, which usually becomes apparent after the age of five or six, and results in an average height of about 6 feet, 3 inches by adulthood. Some individuals with XYY syndrome also develop severe cystic acne during adolescence. Fertility and sexual development are normal. Besides the potential for increased height, most affected individuals typically have a normal physical appearance (phenotype). These boys are not expected to have differences in the appearance of the sex organs (genitalia). Some males with XYY syndrome have behavioral differences such as autism spectrum disorder (usually on the milder end) or attention deficit hyperactivity disorder (ADHD). Boys with 47, XYY syndrome are also at an increased risk to have anxiety or mood disorders ².

Most boys with 47, XYY syndrome go through normal sexual development, and fertility is expected to be normal. However, some boys with the XYY syndrome may develop testicular failure (when the testes can’t produce sperm or testosterone), which can lead to problems with fertility ⁷.

Asthma

Most boys with XXY syndrome do not have asthma, but it is more common than in the general population. Asthma was found in almost 39% (35/89) of boys in one large recent study, compared to a general population level of 9.6% ². The authors point out that the extra Y chromosome may be amplifying the risk of atopy, as there is a greater prevalence of atopy/asthma and a reduced relative airway size in boys compared with girls. The Unique 2014 survey ² showed asthma at a lower frequency in 5/20 boys, of varying severity, but all boys were using inhalers, and one had been repeatedly hospitalised with asthma. Unique also found a high rate of chest infections in the first three years of life or later in childhood, with 14/21 families reporting this.

Seizures

There is a possibility that seizures are more common in boys with XXY syndrome than in the general population ². The most comprehensive study to look at this found that among boys diagnosed prenatally, 1/35 had seizures, giving a rate of 3% compared with 1% of unaffected boys. They are treated with standard antiepilepsy drugs. The Unique 2003 survey also suggested that among this highly selected group, seizures were more common than expected in the general population. Eight out of 32 family reports (25 per cent) mentioned seizures; this was by far the most common medical condition mentioned, and can be explained at least in part by the fact that boys with epilepsy are more likely to have their chromosomes examined. Two boys outgrew them in adolescence and there were no reports of seizures occurring in adults. In the 2014 survey, 2/21 boys had seizures, in one case fever-related. Both boys were diagnosed postnatally.

XYY syndrome diagnosis

XYY syndrome may be suspected when a doctor observes signs and symptoms that can be associated with the syndrome such as low muscle tone (hypotonia), speech delay, or learning problems in school. A doctor may then order testing to see if there is a genetic explanation for the signs and symptoms. Tests that may be ordered include ²:

• Karyotype: a test that is used to view all the chromosomes in a cell
• Chromosomal microarray: a test that looks for extra or missing chromosomes or pieces of chromosomes

In some cases, XYY syndrome may be suspected prenatally based on routine screening tests. A diagnosis can be confirmed with prenatal tests such as an amniocentesis or chorionic villus sampling (CVS) ².

It is thought that some people who have XYY syndrome are never diagnosed because they do not have severe signs or symptoms of the syndrome ².

XXY syndrome prognosis

The long-term outlook for people with XXY syndrome is typically good. Boys with XXY syndrome can do well both in school and in building social relationships. Men with 47, XYY syndrome can also have successful careers and families of their own ². Therapies and other management for the syndrome can be important in allowing affected males to reach their full potentials ⁸.

XYY syndrome life expectancy

Two large follow up studies of men with XXY syndrome have revealed that they are likely to die younger than other men. One study of all men diagnosed with XXY syndrome in a single country, Denmark, showed that life expectancy for men with XXY syndrome was 10 years less than for others, with men with XXY syndrome dying on average at 68 years rather than 78 ². Both studies showed an increase in deaths from respiratory diseases, and the Danish study also showed more deaths from cancer, neurological diseases and accidents. The underlying reasons for this are still not understood, but one possibility is men’s socio-economic conditions ².

XYY syndrome treatment

The signs and symptoms of XYY syndrome can be managed with a variety of therapies. Occupational therapy may be recommended for infants and young boys who have low muscle tone (hypotonia), and speech therapy may be recommended for boys who have speech delay. Boys with XYY syndrome may be in special education at school, or they may have extra help in some classes ⁸.

Other management options for boys with XYY syndrome may include behavioral therapy or medications for boys with attention deficit hyperactivity disorder (ADHD) or behavioral problems. If autism spectrum disorder is present, applied behavioral analysis (ABA) therapy may be recommended ². In some cases, hormonal therapy may be used ⁹.

References

1. 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):170-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4623347
2. XYY syndrome. https://www.rarechromo.org/media/information/Chromosome_Y/XYY%20FTNW.pdf
3. Unique. Behavior Difficulties. 2005; http://www.rarechromo.org/files/Behaviour/Behaviour%20Difficulties%20Web%20Version.pdf
4. 47,XYY syndrome. https://ghr.nlm.nih.gov/condition/47xyy-syndrome
5. XYY Syndrome. https://rarediseases.org/rare-diseases/xyy-syndrome/
6. Schedit L, Sanabe ME, and Diniz MB. Oral, physical, and behavioral aspects of patient with chromosome 47, XYY syndrome. Journal of the Indian Society of Pedodontics and Preventive Dentistry. October-December 2015; 33(4):347-350. https://www.ncbi.nlm.nih.gov/pubmed/26381641
7. Borjian Boroujeni P, Sabbaghian M, Vosough Dizaji A, Zarei Moradi S, Almadani N, Mohammadpour Lashkari F, Zamanian MR, and Mohseni Meybodi A. Clinical aspects of infertile 47,XYY patients: a retrospective study. Human Fertility. July 18, 2017; https://www.ncbi.nlm.nih.gov/pubmed/28715980
8. 47,XXY. https://genetic.org/variations/faq/
9. Samango-Sprouse C, Stapleton EJ, Lawson P, Mitchell F, Sadeghin T, Powell S, and Gropman AL. Positive effects of early androgen therapy on the behavioral phenotype of boys with 47,XXY. Am J Med Genet C Semin Med Genet. June 2015; 169(2):150-157. https://www.ncbi.nlm.nih.gov/pubmed/25939399