Children's Hospital Colorado

X&Y Chromosome Variations

What are X&Y chromosome variations?

X&Y chromosome variations refer to conditions in which a child has an abnormal number of sex chromosomes, also known as X&Y chromosomes.

Other words used to describe X&Y chromosome variations are sex chromosome anomaly, sex chromosome abnormality and sex chromosome aneuploidy.

How do X&Y chromosome variations affect boys and girls?

Males usually have one X and one Y chromosome, and females usually have two X chromosomes. Occasionally, because of problems with the formation of a parent’s sperm or egg, a child can be born with extra or too few sex chromosomes.

For reasons we don't completely understand, children with X&Y chromosome variations can also have developmental delays, learning disabilities and social-emotional difficulties. Babies diagnosed prenatally or during infancy with an X&Y chromosome variation should be monitored closely during early developmental years (birth to 5), including standardized developmental assessments to determine if early interventions are needed. Children with an X&Y chromosome variation should have neuropsychological testing during early academic years to monitor for learning disabilities, attentional problems and social/emotional concerns. Boys with extra X chromosomes need to be seen by an endocrinologist during puberty to help monitor their testosterone levels. Girls who are missing an X chromosome (Turner syndrome) also need ongoing monitoring and treatment by endocrinology, cardiology and other specialties. 

X&Y chromosome variations in males include:

  • 47,XXY (Klinefelter syndrome)
  • 47,XYY
  • 48,XXYY
  • 48,XXXY
  • 49,XXXXY

X chromosome variations in females include:

  • 45,X (Turner syndrome)
  • 47,XXX (Trisomy X or Triple X)
  • 48,XXXX (Tetrasomy X)
  • 49,XXXXX (Pentasomy X)

What causes sex chromosome variations? 

Children are born with X&Y chromosome variations. These conditions are caused by a problem in the division of the X and Y chromosomes during the formation of a parent's egg or the sperm, which are then involved in conception. The exact cause is unknown, and these conditions are typically not inherited.

What are the signs and symptoms of X&Y chromosome variations?

The signs and symptoms of X&Y chromosome variations vary between individuals and depend on the number of extra X or Y chromosomes. Typically, the signs and symptoms of X&Y chromosome variations are more apparent in individuals with a greater number of X or Y chromosomes. While some individuals with X&Y chromosome variations go undiagnosed, signs of these conditions often include developmental delays in speech or motor skills.

There is also an increased risk for emotional difficulties, anxiety, attention problems, hyperactivity, executive functioning difficulties, behavior problems and social skills difficulties, although these are not present in all individuals. When symptoms are significant enough to affect overall functioning in these areas, some individuals can be diagnosed with speech-language disorders, ADHD, learning disabilities in reading or math, autism spectrum disorders, emotional disorders or motor skills disorders.

What do people with sex chromosome variations look like?

Physical features also vary between individuals and depend on the specific type of sex chromosome variation. Individuals with extra X and/or Y chromosomes are often tall, while girls with Turner syndrome, who are missing one X chromosome, are short.

In most cases, infants and children with sex chromosome variations look like typical children and you cannot usually identify individuals based on facial differences. Subtle facial features can be present in some children with extra X&Y chromosomes, including wide spaced eyes and epicanthal folds (a fold of skin on the eyelid that covers the inner corner of the eye). Children with extra X&Y chromosomes may also have curved fifth fingers (clinodactyly), hyper-extensible joints, long limbs and flat feet. Males with an extra X chromosome usually have small testicles and show delayed or incomplete pubertal development due to low levels of testosterone.

Girls with Turner syndrome can have short stature, webbing of the neck, a broad chest and shorter fourth fingers. Girls with Turner syndrome are often treated with growth hormone for short stature. They may also have delayed puberty requiring ongoing follow-up with an endocrinologist. Heart defects can also occur in Turner syndrome, and follow-up with a cardiologist is important.

Any of these features may lead your child's doctor at Children's Hospital Colorado to recommend chromosome testing.

What other medical problems can occur?

Other medical problems that can be associated with X&Y chromosome variations include dental problems, seizures, constipation, asthma and allergies, tremors, elbow abnormalities and heart defects.

The conditions with more chromosomes are usually associated with more medical and neurodevelopmental problems.

What tests are used to diagnose X&Y chromosome variations?

X&Y chromosome variations are identified by genetic testing, usually in the form of a chromosome analysis (also known as a karyotype) or a more detailed chromosome test called a microarray. These tests give doctors information about all the chromosomes in a child's body and they are typically done from a blood sample. X&Y chromosome variations can also be identified in the prenatal period while a mother is pregnant, sometimes through a test of her blood or through other procedures such as amniocentesis.

How are X&Y chromosome variations treated? 

The eXtraordinarY Kids Clinic at Children's Hospital Colorado is a unique interdisciplinary clinic that evaluates and treats children with X&Y chromosome variations. Treatment options for X&Y chromosome variations are designed specific to your child's unique needs. Based on your concerns and your child's symptoms, treatment may involve developmental, psychological or educational interventions like therapies, special education, counseling or medications, which may help children with behavioral, emotional or social issues.

Children with X&Y chromosome variations can often benefit from early interventions for speech delays, gross and fine motor delays, learning disabilities, behavioral issues and social deficits. Therefore, we highly recommend that children with X&Y chromosome variations be seen for a developmental, psychological and medical evaluation shortly after receiving a diagnosis. For infants diagnosed before birth, we recommend consultation with a genetic counselor during pregnancy when the diagnosis is received, and neurodevelopmental evaluations after birth.

Males with an extra X chromosome (XXY/Klinefelter Syndrome, XXYY, XXXY, etc) need care from an endocrinologist, a specialist in hormones, who will monitor for the need for testosterone treatment starting in puberty. This is because the extra X chromosomes usually lead to small testicles and a testosterone deficiency that delays or prevents full pubertal development.

Girls with Turner syndrome should be evaluated by both a cardiologist and an endocrinologist as soon as a diagnosis is made to determine if there are differences in the heart and if growth hormone and other hormone therapies are needed. Consultation with a genetic counselor and geneticist is also important.

Why choose Children's Colorado for sex chromosome variations?

The eXtraordinarY Kids Clinic at Children's Colorado was established in 2007 and is a leading interdisciplinary clinic for children with X&Y chromosome variations. Children and their parents have the opportunity to meet with professionals who have significant experience with these conditions including a developmental pediatrician (Dr. Nicole Tartaglia), endocrinologist (Dr. Shanlee Davis), speech therapist, occupational therapist, clinical psychologist, neuropsychologist and a genetic counselor. Additional specialists for Turner syndrome include genetics (Dr. Laura Pickler), cardiology and adolescent gynecology.

After a clinical evaluation, your family will receive a report summarizing the evaluation and providing specific recommendations for your child based on his or her condition and assessment in order to support your child’s development, academic and emotional needs as well as necessary medical management.

The clinic also provides developmental follow-up for children with X&Y chromosome variations who were diagnosed prenatally or in infancy to help enhance development, evaluate for the need for early intervention therapies, and monitor for medical and neurodevelopmental problems that are commonly associated with the specific sex chromosome variation.

  • The eXtraordinarY Kids Clinic at Children's Colorado is a unique inter-disciplinary clinic for children with X&Y chromosome variations. The team also conducts research in sex chromosome variations.
  • Mathew's story: How the diagnosis of an extra X chromosome helped Mathew find himself
  • AXYS is a national support group dedicated to patient education and support for sex chromosome variations.
  • XXYY Project provides patient education about boys with XXYY syndrome.
  • Turner Syndrome Society and Turner Syndrome Global Alliance aim to educate patients with Turner syndrome and their families and promote advocacy and research initiatives to improve the lives of girls and women with Turner syndrome. There are local support chapters throughout the United States.

For more information or to make an appointment at the eXtraordinarY Kids Clinic, please call 720-777-8361 or send us an email.