Xp11.22 Duplication Syndrome
Xp11.22 duplication syndrome is also called Xp11.22 microduplication syndrome. For this webpage, we will be using the name Xp11.22 duplication syndrome to encompass the wide range of variants observed in the people identified.
What is Xp11.22 duplication syndrome?
Xp11.22 duplication syndrome happens when a person has an extra piece of the X chromosome, one of the body’s 46 chromosomes. Chromosomes are structures in our cells that house our genes. The extra piece can affect learning and how the body develops.
There are several genes within the Xp11.22 region that are involved in intellectual disability. This condition usually affects males and rarely affects female carriers.
Key Role
Genes within the Xp11.22 region are important for brain development and function.
Symptoms
Because genes in the Xp11.22 region are important in brain development and function, many people who have Xp11.22 duplication syndrome have:
- Developmental delay
- Intellectual disability
- Motor delay
- Delayed speech and language development
- Husky or nasal voice
- Obesity
- Early puberty
- Seizures
- Autism
- Attention-deficit/hyperactivity disorder (ADHD)
- Constipation
What causes Xp11.22 duplication syndrome?
Xp11.22 duplication syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Genes are arranged in structures in our cells called chromosomes. Chromosomes and genes usually come in pairs, with one copy from the mother, from the egg, and one copy from the father, from the sperm.
We each have 23 pairs of chromosomes. One pair, called the X and Y chromosomes, differs between biological males and biological females. Biological females have two copies of the X chromosome and all its genes, one inherited from their mother and one inherited from their father. Biological males have one copy of the X chromosome and all its genes,inherited from their mother, and one copy of the Y chromosome and its genes, inherited from their father.
In most cases, parents pass on exact copies of the gene to their child. But the process of making the sperm and egg is not perfect. A variant in the genetic code can lead to physical issues, developmental issues, or both.
The Xp11.22 gene is located on the X chromosome, so variants in this gene can affect biological males and biological females in different ways. Biological males who have variants in this gene will likely have Xp11.22 duplication syndrome.
Biological females who have variants in this gene may or may not have symptoms of Xp11.22 duplication syndrome. Biological females who have one working copy of the gene and one non-working copy are considered to be ‘carriers’. Even if a biological female does not have signs or symptoms of the syndrome, they can pass it along to their children.
X-linked recessive conditions
Research shows that Xp11.22 duplication syndrome is often the result of an inherited variant in Xp11.22. This means that Xp11.22 duplication syndrome happens because the genetic variant was passed down from a biological female parent. Biological females that carry the Xp11.22 variant usually do not have symptoms, but sometimes they might.
Sometimes it results from a spontaneous variant in the Xp11.22 gene in the sperm or egg during development. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child can be the first in the family to have the gene variant.
X-Linked Recessive Genetic Syndrome
Why do I or my child have Xp11.22 duplication syndrome?
No parent causes their child’s Xp11.22 duplication syndrome. We know this because no parent has any control over the chromosome changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The genetic change takes place on its own and cannot be predicted or stopped.
What are the chances that other family members or future children will have Xp11.22 duplication syndrome?
Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family.
The risk of having another child who has Xp11.22 duplication syndrome depends on the genes of both biological parents.
- Biological females who have a variant in the Xp11.22 gene and are pregnant with a daughter have a 50 percent chance of passing on the same genetic variant and a 50 percent chance of passing on the working copy of the gene.
- If they are pregnant with a son, the child has a 50 percent chance of inheriting the genetic variant and the syndrome.
For a symptom-free brother or sister of someone who has Xp11.22 duplication syndrome, the sibling’s risk of having a child who has Xq28 duplication syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing Xp11.22 duplication syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit Xq28 duplication syndrome.
- If the biological mother has the same genetic variant causing Xp11.22 duplication syndrome, and the symptom-free daughter has the variant, the symptom-free daughter’s chance of having a son who has Xp11.22 duplication syndrome is 50 percent.
For a person who has Xp11.22 duplication syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have Xp11.22 duplication syndrome?
As of 2025, over 41 people with Xp11.22 duplication syndrome have been described in medical research.
Do people who have Xp11.22 duplication syndrome look different?
People with Xp11.22 duplication syndrome may look different. Appearance can vary and can include some but not all of these features:
- Lower leg or feet defects
- Bushy eyebrows
- Thin upper lip
- Tapering fingers
How is Xp11.22 duplication syndrome treated?
Scientists and doctors have only just begun to study Xp11.22 duplication syndrome. At this point, there are no medicines designed to treat the syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:
- Physical exams and brain studies
- Genetics consults
- Development and behavior studies
- Other issues, as needed
A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:
- Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
- Guide individualized education plans (IEPs).
Specialists advise that therapies for Xp11.22 duplication syndrome should begin as early as possible, ideally before a child begins school.
If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: epilepsy.com/…t-is-epilepsy/seizure-types
This section includes a summary of information from major published articles and the Simons Searchlight quarterly registry report. It highlights how many people have different symptoms. To learn more about the articles, see the Sources and References section of this guide.
Behavior and development concerns linked to Xp11.22 duplication syndrome
Females have two X chromosomes, and males have one X chromosome and one Y chromosome. In females, one of the X chromosomes is inactivated. X inactivation is a random process where a cell chooses one X chromosome to silence gene expression.
Often, female carriers of an X-linked damaging genetic variant have selective X inactivation of that variant. If the affected X chromosome is inactivated, this means that the Xp11.22 duplication would be silenced or turned off. For some females, the unaffected X chromosome is inactivated, resulting in a person having medical features.
The information below includes mostly males with Xp11.22 duplication syndrome.
Speech and learning
Most people with Xp11.22 duplication syndrome had developmental delay or intellectual disability (usually mild to moderate), motor delay, and speech and/or language disorders.
- 37 out of 39 people had developmental delay or intellectual disability (95 percent)
- 34 out of 36 people had speech and/or language impairment (94 percent)
Behavior
People with Xp11.22 duplication syndrome had behavioral issues, such as features of autism, attention-deficit/hyperactivity disorder (ADHD), and attention or concentration issues.
- 6 out of 18 people had autism or autistic traits (33 percent)
- 29 out of 35 people had ADHD or attention or concentration issues (83 percent)
Brain
Some people with Xp11.22 duplication syndrome had neurological medical issues, including seizures and lower than average muscle tone (hypotonia).
- 5 out of 35 people had seizures (14 percent)
- 5 out of 17 people had hypotonia (29 percent)
Growth
People with Xp11.22 duplication syndrome had growth delay or failure to thrive. Some males had an abnormally small penis (micropenis), small testicles, and undescended testicles (cryptorchidism).
- 9 out of 30 people had growth delay or failure to thrive (30 percent)
- 5 males had genital findings such as micropenis, small testicles and/or undescended testicles
Where can I find support and resources?
Simons Searchlight
Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”
- Learn more about Simons Searchlight: www.simonssearchlight.org/frequently-asked-questions
- Simons Searchlight webpage with more information on Xp11.22 duplication: www.simonssearchlight.org/research/what-we-study/xp11-22-duplication
- Simons Searchlight Facebook group: https://www.facebook.com/groups/xp11.22-duplication
Sources and References
- Grams, S. E., Argiropoulos, B., Lines, M., Chakraborty, P., McGowan-Jordan, J., Geraghty, M. T., Tsang, M., Eswara, M., Tezcan, K., … & Chen, E. (2016). Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications. American Journal of Medical Genetics Part A, 170A(4), 967-977. doi:10.1002/ajmg.a.37519
- Moey, C., Hinze, S. J., Brueton, L., Morton, J., McMullan, D. J., Kamien, B., Barnett, C. P., Brunetti-Pierri, N., Nicholl, J., … & Shoubridge, C. (2016). Xp11.2 microduplications including IQSEC2, TSPYL2 and KDM5C genes in patients with neurodevelopmental disorders. European Journal of Human Genetics, 24(3), 373-380. doi:10.1038/ejhg.2015.123
- Qiao, Y., Liu, X., Harvard, C., Hildebrand, M. J., Rajcan-Separovic, E., Holden, J. J., & Lewis, M. E. (2008). Autism-associated familial microdeletion of Xp11.22. Clinical Genetics, 74(2), 134-144. doi:10.1111/j.1399-0004.2008.01028.x
- Santos-Rebouças, C. B., Boy, R., Fernandes, G. N. S., Gonçalves, A. P., Abdala, B. B., Gonzalez, L. G. C., Dos Santos, J. M., & Pimentel, M. M. G. (2023). A novel Xp11.22 duplication involving HUWE1 in a male with syndromic intellectual disability and additional neurological findings. European Journal of Medical Genetics, 66(4), 104716. doi:10.1016/j.ejmg.2023.104716
- Wang, Q., Chen, P., Liu, J., Lou, J., Liu, Y., & Yuan, H. (2020). Xp11.22 duplications in four unrelated Chinese families: Delineating the genotype-phenotype relationship for HSD17B10 and FGD1. BMC Medical Genomics, 13(1), 66. doi:10.1186/s12920-020-0728-8