If your child’s test results mentioned “22q13 duplication syndrome,” an unfamiliar name like this can be confusing and worrying.
Here is the conclusion first. This is a chromosomal condition caused by an extra copy (duplication) of the 22q13 region on the long arm of chromosome 22, and it is a different condition from the similarly named “22q13 deletion syndrome (Phelan-McDermid syndrome)” in both cause and typical symptoms. Depending on the size of the duplicated region and which genes are included, the range of symptoms is very wide — from mild speech delay alone to more noticeable developmental delay.
This article covers the chromosomal change behind the condition, how it differs from the easily confused “22q13 deletion syndrome,” the range of symptoms, inheritance patterns and the possibility of unaffected carriers, the relationship with prenatal testing and NIPT, the path to a definitive diagnosis, and treatment and family support. Information is based on public and academic sources including the US NIH Genetic Testing Registry (GTR), case reports published in Molecular Syndromology and Psychiatric Genetics, and guidance from the Japan Society of Obstetrics and Gynecology (JSOG). Let’s go through each point carefully rather than relying on fragmented information.
💡 What this article covers
- What kind of chromosomal change causes 22q13 duplication syndrome
- How it differs from the easily confused “22q13 deletion syndrome (Phelan-McDermid syndrome)”
- Why the range of symptoms is so wide, and why some carriers show no symptoms
- Inheritance patterns (de novo vs. inherited) and what they mean for future pregnancies
- Whether prenatal testing or NIPT can detect this condition
- Treatment options after diagnosis and support available to families
1. What Is 22q13 Duplication Syndrome (Duplication of the SHANK3 Region)
This is a chromosomal condition in which an extra copy of the 22q13 region on the long arm of chromosome 22 causes genes involved in neural development to be overactive, which can affect development and behavior in various ways.
Every cell in the human body normally contains 46 chromosomes (23 pairs). The SHANK3 gene, located at the very tip of the long arm of chromosome 22, provides the blueprint for building synapses — the connections between neurons. The US National Institutes of Health (NIH) Genetic Testing Registry (GTR) lists this condition as arising from a duplication involving the 22q13 region.
According to a case report published in the journal Molecular Syndromology, duplications extending from 22q13.3 to the terminal end (qter) of the chromosome have been reported in roughly 24 cases worldwide to date, making this an extremely rare condition. Rare as it is, it is by no means unprecedented.
A note on naming
You may see this condition referred to by several names in the literature, including “22q13 microduplication syndrome,” “SHANK3 duplication syndrome,” and “distal 22q duplication syndrome.” The exact name can vary depending on the size of the duplicated region and which genes are involved. For simplicity, this article uses the general term “22q13 duplication syndrome” throughout.
2. How It Differs From “22q13 Deletion Syndrome (Phelan-McDermid Syndrome)” (Easily Confused)
The similarly named “22q13 deletion syndrome (Phelan-McDermid syndrome)” is caused by the 22q13 region being “lost,” which is a different cause and a different symptom pattern from the “duplication” (extra copy) condition covered in this article. When comparing test results or article titles, first check whether the finding is a “deletion” or a “duplication.”
| Comparison | 22q13 Duplication Syndrome (this article) | 22q13 Deletion Syndrome (Phelan-McDermid Syndrome) |
|---|---|---|
| Chromosomal change | Extra copy of the 22q13 region (duplication) | Loss of the 22q13 region (deletion) |
| Effect on SHANK3 | Believed to involve overexpression | Mainly reduced function (haploinsufficiency) |
| Typical symptoms | Very wide range, from mild to severe, with large individual variation | Low muscle tone, severe speech delay, autistic tendencies |
| Association with autism spectrum disorder | Seen in only some reported cases (see below) | Seen in nearly all reported cases |
| Number of reported cases | Fewer reported cases than the deletion form | Over 2,200 cases reported worldwide |
Both conditions involve the same region of chromosome 22, but whether the region is “duplicated” or “lost” changes how symptoms present. If you would like to learn more about Phelan-McDermid syndrome, please also see the related article below.
3. Main Symptoms (Wide Individual Variation)
Symptoms of 22q13 duplication syndrome vary enormously between individuals, and the size of the duplicated region alone cannot reliably predict severity. Based on reports published in medical journals, the table below summarizes the symptoms most commonly described.
| Reported symptom | General description |
|---|---|
| Developmental delay / intellectual disability | Delayed language and motor development; mild to moderate intellectual disability |
| Distinctive facial features | Short stature, small head circumference, wide-set eyes (hypertelorism), cleft lip/palate, among other features |
| Behavioral characteristics | Autism-spectrum-like behavior, hyperactivity, repetitive or restricted behaviors |
| Speech and articulation issues only | Some reported cases show only articulation or language delay, without intellectual disability |
A case report in the journal Psychiatric Genetics described a mother and son who shared the same duplication involving SHANK3. The mother had neither intellectual disability nor autism spectrum disorder, and her only symptom was a persistent articulation and language issue. Even with an identical duplication, symptom severity can differ this dramatically between family members.
A separate journal report reviewing 28 patients with a 22q13.33 duplication involving SHANK3 found intellectual disability in 14, mild distinctive facial features in 15, behavioral problems in 7, autism spectrum disorder in 5, and speech delay in 4 of the patients. In contrast to the deletion form, where autism-spectrum-like traits are seen in nearly every case, the duplication form shows these traits in only a subset of patients. What matters is not the size of the duplication itself, but which genes are involved and in what dosage.
4. Causes and Inheritance Pattern (De Novo, Familial Transmission, and Unaffected Carriers)
In addition to cases arising as a spontaneous (de novo) change, a relatively large number of cases are inherited from one parent, and in some families the parent or other relatives carrying the duplication show no noticeable symptoms at all.
De novo (spontaneous) cases
A duplication can occur by chance during the formation of sperm or egg cells, or during early cell division shortly after fertilization. It is never caused by anything the mother did during pregnancy — diet, exercise, stress, or medication use. It is a spontaneous event, and it is no one’s fault.
Balanced structural rearrangements (translocations or inversions) inherited from a parent
A case report in Molecular Syndromology described that cases where one parent carries a balanced translocation or inversion (a rearrangement where chromosome segments are moved or flipped, but with no net gain or loss of material) are reported more often than purely spontaneous cases. In this report, a mother who was an unaffected carrier of a balanced inversion (with no duplication herself) had two children who each inherited an unbalanced chromosome arrangement involving the same duplication, and both children had relatively mild symptoms.
On the other hand, as in the mother-and-son case discussed above, there are also cases where a parent who carries the duplication itself has mild symptoms and passes it on to a child. In other words, both of the following patterns have been reported: (1) an unaffected carrier of a balanced structural rearrangement having a child with an unbalanced duplication, and (2) a parent who carries the duplication itself, with mild symptoms, passing it on to a child.
In my own clinical experience, I have met families who, after a chromosomal duplication was found, asked “Did we cause this?” or “What does this mean for our next child?” Simply knowing the results of both parents’ chromosome testing can make it easier to plan for a future pregnancy. If you are concerned about the impact on a future child, genetic counseling with a certified clinical geneticist or genetic counselor is worth considering.
5. Relationship With Prenatal Testing and NIPT
Standard basic NIPT screens mainly for numerical changes in chromosomes — trisomy 21, 18, and 13 — and does not include microduplications such as 22q13 duplication. Even expanded NIPT panels that cover microdeletions and microduplications differ by testing company and plan as to whether this specific region is named and included.
Relatively common and well-known microdeletions such as 22q11.2 deletion syndrome are often included in expanded panels, whereas many microduplications, including 22q13 duplication syndrome, require checking each testing company’s specific coverage list. Please confirm in advance which regions the plan you are considering actually covers.
At Hiroclinic NIPT, we sometimes receive questions such as, “What should we do if an expanded test flags a duplication in a region we have never heard of?” The first thing to understand is that NIPT is only a non-definitive screening test.
The Japan Society of Obstetrics and Gynecology’s guidance on NIPT also states that NIPT results remain within the scope of screening (non-definitive) testing. It is also known that as the range of microdeletions and microduplications covered expands, the positive predictive value — the proportion of positive results that turn out to reflect an actual condition — tends to decrease. Even the type of chromosomal change itself cannot be determined precisely, including whether it is a “deletion” or a “duplication,” without a definitive diagnostic test.
If an expanded NIPT panel returns a positive finding for a microduplication, the typical next steps are as follows. First, genetic counseling to understand what the result means. Then, a decision on whether to proceed with chromosomal microarray analysis (CMA) using a sample obtained through amniocentesis. Please take the time to work through each step with a specialist rather than rushing to a conclusion.
6. Steps to a Definitive Diagnosis
Chromosomal microarray analysis (CMA), a detailed genetic test, plays the central role in reaching a definitive diagnosis.
Chromosomal microarray analysis (CMA)
This test can detect minute duplications on the scale of hundreds of kilobases to a few megabases — changes too small to be seen with traditional microscope-based chromosome analysis (G-banding). It can precisely determine the exact boundaries of the duplicated region and whether SHANK3 is included. For more on how amniocentesis relates to microarray testing, see our article on microarray testing via amniocentesis.
FISH, G-banding, and parental testing
FISH (fluorescence in situ hybridization), which lights up a specific chromosomal region, is used to narrow down and confirm the presence of a duplication. G-banding can only detect the duplication if it is 2 Mb or larger and the banding resolution is sufficiently high. Blood tests for both parents can also determine whether the duplication is de novo or was inherited from a parent carrying a balanced structural rearrangement.
Postnatal evaluation
After diagnosis, a combination of developmental assessment, speech and articulation evaluation, hearing tests, and, as needed, cardiac or renal ultrasound is used to build a complete picture of the child’s condition.
7. Treatment and Support (Early Intervention and Symptom-Based Care)
There is currently no cure that reverses the duplication itself, but early intervention combined with care tailored to each child’s symptoms can substantially improve quality of life.
Early intervention and rehabilitation
Once diagnosed, starting early intervention (developmental support) as soon as possible, tailored to the child’s symptoms, is recommended. Physical therapy (PT) supports posture and walking for children with delayed motor development, while occupational therapy (OT) helps with fine motor skills and sensory integration. Speech-language therapy (SLT) is adjusted to each child’s level, from mild speech delay to significant difficulty with spoken language. For more on how to approach behavioral characteristics, see our article on the relationship between NIPT and developmental disorders.
Managing milder cases
- Speech/articulation issues only: Articulation training led by a speech-language therapist, with continued monitoring after starting school.
- Behavioral characteristics: For repetitive behaviors or hyperactivity, environmental adjustments are made in coordination with early-intervention facilities and schools.
Because the range of symptoms is so wide, regular developmental assessments are essential to identify exactly what support each child needs at any given time.
Everyday considerations
Because the level of support needed varies so much depending on symptom severity, it helps to focus less on “how does my child compare to others” and more on “how has my child changed compared to last month.” What matters is your child’s own progress, not comparison with others. Keeping records from regular developmental assessments also makes conversations with your child’s doctor and therapy team much smoother.
8. Prognosis and Outlook
Because the combination and severity of symptoms vary so much between individuals, no single long-term outlook applies to everyone. Outcomes range from children with only mild speech delay to those with more noticeable developmental delay.
This individual variation is really the starting point for understanding the condition. The duplication itself is not a progressive condition, and many patients reach adulthood, supported by family and caregivers, while continuing to build on the gains made through early intervention. Research is ongoing worldwide into how the amount of SHANK3 duplication affects neurodevelopment.
9. Support for Families and Planning Future Pregnancies
The isolation that comes with a rare condition can feel overwhelming, but there are multiple places to turn, including genetic counseling and patient support groups.
It may be difficult to find another family nearby dealing with the same condition. Even so, you can still connect through domestic and international chromosomal-condition family associations and online communities to exchange information. In my view, the medical management is best left to doctors and therapy teams, while a family’s role is to celebrate each small step of progress alongside their child.
A diagnosis is not a “label” — it is a “map” that helps you understand your child more deeply and provide the right kind of support. Precisely because this condition has such a wide range of presentations, paying close attention to your own child’s specific situation is the most direct way to find what will genuinely help. Take things at your child’s own pace, without rushing, and value each day as it comes.
If you would like to learn more about the easily confused Phelan-McDermid syndrome (22q13 deletion syndrome), please see the related article below.
If you are concerned about microdeletions and microduplications in general, our article on the risks associated with small chromosomal changes may also be helpful.
If you are considering NIPT for a future pregnancy, the extent of microdeletion and microduplication coverage will affect which plan is right for you. If you are not sure which plan suits your situation, try our Plan Finder. Phone consultations are also available; please feel free to call 0120-169-629.
Frequently Asked Questions
What is 22q13 duplication syndrome?
It is a chromosomal condition caused by an extra copy (duplication) of the 22q13 region on the long arm of chromosome 22. A duplication involving the SHANK3 gene is thought to be involved, and it can affect development and behavior in various ways.
Is this different from 22q13 deletion syndrome (Phelan-McDermid syndrome)?
Yes, it is a different condition. The duplication syndrome discussed in this article is caused by an extra copy of the 22q13 region, while the deletion syndrome (Phelan-McDermid syndrome) is caused by the loss of the same region. Since the cause and typical symptoms differ, please confirm whether your test result describes a “duplication” or a “deletion.”
Can 22q13 duplication syndrome be detected by NIPT?
It is not included in standard basic NIPT (trisomy 21, 18, and 13). Even expanded panels that cover microdeletions and microduplications vary by testing company and plan as to whether this specific region is included by name. Because NIPT is a non-definitive test, a positive finding must be confirmed with a definitive diagnostic test such as amniocentesis.
Is it hereditary? Could it affect a future child? Are there unaffected carriers?
In addition to spontaneous (de novo) cases, a relatively large proportion are inherited from one parent. Some unaffected carriers of a balanced translocation or inversion have children with an unbalanced duplication, while in other cases a parent who carries the duplication itself has only mild symptoms and passes it on to a child. If you are concerned about the impact on a future child, genetic counseling is worth considering.
What tests provide a definitive diagnosis?
Chromosomal microarray analysis (CMA) is the main diagnostic tool. It can detect minute duplications that traditional microscope-based testing would miss, and results can be confirmed further with FISH testing or parental testing as needed.
How severe are the symptoms? Are there cases close to typical development?
This condition has an extremely wide range of severity. Journal reports have described cases with only articulation or language issues and no intellectual disability or autism spectrum disorder, while other cases show more noticeable developmental delay. The size of the duplication alone cannot reliably predict severity.
Medical supervision: Hiroshi Oka — Director-General, Hiroclinic (Fukubi-kai Medical Corporation), Laboratory Director. Graduate of Keio University School of Medicine. Licensed physician in both Japan and the United States, and holder of a medical doctorate. He is one of a small number of physicians in Japan to hold a Laboratory Director qualification. This article was prepared in line with medical advertising guidelines, referencing the US NIH Genetic Testing Registry (GTR), case reports published in Molecular Syndromology and Psychiatric Genetics, and guidance from the Japan Society of Obstetrics and Gynecology. Reported case counts and frequencies vary between sources due to the limited number of published cases; please consult your physician for decisions about diagnosis and treatment.
日本皮膚科学会 皮膚科専門医／日本医師会 産業医／東京衛生検査所 指導監督医
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