If you have heard the diagnosis “13q14 deletion syndrome” alongside the word “retinoblastoma,” you may be feeling uncertain about what these terms mean.
Here is the short answer: 13q14 deletion syndrome is an extremely rare genetic condition caused by the congenital loss of part of the genetic material at band 14 on the long arm of chromosome 13 (13q14). This region contains the RB1 gene, which normally suppresses a childhood eye cancer called retinoblastoma, so depending on how much is deleted, this condition carries a risk of retinoblastoma that sets it apart from most other microdeletion syndromes.
This article walks through the chromosomal change behind the condition, the relationship between the RB1 gene and retinoblastoma, how it differs from similarly named conditions, inheritance patterns, its relationship to prenatal diagnosis and NIPT, and treatment and family support. Everything here is based on information from public agencies and peer-reviewed literature, so let’s go through it step by step rather than relying on fragments of information.
💡 What this article covers
- What kind of chromosomal change 13q14 deletion syndrome is, and its relationship to the RB1 gene
- How symptoms — including development, intellectual disability, and facial features — vary with the size of the deletion
- The risk of retinoblastoma (eye cancer) and the early warning signs to watch for
- How this condition differs from “distal 13q deletion syndrome” and “trisomy 13 (Patau syndrome)”
- Inheritance patterns (de novo mutation vs. familial transmission) and what they mean for future children
- When this condition is, and is not, covered by prenatal diagnosis and NIPT
- Treatment approaches after diagnosis and the support options available to families
1. What Is 13q14 Deletion Syndrome? (The Chromosomal Change and the RB1 Gene)
This condition occurs when genetic material at band 14 on the long arm of chromosome 13 — “13q14” — is missing from birth. This region contains the RB1 gene, a tumor-suppressor gene.
The size of the deletion varies from person to person. The academic literature classifies it as follows.
| Deletion size | Approximate range | Reported tendency |
|---|---|---|
| Small deletion | Within 13q14, under 6 Mb | Tendency toward slower motor and language development |
| Medium deletion | 13q12.3–q21.2, 6–20 Mb | Mild to moderate psychomotor developmental delay |
| Large deletion | 13q12–q31.2, over 20 Mb | Psychomotor developmental delay ranging from mild to severe |
This classification is based on a peer-reviewed study of patients with 13q14 deletions involving the RB1 gene. It is also listed in the European rare disease database Orphanet under registration number “ORPHA:1587” as an extremely rare disorder. Case reports are limited, so the exact incidence has not yet been established.
Roughly one in ten cases of hereditary retinoblastoma is caused by a chromosomal deletion involving the RB1 gene like this one, while most of the rest are caused by small mutations (point mutations) within the gene itself. Even though both fall under “RB1 abnormalities,” how much the deletion affects areas beyond the eye depends heavily on its size — a key point for understanding this condition.
2. Main Symptoms (Development, Intellectual Disability, and Facial Features)
The degree of developmental delay and intellectual disability varies widely depending on the size of the deletion, and distinctive facial features may also be present. The study referenced above (covering seven patients) reported the following frequencies of facial features.
| Facial feature | Reported frequency |
|---|---|
| Broad forehead | 6 of 7 patients (about 86%) |
| Prominent philtrum (groove below the nose) | 5 of 7 patients (about 71%) |
| Frontal bossing, thick eyebrows, deep-set eyes | 3 of 7 patients (about 43%) |
| Depressed or broad nasal bridge | 2 of 7 patients (about 29%) |
In this study, three of the seven patients showed no reported developmental delay, while four had severe psychomotor developmental delay. In other words, even among cases that all involve a “13q14-containing deletion,” how the condition presents can differ substantially from person to person.
- Developmental delay: Motor milestones such as head control and walking may progress at a slower pace.
- Intellectual disability: Depending on the size of the deletion, this can range from no reported impairment to mild, moderate, or severe intellectual disability.
- Retinoblastoma risk: When the RB1 gene is included in the deletion, the child has a congenitally elevated risk of developing this childhood eye cancer during infancy (covered in detail in the next section).
- Organ abnormalities: Abnormalities of the heart, kidneys, and other organs have been reported in some cases.
For a broader picture of intellectual disability and developmental traits across chromosomal conditions, see our article on what NIPT reveals about intellectual disability.
3. Retinoblastoma (Eye Cancer) Risk and Early Warning Signs
When a deletion includes the RB1 gene, the child has a congenitally elevated risk of developing retinoblastoma during infancy, which makes regular ophthalmologic screening for early detection essential.
Why the Risk Increases (The Two-Hit Hypothesis)
The RB1 gene is normally a tumor-suppressor gene that prevents cells from becoming cancerous. A child with 13q14 deletion syndrome is already missing one copy of the RB1 gene (the “first hit”) from birth. If a retinal cell then acquires an acquired change in its remaining RB1 copy (the “second hit”), that cell can become cancerous, giving rise to retinoblastoma. This concept is known as the “two-hit hypothesis” and is described in GeneReviews Japan’s overview of retinoblastoma (Japanese-language source).
Because these children already carry the first hit from birth, the second, ordinarily rare change is more likely to occur independently in both eyes or at multiple sites. This is why hereditary retinoblastoma is more often bilateral (affecting both eyes) than the non-hereditary form.
Early Warning Signs
According to Japan’s national database for pediatric chronic diseases, the Center for Pediatric Chronic Disease Information (Japanese-language source), 95% of retinoblastoma cases are diagnosed by age 5, with an average age at onset of 18 months. The most common initial sign is leukocoria — a white or glowing appearance of the pupil, sometimes first noticed in a flash photograph — accounting for 60% of cases, followed by strabismus (misaligned eyes) at 13%, with conjunctival redness at 5% and decreased vision at 2%.
For a child already diagnosed with 13q14 deletion syndrome, regular dilated fundus examinations — even before any symptoms appear — increase the chance of detecting retinoblastoma before signs such as leukocoria develop. Work with a pediatric ophthalmologist to determine the right screening interval for your child.
Lifelong Follow-Up After Treatment
In hereditary retinoblastoma (where the RB1 change is present in the germline), the risk of second cancers outside the eye — such as osteosarcoma, soft-tissue sarcoma, and malignant melanoma — remains elevated well into adulthood. This risk rises further in patients who received external-beam radiation therapy, which is why lifelong follow-up is recommended.
Rather than assuming “treatment is over, so we’re in the clear,” it’s important to keep up regular checkups into adulthood to protect long-term health.
4. How It Differs From Similarly Named Conditions (Distal 13q Deletion Syndrome and Trisomy 13)
Sharing the number “13” and the word “deletion” does not mean these are the same disease — what matters is exactly which part of the chromosome is affected and how. Here is how 13q14 deletion syndrome compares to two conditions it’s easily confused with.
| Comparison | 13q14 Deletion Syndrome (this article) | Distal 13q Deletion Syndrome | Trisomy 13 (Patau Syndrome) |
|---|---|---|---|
| Type of change | Loss of part of chromosome 13 (structural) | Loss of the distal end of chromosome 13 (structural) | An extra copy of chromosome 13 (numerical) |
| Main region affected | Near band q14 of the long arm; often includes the RB1 gene | Beyond band q31 of the long arm (the terminal region); includes genes such as ZIC2 and EFNB2 | Not a deletion of a specific region — a numerical chromosome abnormality |
| Distinctive risk | Retinoblastoma (eye cancer) | Holoprosencephaly, limb malformations | Severe heart and brain complications, multiple congenital anomalies |
“Distal 13q deletion syndrome,” which involves loss of the far end of the chromosome (beyond 13q31), includes genes such as ZIC2 that are involved in the separation of the left and right sides of the brain, and centers on holoprosencephaly and limb malformations — a distinctly different condition from the one covered in this article. You can read more in our guide to distal 13q deletion syndrome. Note that when a deletion is very large and extends all the way to 13q14, features of both conditions can overlap.
“Trisomy 13 (Patau syndrome),” on the other hand, is a numerical abnormality in which chromosome 13 is present in three copies instead of two — a fundamentally different mechanism from 13q14 deletion syndrome. Be careful not to apply information about one condition to the other simply because a report mentions the number “13.”
5. Cause and Inheritance Pattern (De Novo Mutation and Familial Transmission)
Most cases arise from a spontaneous (de novo) mutation, but in rare instances a parent carries a balanced translocation, which raises the recurrence risk for siblings.
De Novo (Spontaneous) Cases
Occasionally, a chance copying error occurs during the formation of sperm or egg cells, or during the earliest cell divisions after fertilization. This is not caused by anything in the mother’s diet or lifestyle during pregnancy. There is no reason to blame yourself.
Parental Balanced Translocation and Recurrence Risk
According to a case report on 13q deletion syndrome arising from a paternal balanced translocation, while most cases occur as spontaneous de novo mutations, in rare instances one parent carries a “balanced translocation” — a rearrangement of chromosomal material that causes no symptoms in the parent themselves. In these cases, the recurrence risk for siblings can be as high as 50%, and the report notes that a portion of apparently de novo cases (around 2% in the cited series) may in fact stem from an undetected parental translocation.
For this reason, the same paper recommends routine parental chromosome testing (karyotyping) and FISH analysis for every family in which 13q deletion syndrome has been diagnosed. Knowing the parents’ results makes it much easier to plan for future pregnancies. If you’re concerned about the impact on a future child, consider genetic counseling with a certified clinical geneticist or genetic counselor.
6. Relationship to Prenatal Diagnosis and NIPT
13q14 deletion syndrome is not covered by standard NIPT panels; it can only come up as a candidate finding through an expanded panel that screens for microdeletions — and even then, it is extremely rare.
Standard NIPT mainly screens for changes in the “number” of chromosomes — trisomy 21, 18, and 13. Here, “13” refers to trisomy 13, an extra copy of the whole chromosome, which is an entirely different type of change from the “partial deletion” at 13q14 described in this article. A negative result for trisomy 13 on standard NIPT does not rule out 13q14 deletion syndrome.
At Hiro Clinic NIPT, we sometimes hear from patients who ask, “What should I do if an expanded microdeletion panel flags a region I’ve never heard of?” The first thing to understand is that NIPT is only a non-definitive screening test.
Guidance from the Japan Society of Obstetrics and Gynecology on NIPT (Japanese-language source) states that NIPT results remain within the scope of screening and are not a definitive diagnosis. A definitive diagnosis requires chromosomal microarray analysis (CMA) on a sample obtained through amniocentesis. It is also well recognized that as a microdeletion panel expands to cover more regions, the positive predictive value — the proportion of positive results that reflect a true underlying condition — tends to decrease.
If NIPT returns a positive finding for a microdeletion involving 13q14, the typical path forward is as follows. First, genetic counseling to clarify what the result means. From there, you and your partner decide together whether to pursue CMA via amniocentesis for a definitive diagnosis. If involvement of the RB1 gene is suspected, it also helps to confirm the plan for ophthalmologic follow-up after birth. Rather than rushing to a conclusion, work through each step with a specialist.
7. The Path to a Confirmed Diagnosis
Chromosomal microarray analysis (CMA) plays the central role in confirming the diagnosis, and an ophthalmologic evaluation is also carried out after birth.
Chromosomal Microarray Analysis (CMA)
This test can detect deletions on the scale of hundreds of kilobases to several megabases — far smaller than what conventional microscope-based karyotyping (G-banding) can find. It reveals exactly where a deletion begins and ends, and whether the RB1 gene is included.
FISH Analysis and Parental Testing
FISH analysis, which lights up a specific chromosomal region for confirmation, is sometimes used to support the diagnosis. Testing the parents’ blood alongside this can determine whether the deletion arose de novo or stems from a parental balanced translocation.
Postnatal Evaluation (Including Ophthalmologic Assessment)
After diagnosis, the child’s overall condition is assessed through a combination of developmental testing, evaluation of the heart, kidneys, and other organs, and — when RB1 involvement is suspected — a fundus examination by a pediatric ophthalmologist.
Treatment
There is currently no way to restore the missing piece of chromosome, but combining developmental support with active management of retinoblastoma risk can help each child grow and thrive.
- Developmental support and therapy: Physical therapy (PT), occupational therapy (OT), and speech-language therapy (ST) are used to support motor, language, and daily-living development.
- Retinoblastoma treatment: When preserving the eye is possible, options include systemic chemotherapy, laser therapy, thermotherapy, local intra-arterial chemotherapy (such as melphalan), and intravitreal injection; in more advanced cases, enucleation (surgical removal of the eye) followed by chemotherapy may be chosen instead.
- Organ management: When heart or kidney abnormalities are present, ongoing management by the relevant specialist is needed.
- Lifelong follow-up: Because the risk of second cancers persists into adulthood in hereditary retinoblastoma, regular checkups should continue well beyond childhood.
Because the combination and severity of symptoms differ from child to child, there is no single fixed course that “always” happens with this condition. A pediatrician, pediatric ophthalmologist, and developmental support staff typically work together to build a support plan tailored to your child, one step at a time.
Prognosis
Outcomes range from children with little noticeable developmental delay to those who need long-term support, and quality of life is shaped largely by early intervention and early detection and treatment of retinoblastoma.
With appropriate support and medical management, quality of life can generally be expected to improve, though prognosis varies from person to person depending on the size of the deletion, whether the RB1 gene is involved, and the presence of other complications. Because retinoblastoma detected early offers more treatment options, both early developmental support and regular ophthalmologic screening matter a great deal.
Burden on Parents and Support for Families
Because long-term therapy and medical management are often needed, families frequently face financial and emotional strain — and having a connection to specialized support organizations can make a real difference.
It may be hard to find another family nearby raising a child with the same condition. Even so, you can still connect with other families affected by chromosomal rare diseases and draw on the specialized support genetic counseling can offer. Medical management is best left to your doctors and developmental support staff — a family’s role, we believe, is to celebrate each small step of your child’s progress together. Working with local support services and specialized medical institutions to build out that support system matters a great deal.
If you’d like to learn about other microdeletion syndromes as well, the articles below may help.
If you’re concerned about microdeletions in general, our article on the risks of subtle chromosomal abnormalities is also worth reading.
If you’re considering NIPT for a future pregnancy, how far you extend microdeletion coverage will affect which plan is right for you. If you’re not sure which plan fits your needs, try our plan finder. Phone consultations are also welcome — feel free to call 0120-169-629 with any questions.
Frequently Asked Questions
Are 13q14 deletion syndrome and “distal 13q deletion syndrome” the same condition?
No, they are distinct conditions. Both involve a deletion on the long arm of chromosome 13, but the condition in this article affects the region near q14 (which often includes the RB1 gene), while distal 13q deletion syndrome affects the terminal region beyond q31 (which includes genes such as ZIC2 and EFNB2). The genes involved and the main symptoms differ between the two, so a chromosomal microarray test is used to confirm the exact deletion range.
Is 13q14 deletion syndrome the same as trisomy 13 (Patau syndrome)?
No. Trisomy 13 is a numerical abnormality in which chromosome 13 is present in three copies. 13q14 deletion syndrome is a structural abnormality involving the loss of part of a chromosome — the two conditions arise through entirely different mechanisms.
Will a child with this condition definitely develop retinoblastoma?
Not necessarily. When the deletion includes the RB1 gene, the child has a congenitally elevated risk, but whether retinoblastoma actually develops depends on whether an additional, acquired change occurs in a retinal cell. Given this risk, regular fundus examinations are recommended to support early detection.
Can NIPT detect 13q14 deletion syndrome?
It is not covered by standard NIPT panels; it can only come up as a candidate finding through an expanded panel that screens for microdeletions, and even then it is extremely rare. Because NIPT is a non-definitive test, a positive finding requires confirmation through a definitive test such as chromosomal microarray analysis (CMA) via amniocentesis.
Is this condition hereditary? Could it affect a future child?
Most cases arise from a spontaneous (de novo) mutation, and the recurrence risk for a future child is generally low. However, in rare cases where one parent carries a balanced translocation, the recurrence risk for siblings can be as high as 50%, so parental chromosome testing is recommended to check for this.
What test provides a definitive diagnosis?
Chromosomal microarray analysis (CMA) is the primary diagnostic test. It can detect subtle deletions that conventional microscope-based testing would miss, with FISH analysis and parental testing used for confirmation when needed.
Medical supervision: Dr. Hiroshi Oka — Director-in-Chief and Lab Director, Hiro Clinic (Fukumikai Medical Corporation). A graduate of Keio University School of Medicine, Dr. Oka holds a Ph.D. in Medicine and has passed the national medical licensing examinations of both Japan and the United States. He is one of the few physicians in Japan to hold laboratory director credentials. This article was prepared in line with Japan’s medical advertising guidelines, drawing on public and academic sources including Orphanet, the Center for Pediatric Chronic Disease Information, GeneReviews Japan, and the Japan Society of Obstetrics and Gynecology. Because case numbers for this rare disease are limited, reported frequencies and figures vary across the literature. 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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