5q35 Deletion Syndrome

Table of contents
- What is 5q35 deletion syndrome?
- Key Role
- Symptoms
- What causes 5q35 deletion syndrome?
- Why do I or my child have 5q35 deletion syndrome?
- What are the chances that other family members or future children will have 5q35 deletion syndrome?
- How many people have 5q35 deletion syndrome?
- Do people who have 5q35 deletion syndrome look different?
- How is 5q35 deletion syndrome treated?
- Behavior and development concerns linked to 5q35 deletion syndrome
- Medical and physical concerns linked to 5q35 deletion syndrome
- Where can I find support and resources?
- Sources and References
5q35 deletion syndrome is also called Sotos syndrome. For this webpage, we will be using the name 5q35 deletion syndrome to encompass the wide range of variants observed in the people identified.
What is 5q35 deletion syndrome?
5q35 deletion syndrome happens when a person has a missing piece of chromosome 5, one of the body’s 46 chromosomes. Chromosomes are structures in our cells that house our genes. The missing piece can affect learning and how the body develops.
This condition is caused by either a deletion that includes the NSD1 gene or a damaging genetic variant in the NSD1 gene.

Key Role
Genes within the 5q35 region are important for brain development and function.
Symptoms
Because genes in the 5q35 region are important in brain development and function, many people who have 5q35 deletion syndrome have:
- Developmental delay
- Intellectual disability
- Language delay
- Seizures
- Coordination problems
- Behavioral issues
- Kidney tumor, called a Wilms tumor
- Advanced bone age
- Taller than average height
- Larger than average head size
- Ear infections and hearing loss
- Heart defects
- Joint issues
- Sideways curve of the spine, also called scoliosis
- Brain changes seen on magnetic resonance imaging (MRI)
What causes 5q35 deletion syndrome?
5q35 deletion 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. Every child gets two copies of the 5q35 gene: one copy from their mother’s egg, and one copy from their father’s sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of creating the egg or sperm is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.
Sometimes a spontaneous variant happens in the sperm, egg or after fertilization. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child is usually the first in the family to have the genetic variant.
De novo variants can take place in any gene. We all have some de novo variants, most of which don’t affect our health. But because 5q35 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that 5q35 deletion syndrome is often the result of a de novo variant in 5q35. Many parents who have had their genes tested do not have the 5q35 genetic variant found in their child who has the syndrome. In some cases, 5q35 syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
5q35 deletion is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in 5q35 they will likely have symptoms of 5q35 deletion syndrome. For someone with an autosomal dominant genetic syndrome, every time they have a child there is a 50 percent chance they pass on the same genetic variant and a 50 percent chance they do not pass on the same genetic variant.
Autosomal Dominant Genetic Syndrome
Why do I or my child have 5q35 deletion syndrome?
No parent causes their child’s 5q35 deletion 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 5q35 deletion 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 5q35 deletion syndrome depends on the genes of both biological parents.
- If neither biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is on average 1 percent. This 1 percent chance is higher than the chance of the general population. The increase in risk is due to the very unlikely chance that more of the mother’s egg cells or the father’s sperm cells carry the same genetic variant.
- If one biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is 50 percent.
For a symptom-free brother or sister of someone who has 5q35 deletion syndrome, the sibling’s risk of having a child who has 5q35 deletion syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing 5q35 deletion syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit 5q35 deletion syndrome.
- If one biological parent has the same genetic variant causing 5q35 deletion syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent.
For a person who has 5q35 deletion syndrome, the risk of having a child who has the syndrome is about 50 percent.

How many people have 5q35 deletion syndrome?
As of 2025, at least 900 people with a damaging genetic variant in the NSD1 gene or a 5q35 deletion have been described in medical research. 5q35 deletion syndrome happens in about 1 in every 14,000 births.

Do people who have 5q35 deletion syndrome look different?
People with 5q35 deletion syndrome may look different. Appearance can vary and can include some but not all of these features:
- Larger than average head size
- Early appearance of teeth
- Rapid eye movements
- Brittle fingernails
- Red cheeks, also called malar flushing
- Noticeable forehead
- Long narrow face and chin
- Thinning hair in the front

How is 5q35 deletion syndrome treated?
Scientists and doctors have only just begun to study 5q35 deletion 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 5q35 deletion 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 5q35 deletion syndrome
Learning
People with 5q35 deletion syndrome had developmental delay and intellectual disability (ID), usually mild to moderate. Researchers think that people who have a deletion in the 5q35 region are more likely to have more severe learning issues compared with people who have a damaging genetic variant that affects only the NSD1 gene.
- 77 out of 85 people had developmental delay (91 percent)
- 125 out of 149 people had intellectual disability (84 percent)
The severity of intellectual disability (ID) varied among people:
- 118 out of 149 people had mild to moderate ID (79 percent)
- 7 out of 149 people had severe ID (5 percent)
- 24 out of 146 people had no ID (16 percent)

Behavior
Some people with 5q35 deletion syndrome had behavioral issues, such as autism, aggression, and sleep issues. Attention-deficit/hyperactivity disorder (ADHD) has been reported, but some researchers think that it is very uncommon in the community.
- 6 out of 91 people had autism (7 percent)
- 8 out of 31 people had ADHD (26 percent)
Brain
People with 5q35 deletion syndrome had neurological medical issues, such as lower than average muscle tone (hypotonia) and seizures. Many people had brain changes seen on magnetic resonance imaging (MRI), commonly dilated ventricles.
- 22 out of 42 people had hypotonia (52 percent)
- 55 out of 255 people had seizures (22 percent)

Medical and physical concerns linked to 5q35 deletion syndrome
Growth
People with 5q35 deletion syndrome often had overgrowth issues, including having a taller than average height, a larger than average head size (macrocephaly), and advanced bone age. Some people had skeletal defects, such as a sunken chest, spine defects, and fused or webbed fingers, as well as a sideways curve of the spine, also called scoliosis.
- 106 out of 228 people were taller than average (47 percent)
- 53 out of 62 people had macrocephaly (86 percent)
- 41 out of 55 people had advanced bone age (75 percent)
- 21 out of 45 people had skeletal defects (47 percent)
- 42 out of 131 people had scoliosis (32 percent)
Heart
People with 5q35 deletion syndrome had congenital heart defects. The most commonly reported defects were septal defects, aortic defects, patent ductus arteriosus, left ventricular non-compaction/hypertrabeculated left ventricle, and pulmonary valve defects.
About 1 in 5 people with 5q35 deletion syndrome had congenital heart defects.
- 52 out of 244 people had congenital heart defects (21 percent)

Graphs
People With 5q35 Deletion Syndrome With Congenital Heart Defects
About 1 in 5 people with 5q35 deletion syndrome had congenital heart defects.
People had various heart findings.
- 16 out of 76 people had septal defects (21 percent)
- 9 out of 45 people had aortic defects (20 percent)
- 4 out of 76 people had patent ductus arteriosus (5 percent)
- 4 out of 45 people had left ventricular non-compaction/hypertrabeculated left ventricle (9 percent)
- 6 out of 76 people had pulmonary valve defects (8 percent)

Graphs
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Other medical features
Some people had eye or vision issues, hearing loss, and kidney defects. Vision issues include crossed eyes (strabismus), farsightedness (hyperopia), uncontrolled eye movements (nystagmus), an imperfection of the eye that causes blurred distance and near vision (astigmatism), and break down of the retina (retinal atrophy).
- 26 out of 200 people had kidney defects (13 percent)

Potential tumor risk
Studies suggest that 3 percent of people (3 out of 100) with 5q35 deletion syndrome develop cancers. Various tumor types have been described.
- 4 people with sacrococcygeal teratoma, a tumor on the tailbone and the most common tumor found in newborns
- 2 people with neuroblastoma, a cancer of the nerve tissue
- 1 person with hepatoblastoma, a cancer of the liver
- 1 person with a presacral and intracranial ganglioglioma, a slow-growing benign tumor
- 1 person with acute lymphoblastic leukemia, a cancer of the blood and bone marrow
- 1 person with small-cell lung cancer, a lung cancer that typically affects people with a long-term history of smoking
- 1 person with an astrocytoma, a cancer of the brain and spinal cord
- 1 person with a pineoblastoma, a tumor in a gland in the brain
Additional studies with more people who have 5q35 deletion syndrome are needed to better understand whether this syndrome is linked to cancer, or if these instances of cancer are a coincidence.
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 5q35 deletion: www.simonssearchlight.org/research/what-we-study/5q35-deletion
- Simons Searchlight Facebook group: https://www.facebook.com/groups/5q35-deletion

Sources and References
- Calcagni, G., Ferrigno, F., Franceschini, A., Dentici, M. L., Capolino, R., Sinibaldi, L., Minotti, C., Micalizzi, A., Alesi, V., … & Digilio, M. C. (2024). Congenital heart defects in patients with molecularly confirmed Sotos syndrome. Diagnostics (Basel), 14(6), 594. doi:10.3390/diagnostics14060594
- Ha, K., Anand, P., Lee, J. A., Jones, J. R., Kim, C. A., Bertola, D. R., Labonne, J. D., Layman, L. C., Wenzel, W., & Kim, H. G. (2016). Steric clash in the SET domain of histone methyltransferase NSD1 as a cause of Sotos syndrome and its genetic heterogeneity in a Brazilian cohort. Genes (Basel), 7(11), 96. doi:10.3390/genes7110096
- Lourdes, V. H., Mario, S. C., Didac, C. A., Mercè, B., Loreto, M., Leticia, P., Lucia, F. A., Martínez-Monseny, A. F., & Mercedes, S. (2023). Beyond the known phenotype of sotos syndrome: A 31-individuals cohort study. Frontiers in Pediatrics, 11, 1184529. doi:10.3389/fped.2023.1184529
- Ocansey, S., Cole, T. R. P., Rahman, N., & Tatton-Brown, K. Sotos syndrome. 2025 Jun 5. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1479/
- Machida, M., Katoh, H., Machida, M., Miyake, A., Taira, K., & Ohashi, H. (2021). The association of scoliosis and NSD1 gene deletion in Sotos syndrome patients. Spine (Phila Pa 1976), 46(13), E726-E733. doi:10.1097/brs.0000000000003879
- Saugier-Veber, P., Bonnet, C., Afenjar, A., Drouin-Garraud, V., Coubes, C., Fehrenbach, S., Holder-Espinasse, M., Roume, J., Malan, V., … & Bürglen, L. (2007). Heterogeneity of NSD1 alterations in 116 patients with Sotos syndrome. Human Mutation, 28(11), 1098-1107. doi:10.1002/humu.20568
- Siracusano, M., Riccioni, A., Frattale, I., Arturi, L., Dante, C., Galasso, C., Gialloreti, L. E., Conteduca, G., Testa, B., … & Mazzone, L. (2023). Cognitive, adaptive and behavioral profile in Sotos syndrome children with 5q35 microdeletion or intragenic variants. American Journal of Medical Genetics Part A, 191(7), 1836-1848. doi:10.1002/ajmg.a.63211
- Vieira, G. H., Cook, M. M., Ferreira De Lima, R. L., Frigério Domingues, C. E., de Carvalho, D. R., Soares de Paiva, I., Moretti-Ferreira, D., & Srivastava, A. K. (2015). Clinical and molecular heterogeneity in Brazilian patients with sotos syndrome. Molecular Syndromology, 6(1), 32-38. doi:10.1159/000370169