SOX5-Related Syndrome
SOX5-related syndrome is also called Lamb-Shaffer syndrome. For this webpage, we will be using the name SOX5-related syndrome to encompass the wide range of variants observed in the people identified.
What is SOX5-related syndrome?
SOX5-related syndrome happens when there are changes to the SOX5 gene. These changes can keep the gene from working as it should.
Key Role
The SOX5 gene plays a key role in brain development.
Symptoms
Because the SOX5 gene is important for brain activity, many people who have SOX5-related syndrome have:
- Developmental delay
- Intellectual disability
- Speech delay
- Behavioral issues
- Low muscle tone
- Motor delay
- Developmental delay
- Vision issues
What causes SOX5-related syndrome?
SOX5-related 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 SOX5 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 SOX5 plays a key role in development, de novo variants in this gene can have a meaningful effect.
Research shows that SOX5-related syndrome is often the result of a de novo variant in SOX5. Many parents who have had their genes tested do not have the SOX5 genetic variant found in their child who has the syndrome. In some cases, SOX5-related syndrome happens because the genetic variant was passed down from a parent.
Autosomal dominant conditions
SOX5-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in SOX5 they will likely have symptoms of SOX5-related 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 does my child have a change in the SOX5 gene?
No parent causes their child’s SOX5-related syndrome. We know this because no parent has any control over the gene 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 gene 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 SOX5-related 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 SOX5-related 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 SOX5-related syndrome, the sibling’s risk of having a child who has SOX5-related syndrome depends on the sibling’s genes and their parents’ genes.
- If neither parent has the same genetic variant causing SOX5-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit SOX5-related syndrome.
- If one biological parent has the same genetic variant causing SOX5-related 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 SOX5-related syndrome, the risk of having a child who has the syndrome is about 50 percent.
How many people have SOX5-related syndrome?
As of 2026, over 100 people in the world with changes in the SOX5 gene have been described in medical research. The first case of SOX5-related syndrome was described in 2012. Scientists expect to find more people who have the syndrome as access to genetic testing improves.
Do people who have SOX5-related syndrome look different?
People with SOX5-related syndrome may look different. People are described as having distinctive facial features, but the features are quite variable.
How is SOX5-related syndrome treated?
Scientists and doctors have only just begun to study SOX5-related 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:
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- 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:
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- Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
- Guide individualized education plans (IEPs).
Specialists advise that therapies for SOX5-related 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: www.epilepsy.com/learn/types-seizures.
This section includes a summary of information from major published articles. 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 SOX5-related syndrome
Learning and Speech
Most people with SOX5-related syndrome had developmental delay and/or intellectual disability, and speech delay or impairment.
- 84 out of 86 people had developmental delay and/or intellectual disability (98 percent)
- 72 out of 72 people had speech delay or impairment (100 percent)
Behavior
Some people with SOX5-related syndrome had behavioral issues, such as autism or features of autism, attention-deficit/hyperactivity disorder (ADHD), aggressive behavior, anxiety, and oppositional behaviors.
- 73 out of 82 people had behavioral challenges (89 percent)
- 24 out of 82 people had autism (29 percent)
Brain
People with SOX5-related syndrome had low muscle tone (hypotonia), seizures, a smaller than average head size (microcephaly), sleep diagnoses, and brain changes seen on magnetic resonance imaging (MRI).
- 34 out of 76 people had hypotonia (45 percent)
- 16 out of 66 people had seizures (24 percent)
- 7 out of 63 people had microcephaly (11 percent)
- 9 out of 63 people had brain changes seen on MRI (14 percent)
Graphs
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Medical and physical concerns linked to SOX5-related syndrome
Vision
Many people with SOX5-related syndrome had vision issues, including droopy eyelids (ptosis), crossed eyes (strabismus), and optic atrophy.
- 42 out of 66 people had vision issues (64 percent)
Heart
A few people with SOX5-related syndrome had heart defects, such as mitral valve prolapse, ventricular septal defect, pulmonary stenosis, or heart murmur.
- 7 out of 66 people had heart defects (11 percent)
Where can I find support and resources?
Lamb-Shaffer Syndrome Organization
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 SOX5 – www.simonssearchlight.org/research/what-we-study/sox5
- Simons Searchlight SOX5 Facebook community – Simons Searchlight SOX5 Facebook community
Sources and references
The content in this guide comes from published studies about SOX5-related syndrome. Below you can find details about each study, as well as links to summaries or, in some cases, the full article.
- Wang, P., Xie, H., Xiao, X., Wang, H., Wang, Y., & Liu, S. (2025). Functional characterization of SOX5 variant causing Lamb-Shaffer syndrome and literature review of variants in the SOX5 gene. Orphanet Journal of Rare Diseases, 20(1), 300. doi:10.1186/s13023-025-03829-7
- Xu, J., Song, X., Zeng, L., & Zou, C. (2026). Lamb-Shaffer syndrome in a Chinese adolescent: A case report. Medicine (Baltimore), 105(10), e47820. doi:10.1097/md.0000000000047820