GENE GUIDE

KMT2A-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated on 2024. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has KMT2A-Related Syndrome.
a doctor sees a patient

KMT2A-related syndrome is also called Wiedemann-Steiner syndrome (WDSTS). For this webpage, we will be using the name KMT2A-related syndrome to encompass the wide range of variants observed in the people identified. 

KMT2A-related syndrome happens when there are changes in the KMT2A gene. These changes can keep the gene from working as it should. 

Key Role

The KMT2A gene plays a key role in how the brain and body develop. 

Symptoms

Because the KMT2A gene is important in the development of the brain and the body, many people who have KMT2A-related syndrome have: 

  • Developmental delay 
  • Intellectual disability 
  • Difficulty eating 
  • Slow growth 
  • Short height 
  • Extra hair growth on the body 
  • Low muscle tone 
  • Movement issues 
  • Speech delay 
  • Features of autism 
  • Aggressive behavior

KMT2A-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 KMT2A 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 KMT2A plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that KMT2A-related syndrome is often the result of a de novo variant in KMT2A. Many parents who have had their genes tested do not have the KMT2A genetic variant found in their child who has the syndrome. In some cases, KMT2A-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

KMT2A-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in KMT2A they will likely have symptoms of KMT2A-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

GENE / gene
GENE / gene
Genetic variant that happens in sperm or egg, or after fertilization
GENE / gene
Child with de novo genetic variant
gene / gene
Non-carrier child
gene / gene
Non-carrier child

Why does my child have a change in the KMT2A gene?

No parent causes their child’s KMT2A-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.

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 KMT2A-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 KMT2A-related syndrome, the sibling’s risk of having a child who has KMT2A-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing KMT2A-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit KMT2A-related syndrome. 

As of 2024, over 180 people with KMT2A-related syndrome have been reported in medical research. 

People who have KMT2A-related syndrome may look different. Appearance can vary and can include some but not all of these features: 

  • Droopy eyelids 
  • Thick eyebrows 
  • Long eyelashes 
  • Wide-set eyes

Scientists and doctors have only just begun to study KMT2A-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:

  • 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 KMT2A-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 published articles. It highlights how many people have different symptoms. To learn more about the article, see the Sources and References section of this guide.

Speech and learning  

Most people with KMT2A-related syndrome had developmental delay and/or intellectual disability. Some people had speech delay.  

  • 59 out of 67 people had developmental delay or intellectual disability (88 percent) 
  • 5 out of 6 people had speech delay (83 percent)

Behavior 

People with KMT2A-related syndrome had behavioral issues, including autism, aggression, hyperactivity, attention-deficit/hyperactivity disorder (ADHD), or self-injurious behavior. 

  • 8 out of 13 people had other behavioral issues (62 percent) 
  • 4 out of 62 people had autism (7 percent) 
  • 4 out of 51 people had aggression (8 percent)
  • 5 out of 51 people had hyperactivity (10 percent)
62%
8 out of 13 people had other behavioral issues.
7%
4 out of 62 people had autism.
8%
4 out of 51 people had aggression.
10%
5 out of 51 people had hyperactivity.

Brain 

Some people with KMT2A-related syndrome had seizures, low muscle tone (hypotonia), or brain changes seen on magnetic resonance imaging (MRI). The most common brain changes were anormal corpus callosum and delayed myelination. Some people had sleep issues and a smaller than average head size (microcephaly).  

  • 14 out of 63 people had seizures (22 percent) 
  • 16 out of 63 people had hypotonia (25 percent)
  • 15 out of 41 people had brain changes seen on MRI (37 percent)
Human head showing brain outline
22%
14 out of 63 people had seizures.
25%
16 out of 63 people had hypotonia.
37%
15 out of 41 people had brain changes seen on MRI.

Feeding and digestion issues 

Some people had constipation or feeding issues.  

  • 2 out of 51 people had constipation (4 percent) 
  • 12 out of 51 people had feeding issues (24 percent) 

Hair findings 

People with KMT2A-related syndrome had more hair on their elbows, lower back, and lower limbs. 

  • 25 out of 51 people had more hair on their elbows (49 percent) 
  • 36 out of 51 people had more hair on their lower back (71 percent) 
  • 28 out of 51 people had more hair on their lower limbs (55 percent) 

Musculoskeletal issues 

Many people with KMT2A-related syndrome had short height. Other less common defects were dental changes and bone structure defects, such as changes in the spine structure or toes. 

  • 42 out of 51 people had short height (82 percent) 

Other medical features 

People with KMT2A-related syndrome had heart structure defects and less commonly kidney defects present at birth. Heart defects included patent ductus arteriosus, patent foramen ovale, and atrial septal defect.

Where can I find support and resources?

Wiedemann-Steiner Syndrome Foundation

Wiedemann-Steiner Syndrome will be understood globally and all those diagnosed will reach their greatest potential.

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.”

Sources and References

The content in this guide comes from published studies about KMT2A-related syndrome. Below you can find details about the studies.

  • di Bari, I., Ceccarini, C., Curcetti, M., Cesarano, C., Croce, A. I., Adipietro, I., Gallicchio, M. G., Palladino, G. P., Patrizio, M. P., … & Margaglione, M. (2024). Uncovering a genetic diagnosis in a pediatric patient by whole exome sequencing: A modeling investigation in Wiedemann-Steiner syndrome. Genes (Basel), 15(9), 1155. https://pubmed.ncbi.nlm.nih.gov/39336746/
  • Di Fede, E., Massa, V., Augello, B., Squeo, G., Scarano, E., Perri, A. M., Fischetto, R., Causio, F. A., Zampino, G., … & Gervasini, C. (2021). Expanding the phenotype associated to KMT2A variants: Overlapping clinical signs between Wiedemann-Steiner and Rubinstein-Taybi syndromes. European Journal of Human Genetics, 29(1), 88-98. https://pubmed.ncbi.nlm.nih.gov/32641752/ 
  • Lin, Y., Chen, X., Xie, B., Guan, Z., Chen, X., Li, X., Yi, P., Du, R., Mei, H., … & Zeng, C. (2023). Novel variants and phenotypic heterogeneity in a cohort of 11 Chinese children with Wiedemann-Steiner syndrome. Frontiers in Genetics, 14, 1085210. https://pubmed.ncbi.nlm.nih.gov/37025457/
  • Prada, E., Meossi, C., Marafon, D. P., Grilli, F., Scuvera, G., Marchisio, P. G., Agostoni, C. V., Natacci, F., & Milani, D. (2024). The overlapping of phenotypes in Wiedemann-Steiner, Kleefstra and Coffin-Siris syndromes: A study of eleven patients. Italian Journal of Pediatrics, 50(1), 187. https://pubmed.ncbi.nlm.nih.gov/39294711/
  • Sahly, A. N., Srour, M., Buhas, D., Scheffer, I. E., & Myers, K. A. (2023). The epileptology of Wiedemann-Steiner syndrome: Electroclinical findings in five patients with KMT2A pathogenic variants. European Journal of Paediatric Neurology, 44, 46-50. https://pubmed.ncbi.nlm.nih.gov/37075569/

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