GENE GUIDE

TLK2-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 TLK2-Related Syndrome.
a doctor sees a patient

TLK2-related syndrome happens when there are changes to the TLK2 gene. These changes can keep the gene from working as it should.

Key Role

The TLK2 gene plays a key role in brain growth.

Symptoms

Because the TLK2 gene is important in the development and function of brain cells, many people who have TLK2-related syndrome have:

  • Developmental delay
  • Behavior issues
  • Gastrointestinal issues

Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the TLK2 gene: one copy from their mother, from the egg, and one copy from their father, from the sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of copying genes is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both.

Sometimes a random change happens in the sperm or egg. This change to the genetic code is called a ‘de novo’, or new, change. The child can be the first in the family to have the gene change.

De novo changes can take place in any gene. We all have some de novo changes, most of which don’t affect our health. But because TLK2 plays a key role in development, de novo changes in this gene can have a meaningful effect.

Research shows that TLK2-related syndrome is often the result of a de novo change in TLK2. Many parents who have had their genes tested do not have the TLK2 gene change found in their child who has the syndrome. In some cases, TLK2-related syndrome happens because the gene change was passed down from a parent. This is called dominant inheritance.

Dominant Inheritance

Children have a 50% chance of inheriting the genetic change.

Child who has genetic change in TLK2 gene

Genetic change occurs in egg or sperm after fertilization
Child with de novo genetic change in autism gene

Why does my child or I have a change in the TLK2 gene?

No parent causes their child’s TLK2-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 TLK2-related syndrome depends on the genes of both birth parents.

  • If neither birth parent has the same gene change 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 change in the gene.
  • If one birth parent has the same gene change found in their child, the chance of having another child who has the syndrome is 50 percent.

For a symptom-free sibling, a brother or sister, of someone who has TLK2-related syndrome, the risk of having a child who has the syndrome depends on the symptom-free sibling’s genes and their parents’ genes.

  • If neither parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who has TLK2-related syndrome.
  • If one birth parent has the same gene change found in their child who has the syndrome, the symptom-free sibling has a small chance of also having the same gene change. If the symptom-free sibling has the same gene change as their sibling who has the syndrome, the symptom-free sibling’s chance of having a child who has TLK2-related syndrome is 50 percent.

For a person who has TLK2-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2020, about 40 people in the world with changes in the TLK2 gene had been described in the medical literature. The first case of TLK2related syndrome was described in 2016. Scientists expect to find more people who have the syndrome as access to genetic testing improves.

Do people who have TLK2related syndrome look different?

People who have TLK2-related syndrome may look different. Appearance can vary and can include some but not all of these features:

  • Underdeveloped eyelids that cannot fully open, also called blepharophimosis
  • Wide space between the inner corners of the eyes
  • Wide tip of the nose
  • Thin upper lip

Scientists and doctors have only just begun to study TLK2-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 TLK2-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 a major published article describing 40 people who have TLK2-related syndrome. It highlights how many people have different symptoms. To learn more about the article, see the Sources and references section of this guide.

Learning

Almost three-quarters of people who have TLK2-related syndrome have intellectual disability. In most cases, this is mild. Some have language and motor delay.

  • 72 percent of people have an intellectual disability.

Behavior 

More than two-thirds have behavior issues. This includes tantrums, autism, attention deficit disorder with or without hyperactivity, and socialemotional issues.

  • 68 percent of people had behavior issues.
72%
72 percent of people have an intellectual disability.
68%
68 percent of people had behavior issues.

Feeding and digestion issues

More than one-half of people who have TLK2-related syndrome have constipation. Almost one-half have feeding issues as newborns.

  • 55 percent of people have constipation.
  • 42 percent of people have feeding issues as newborns.

Brain

Almost one-third have differences in skull shape. Almost one-quarter have a small head, also called microcephaly.

  • 31 percent of people have differences in skull shape.
  • 24 percent of people have a small head, also called microcephaly.

Growth

More than one-third are short.

  • 37 percent of people are short.

Muscle tone 

More than one-third have low muscle tone.

  • 37 percent of people have low muscle tone.

Eyes and eyesight

More than one-quarter have blurred vision. More than one-quarter have eyes that don’t point in the same direction at the same time, also called strabismus.

  • 29 percent of people have blurred vision.
  • 26 percent of people have eyes that don’t point in the same direction at the same time, also called strabismus.

Ears and hearing

About one-quarter have repeated ear infections.

  • 24 percent of people have repeated ear infections.
31%
31 percent of people have differences in skull shape.
24%
24 percent of people have a small head, also called microcephaly.
55%
55 percent of people have constipation.
42%
42 percent of people have feeding issues as newborns.
37%
37 percent of people are short.
29%
29 percent of people have blurred vision.
25%
26 percent of people have eyes that don’t point in the same direction at the same time, also called strabismus. 
24%
24 percent of people have repeated ear infections. 
35%
37 percent of people have low muscle tone. 

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.”

Sources and references

The content in this guide comes from a published study about TLK2-related syndrome. Below you can find details about the study, as well as a link to the full article.

  • Reijnders MRF. et al. American Journal of Human Genetics, 102, 1195-1203, (2018). De novo and inherited loss-of-function variants in TLK2: Clinical and genotype-phenotype evaluation of a distinct neurodevelopmental disorder www.ncbi.nlm.nih.gov/pmc/articles/PMC5992133

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