TLK2-Related Syndrome

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

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 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 TLK2-related syndrome, the sibling’s risk of having a child who has TLK2-related syndrome depends on the sibling’s genes and their parents’ genes. 

• If neither parent has the same genetic variant causing TLK2-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit TLK2-related syndrome. 
• If one biological parent has the same genetic variant causing TLK2-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 TLK2-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2026, about 103 people with TLK2-related syndrome have been identified in a medical clinic.

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.

Learning and speech

Many people with TLK2-related syndrome had intellectual disability, learning difficulties, and speech and language delay. Some people had typical intellectual development.

• 32 out of 45 people had intellectual disability and learning difficulties (71 percent)
• 41 out of 44 people had speech and language delay (93 percent)

Behavior

Some people with TLK2-related syndrome had behavioral issues, such as autism or features of autism, attention-deficit/hyperactivity disorder (ADHD), and social-emotional issues. One-third of people with TLK2-related syndrome had tantrums.

• 16 out of 47 people had autism spectrum disorder or features of autism (34 percent)
• 7 out of 42 people had ADHD (17 percent)
• 10 out of 45 people had severe social-emotional issues (22 percent)
• 14 out of 43 people had tantrums (33 percent)

Brain

Some people with TLK2-related syndrome had epilepsy, lower than average muscle tone (hypotonia), and a smaller than average head size (microcephaly). A few people had brain changes seen on magnetic resonance imaging (MRI).

• 6 out of 41 people had epilepsy (15 percent)
• 16 out of 41 people had hypotonia (39 percent)
• 11 out of 42 people had microcephaly (26 percent)
• 6 out of 41 people had brain changes on MRI (15 percent)

Vision and hearing

People with TLK2-related syndrome had eye issues, such as crossed eyes (strabismus), droopy eyelids (ptosis), and wide-set eyes. One-fourth of people had issues with recurrent ear/respiratory infections. Some people with TLK2-related syndrome had low-set ears that were rotated backwards or an underdeveloped ear shape, also known as microtia.

• 11 out of 42 people had strabismus (26 percent)
• 9 out of 41 people had ptosis (22 percent)
• 33 out of 43 people had wide-set eyes (77 percent)
• 10 out of 40 people had recurrent ear infections (25 percent)
• 14 out of 44 people had ears that were rotated backwards (32 percent)
• 12 out of 40 people had microtia (30 percent)

Mobility

One out of 5 people with TLK2-related syndrome had joint hypermobility, and some people walked on their toes.

• 8 out of 40 people had joint hypermobility (21 percent)
• 8 out of 42 people walked on their toes (19 percent)

Feeding and digestion

Some people with TLK2-related syndrome had gastrointestinal issues, such as difficulty feeding in their first month of life and constipation.

• 19 out of 43 people had early feeding difficulties (44 percent)
• 25 out of 44 people had constipation (57 percent)

Growth

People with TLK2-related syndrome were short in height and had a sideways curve of the spine, also known as scoliosis. A few people with TLK2-related syndrome were overweight or obese.

• 17 out of 43 people had short height (40 percent)
• 3 out of 40 people had scoliosis (8 percent)
• 4 out of 42 people were overweight or obese (10 percent)