The Latest Research on Kleefstra Syndrome

Why research is important

Research is vital to understanding Kleefstra Syndrome (KS). It helps doctors give better care and support, guides families with clearer answers to their many questions, and offers hope for improved treatments in the future.

At Kleefstra Syndrome UK, we know that research can feel complicated and full of technical terms. That’s why we’ve created this hub: to share the latest scientific discoveries in a way that we hope makes sense for families, while also providing links to the original publications for professionals and people who are keen to know that little bit more of the detail.

Some terminology you might see

Kleefstra Syndrome (KS1) is usually caused by a change in a gene called EHMT1, found on chromosome 9. This change means the body doesn’t make enough of an important protein (Histone Methyltransferase 1) that helps other genes work properly.

Here are some terms you might see in research papers, explained simply:

  • Genotype – your unique DNA code.

  • Phenotype – how your DNA shows up in real life (appearance, abilities, health).

  • Haploinsufficiency – when one copy of a gene doesn’t work, and the other isn’t enough on its own.

  • Null variant ❌ – a gene that doesn’t do its job at all.

  • Truncating variant ✂️ – a “shortened” gene that doesn’t work properly.

  • Carrier – someone with one faulty gene but no symptoms, who can pass it on.

  • Pathogenic variant ⚠️ – a DNA change known to cause disease.

  • Variant of unknown significance (VUS) ❓ – a gene change has been found, but doctors aren’t sure if it matters.

Most cases of KS are sporadic – meaning they happen for the first time in the child and are not inherited from parents. However, if someone has KS, they can pass it on with a 50% chance in each pregnancy.

Links to Publications

Here are recent studies from Prof. Kleefstra’s team and colleagues, with ‘plain-English’ summaries for families. Click on the links to read more:

Sleep disturbance and regression in KS

Vermeulen et al. (2017).
Sleep disturbance as a precursor of severe regression in Kleefstra Syndrome suggests a need for firm and rapid pharmacological treatment. Clinical Neuropharmacology, 40(4), 185–188.
Read More Here

Summary for families:
Some young people with KS lose skills (regression), often after severe sleep problems. This study found that quick treatment with normal doses of antipsychotic medication (rather than low, cautious doses) helped restore sleep, stopped regression, and sometimes even recovered skills.

The largest ever study of EHMT1 variants

Rots et al. (2024).
Comprehensive EHMT1 variants analysis broadens genotype-phenotype associations and molecular mechanisms in Kleefstra syndrome. American Journal of Human Genetics.
Read the paper

Summary for families:
This study looked at 209 people with EHMT1 changes. It showed that KS can look very different from person to person – from severe learning disability to normal intelligence. It also found:

  • Families can sometimes pass KS down without realising (mildly affected parents).
  • Certain genetic changes lead to milder or more severe forms.
  • The estimated frequency of KS is about 1 in 36,000 people (more common than previously thought).

Kleefstra Syndrome Type 2 (KMT2C-related disorder)

Rots et al. (2024).
Pathogenic variants in KMT2C result in a neurodevelopmental disorder distinct from Kleefstra and Kabuki syndromes.American Journal of Human Genetics.
Read the paper

Summary for families:
This study looked at people with changes in the KMT2C gene, sometimes called “Kleefstra Syndrome Type 2.” The researchers found it is actually a different condition, not true KS, and more closely linked to Kabuki Syndrome. This helps doctors diagnose children more accurately.

 

At KSUK, we’ll keep sharing updates in ‘plain English’ while linking you to the original studies where we can. Knowledge empowers both families and doctors.