FAQs

KDM5C-related disorder, referred to as Claes-Jensen syndrome, is caused by a variant in the KDM5C gene. The full role of KDM5C in the body is not fully understood yet, but it is known that KDM5C plays an important role in cells of the nervous system, such as neurons. Neurons not only help the different parts of our brains communicate with each other, they help our brain communicate with the rest of our body including muscles, eyes and digestive tract. Variants in KDM5C can reduce or diminish the function of the protein produced by KDM5C, affecting the way cells such as neurons work. When neurons aren’t working properly, people can experience symptoms that affect many aspects of their health and daily functioning.

KDM5C-related disorder has also been referred to as Claes-Jensen syndrome. Claes-Jensen syndrome was named after the geneticists that first described the condition in the early 2000’s, Dr. Stephan Claes and Dr. Lars Jensen. Based on their research and experience with people with this condition, it was named Claes-Jensen syndrome. 

As more people are being identified to have KDM5C variants, our understanding of the condition has evolved from the original description of Claes-Jensen syndrome. While the original condition was described to have a more specific presentation, we now know that the condition represents a spectrum of presentations and clinical features. To make sure that everyone who is affected, regardless of their biological sex or their clinical features, is represented by the same terminology, the terms KDM5C-related neurodevelopmental disorder, KDM5C-related disorder, or simply KDM5C, are commonly used. This terminology is more inclusive of people who have received diagnoses of Claes-Jensen, as well as people who may have variants in KDM5C but do not fit the clinical description of Claes-Jensen.

You may also read some research that refers to KDM5C as JARID1C or SCMX. These are different names for the same gene. Again, as our understanding of genetics and the role of this gene in the human body has evolved, KDM5C was felt to be a more appropriate name for the gene.

People with KDM5C variants can experience a range of different features, including, but not limited to:

• Global developmental delay

  • People with KDM5C-related disorder are often delayed in several areas of development, including:

    • Gross motor skills, like crawling and walking

    • Fine motor skills, like using utensils or crayons

    • Speech and language

      • Some people with KDM5C-related disorder have limited or absent speech, but often use alternate ways of communicating, like sign language or assistive communication devices

• Intellectual disability or cognitive differences

  • People with KDM5C variants can have a harder time with learning or functioning independently

• Different muscle tone

  • People can have hypotonia (low muscle tone), hypertonia (increased muscle tone), or a combination of both in different parts of the body

• Behavioral differences

  • Impulsivity

  • A short attention span

  • Aggressive behavior

  • Emotional dysregulation

  • Autism, or autistic-like behavior

  • Anxiety

  • Hyperactivity

  • Attention deficit hyperactivity disorder (ADHD)

  • Repetitive stereotypic behaviors (hand flapping, body rocking, head banging, spinning)

• Seizures

• Growth differences

  • Short stature is most common, though some people have been reported to be overweight or have general overgrowth

• Vision issues

  • Different eye movements, like strabismus

  • Farsightedness

• Gastrointestinal issues

  • Constipation is common in people with KDM5C-related disorder and can be significant

  • Feeding difficulties

• Sleep issues

• Different physical features

  • Small forehead

  • Small chin

  • Lower facial muscle tone

  • Flat philtrum

  • Thin upper lip

  • High or narrow palate

  • Deep set eyes

  • Short fingers

  • Small feet

  • Excess body hair

KDM5C-related disorder is a spectrum. Not each person with a KDM5C variant will develop all of these features. It is not possible to predict how each person with KDM5C-related disorder will grow and develop; even people in the same family with the same variant can be different. Each person with KDM5C will have their own experience with the condition. Additionally, we do not yet know all of the health effects caused by KDM5C and some people might have features that are not associated with KDM5C yet.

It is important to note that males with a pathogenic variant in KDM5C are expected to have many of the above features. Females usually have more mild cognitive differences and can range from having moderate developmental delay to being virtually unaffected and not knowing that they have a KDM5C variant. Females can also experience some of the above features, regardless of their cognitive function.

Currently, there is no cure or specific treatment for KDM5C-related disorder. Each person’s care is based on their features and is focused on symptom management. Some doctors or specialists that might be on a person’s care team may include:

• Neurology

• Developmental Pediatrics

• Gastroenterology

• Orthopedics

• Endocrinology

• Ophthalmology

• Sleep Medicine

• Physical Medicine and Rehabilitation

• Genetics

• Feeding therapy

• Physical therapy

• Speech therapy

• Occupational therapy

• Behavioral therapy

• Psychology and/or neuropsychology

These specialists can be discussed with the provider who made the diagnosis of KDM5C-related disorder to see if they are appropriate for your loved one. Not every person will need all of these.

The features of KDM5C-related disorder overlap with many other neurodevelopmental disabilities. The only way to know for sure if someone has a KDM5C variant is through genetic testing. This is usually done through a gene panel, whole exome sequencing, or whole genome sequencing.

KDM5C is located on the X chromosome. People who are biologically male have one X chromosome. People who are biologically female have two X chromosomes. When a biological male has a disease-causing variant in the KDM5C gene, it is expected that he will have a combination of the features listed above. When a biological female has a disease-causing variant in the KDM5C gene, if she has features of KDM5C-related disorder, it is generally expected that she will have more mild features and cognitive effects than a male, but she could have significant health challenges. However, some females may not have any features. Like with males, it is not possible to predict what features a female may have.

There are people who have a KDM5C variant as the result of a de novo, or new, variant, and people who have inherited the variant from their mother who may not have features or may not have known she had the variant. De novo means that a person did not inherit that variant from one of their biological parents and it was brand new in them. 

However, the possibility of a phenomenon called germline or gonadal mosaicism cannot be excluded. This means that the variant is only found in that person’s father’s sperm or mother’s eggs, so they do not have KDM5C, but can pass it on to their children. Taking this possibility into account, the chance of two people testing negative for the variant and having another child with KDM5C is around 1%. See this diagram to better understand the KDM5C inheritance pattern.

Females with KDM5C variants may have biological children and can pass this variant to their children. There would be a 50% chance of each of her children, male or female, to inherit the variant (see this diagram). If the variant is passed to a son, he will have KDM5C-related disorder and is expected to have many of the features above. If the variant is passed to a daughter, it is currently not possible to predict how she will be affected.

Most males with KDM5C variants do not have biological children. However, if they do, all of their daughters and none of their sons would inherit the variant.

It is common for genetic conditions, including KDM5C-related disorder, to have intrafamilial variability, meaning that people in the same family with the same variant can present in different ways. It is not possible to predict what features a person with a KDM5C variant may develop.

It is highly recommended that each person who is diagnosed with KDM5C-related disorder meet with a medical geneticist and/or genetic counselor to discuss testing for relatives and to learn more about recurrence risks. People residing in the United States can find a genetic counselor by visiting: https://findageneticcounselor.nsgc.org/.