KANSL1-Related Syndrome

KANSL1-related syndrome happens when there are changes in the KANSL1 gene. These changes can keep the gene from working as it should.  

Some people have a change that affects only the KANSL1 gene. Other people are missing a larger piece of DNA that includes the KANSL1 gene.  

KANSL1-related syndrome is also called 17q21 deletion syndrome because the KANSL1 gene is found on chromosome 17, one of the body’s 46 chromosomes. Both syndromes share the same set of symptoms. These syndromes are also known as Koolen-de Vries syndrome.

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 KANSL1-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 KANSL1-related syndrome, the sibling’s risk of having a child who has KANSL1-related syndrome depends on the sibling’s genes and their parents’ genes.

• If neither parent has the same genetic variant causing KANSL1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit KANSL1-related syndrome.

As of 2024, over 156 people with KANSL1-related syndrome have been identified in a medical clinic. This includes people with pathogenic or likely pathogenic variants in KANSL1 and people with large deletions that include KANSL1. 

People who have KANSL1-related syndrome may look different. Appearance can vary and can include some but not all of these features: 

• Long face 
• Pear-shaped nose with a round tip 
• Large ears 
• An opening between the eyelids that is narrow or has an upward slant 
• Drooping eyelids 
• A skin fold covering the inner corner of the eye

Scientists and doctors have only just begun to study KANSL1-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 KANSL1-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.

Speech and Learning  

Most people with KANSL1-related syndrome had developmental delay and/or intellectual disability, and speech delay. People usually had mild to moderate intellectual disability. Speech issues included oral muscle weakness and apraxia in early childhood. First words were spoken between 2 and a half to 3 and a half years old. 

• 129 out of 131 people had developmental delay or intellectual disability (99 percent) 
• 109 out of 111 people had speech delay (98 percent) 

Behavior 

People with KANSL1-related syndrome had behavioral issues, including friendly behavior, features of autism, attention-deficit/hyperactivity disorder (ADHD), or anxiety. 

• 103 out of 115 people had friendly behavior (90 percent) 

Brain 

One-half of people with KANSL1-related syndrome had seizures and/or brain changes observed on magnetic resonance imaging (MRI). Common seizure types included generalized seizures, unilateral clonic seizures, and focal seizures. Brain changes included ventriculomegaly, aplasia/hypoplasia of the corpus callosum, hydrocephalus, Arnold-Chiari malformation, and intraventricular hemorrhage. Most people had low muscle tone (hypotonia). 

• 69 out of 135 people had seizures (51 percent) 
• 60 out of 118 people had brain changes on (51 percent) 
• 122 out of 134 people had hypotonia (91 percent)

Growth 

Some people with KANSL1-related syndrome had short height, and they had either intrauterine growth restriction (IUGR) or low birth weight. Some people had a smaller than average head size (microcephaly) or a larger than average head size (macrocephaly).  

• 34 out of 104 people had short height (33 percent) 
• 38 out of 121 people had IUGR or low birth weight (31 percent) 
• 8 out of 102 people had microcephaly (7 percent) 
• 15 out of 83 people had macrocephaly (18 percent)

Vision and Hearing 

 The most common eye issues were ptosis (droopy eyelids), strabismus (crossed eyes), and refractive errors (when the shape of the eye causes a blurred image). Some people had hearing impairments. 

• 68 out of 114 people had eye issues (60 percent) 
• 22 out of 101 people had hearing impairment (22 percent) 

Muscle and skeletal issues 

People with KANSL1-related syndrome often had musculoskeletal findings, including hypermobile joints, scoliosis/kyphosis (curvature of the spine), or changes in the pectus (breast bone). 

• 99 out of 127 people had musculoskeletal findings (78 percent) 
• 63 out of 99 people had hypermobile joints (64 percent) 
• 40 out of 127 people had scoliosis/kyphosis (32 percent) 
• 15 out of 85 people had changes in the pectus (18 percent)

Other medical findings 

Some people had heart defects, such as a hole in the heart (atrial septal defect or ventricular septal defect), disease of the heart muscle (cardiomyopathy), or a dilation of the upper part of heart (aortic root dilation). 

One-half of people with KANSL1-related syndrome had genitourinary defects, including cryptorchidism (undescended testicles), hypospadias (when the opening is not at the end of the penis), hydronephrosis/vesicoureteral reflux (when urine has difficulty flowing out the kidney), or kidney duplication. 

Some people had hormone issues, including growth hormone issues or precocious puberty. Some people had skin findings. 

• 47 out of 132 people had heart defects (36 percent)
• 62 out of 127 people had genitourinary defects (49 percent)

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.”

• Learn more about Simons Searchlight – www.simonssearchlight.org/frequently-asked-questions
• Simons Searchlight webpage with more information on KANSL1 – www.simonssearchlight.org/research/what-we-study/kansl1
• Simons Searchlight KANSL1 Facebook community – https://www.facebook.com/groups/kansl1