Author: Wendy Kay Chung, MD, Columbia University Medical Center 

Reviewed: February 2022 

SUMMARY

KIF1A associated neurological disorder (KAND) is caused by one or more disease-causing variations in the KIF1A gene. KIF1A is responsible for producing the KIF1A protein. This protein is, in turn, vital for the health of brain cells and nerve fibers.  

Even different variations in the gene can lead to similar signs and symptoms. However, different individuals will experience KAND differently. KAND varies in terms of: 

• The specific symptoms that develop 
• The progression of the symptoms 
• The overall severity of the disorder 

KAND is best described as a spectrum-type disorder. It ranges from causing mild symptoms to severe, life-threatening complications. This difference is in part dependent on: 

• Where in the gene the variation occurs 
• The type of variation that occurs 
• How the gene is inherited 

In some people, KIF1A variants are inherited from both parents. In others, it can be inherited from only one parent. KIF1A variants can also occur spontaneously. This means that it can be a new change to a child’s gene instead of an inherited one. KAND is managed based on each child’s symptoms. 

Disorder Overview

DESCRIPTION

Signs and symptoms of KAND are progressive. They can also vary greatly from one individual to another. These differences depend on: 

• Where in the gene the variation occurs 
• The type of variation that occurs 
• The inheritance pattern 
• Other factors 

Researchers and clinicians are still learning about KAND. A global KIF1A Patient Registry and Natural History Study is now following patients over time to learn more about this gene, variations in the gene, and its impact on health.

KAND is Often Underdiagnosed or Misdiagnosed 

KAND is underdiagnosed. This means that many people who have the disorder do not know it is caused by KAND. The KIF1A.ORG foundation knows of more than 350 families around the world with documented KIF1A variants. While those known to be living with KAND are limited, it is estimated that the KAND likely affects tens of thousands of people.  

Many have also been misdiagnosed with disorders with similar symptoms. In fact, about 1 in 4 of those later diagnosed with KAND previously had a cerebral palsy diagnosis. This is partly because KIF1A gene mutations are difficult to diagnose without extensive genetic testing. Common misdiagnoses include: 

• Cerebral palsy 
• Rett syndrome 
• Charcot-Marie-Tooth disease

SIGNS AND SYMPTOMS

Symptoms of KAND fall into several categories:

CAUSES

KAND is caused by a variation in the KIF1A gene. The variation can be: 

• De novo. This means that the KIF1A change newly occurred in the child’s genetic code. 
• Inherited and one gene affected. This means that a variant KIF1A gene was inherited from one parent and a normal KIF1A gene was inherited from the other parent. There is only one variant KIF1A gene. 
• Inherited and two genes affected. This means that variant KIF1A genes were inherited from both parents. There are two variant KIF1A genes.

LABORATORY INVESTIGATIONS

A diagnosis of KAND may be made based on: 

• Symptoms 
• A detailed patient and family history 
• A thorough clinical evaluation 
• A variety of specialized tests 

Genetic Testing 

A diagnosis can be confirmed with genetic testing. Some people use a genetic panel that tests a subset of genes. However, the best genetic test for identifying KAND is called whole exome sequencing (WES). Sometimes blood from parents is also used as part of WES. It can help with comparison. WES can show: 

• Variations in the KIF1A gene that are known to cause disease 
• Variations in other genes known to cause symptoms like KAND 

Other Testing 

People who are diagnosed with KAND may be given additional tests that can help show the extent of the disease. Some examples include: 

• Routine neurologic exams 
• Neurophysiologic tests 
• Neuroimaging 

Additionally, an eye exam with an ophthalmologist can check for visual impact from the disorder, such as: 

• Optic nerve atrophy 
• Cortical visual impairment 
• Strabismus 
• Cataracts 

KAND is progressive, so changes can develop over time. Children with KAND should be regularly checked by appropriate specialists.

TREATMENT AND THERAPIES

Basic Treatment and Therapies 

KAND is treated based on the symptoms that are present. There are no official care guidelines for those with KAND. Treatment may require a team of specialists working together. Genetic counseling is recommended for people with KAND and their families. Support for the entire family may also be necessary. 

Following an initial diagnosis:

• First, a doctor may assess the child’s development. 
• Second, they will recommend appropriate occupational, physical, speech, and feeding therapies. 
• Third, the child may need ongoing assessments and adjustments over time.  

Additional services might also be needed. These can include:

• Medical services 
• Social services 
• Vocational services 
• Specialized learning programs 

Some specific symptoms that should be addressed include: 

• Seizures. Should be assessed and treated. 
• Vision. Should be assessed and safety measures set in place. 
• Spasticity, or tight muscles. May be treated with a muscle relaxant like baclofen. 

Other Beneficial Therapies 

KAND patients may also benefit from: 

• Hippotherapy (Horseback riding therapy) 
• Aquatic therapy (therapy performed in water) 
• Other evidence-based practices 

OUTLOOK

While there is no treatment or cure for KAND yet, the main goal for treating KAND symptoms is “care until a cure.” Because the symptoms and expected outcomes are different for each person with KAND, the outlook varies a lot from patient to patient.  

Though a person cannot yet be cured of the disorder, many things can help those with KAND function optimally in school, work, and other areas of life. Children with KAND can benefit from: 

• An individualized plan of care 
• An individualized education plan 
• Therapies 
• Medications 
• Orthotics 
• Assistive devices 
• Learning or emotional support services

RELATED DISORDERS

There are many disorders that can cause signs and symptoms similar to those KAND. Some of these disorders are: 

• Other forms of hereditary spastic paraplegia (HSP) 
• Other forms of hereditary sensory and autonomic neuropathy (HSAN) 
• Some forms of Charcot-Marie-Tooth disease
• Rett syndrome 
• Immune-mediated neuropathies 
• Metabolic disorders, like Fabry disease 
• Amyloidosis 
• Motor neuron disorders 
• Leukodystrophies 
• Spinocerebellar ataxias 
• Cerebral palsy 
• Disorders that cause structural differences in the brain or spinal cord 

Research 

Currently, there are no listings for KIF1A Associated Neurological Disorder (KAND) in ClinicalTrials.gov. Check back often and talk with your healthcare provider to identify upcoming trials.   

If you have an interest in searching for any future trials that may be starting:  

1. Go to the Home page of ClinicalTrials.gov  
2. Under “Status”, click on “Recruiting and not yet recruiting studies”  
3. Under “Condition or disease”, type KIF1A Associated Neurological Disorder or KAND in the field. A drop-down list will appear if this disorder is included.  
4. You can narrow the search by entering a Country name  
5. Once on the disorder page of trials, narrow your search under

 ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details.     

 Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits.

Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits.  

The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only. CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options.

Reviews and Guidelines:

Boyle L, Rao L, Kaur S, Fan X, Mebane C, Hamm L, Thornton A, Ahrendsen JT, Anderson MP, Christodoulou J, Gennerich A, Shen Y, Chung WK. Genotype and defects in microtubule-based motility correlate with clinical severity in KIF1A-associated neurological disorder. HGG Adv. 2021 Apr 8;2(2):100026. https://doi.org/10.1016/j.xhgg.2021.100026. Epub 2021 Jan 30. PMID: 33880452; PMCID: PMC8054982. 

National Organization for Rare Disorders, Inc. KIF1A related disorder [Internet]. Danbury, CT.: National Organization for Rare Disorders (NORD). 2019. Available from: https://rarediseases.org/rare-diseases/kif1a-related-disorder/  

KIF1A.ORG. Frequently asked questions [Internet]. New York, NY: KIF1A.ORG. 2021. Available from: https://www.kif1a.org/faq/