KIF1A-associated neurological disorder: Year of the Zebra

KIF1A-associated neurological disorder, or KAND for short, is a group of rare genetic conditions that result in progressive neurological dysfunction due to alterations in the KIF1A gene. The KIF1A gene codes for a specialized protein called kinesin found in neurons. Kinesin helps transport nutrients and other important molecules along the neuron’s axon, like a minecart on a railway track.

Alterations affecting the KIF1A gene lead to faulty kinesin that either stops or slows down axonal transport, resulting in neuronal dysfunction and even cell death.

So far, researchers have identified over 100 alterations affecting the KIF1A gene. These alterations can be inherited in autosomal dominant or recessive patterns, however, the most common and most severe forms are caused by de novo alterations, meaning they arise spontaneously and are not inherited.

Now, KAND is a spectrum-type condition, meaning the symptoms and progression vary greatly from one individual to another depending on the underlying gene alteration and pattern of inheritance.

One of the main features is spastic paraplegia, a condition where muscle weakness and stiffness in the legs causes the individual’s movements to jerk, affecting their ability to walk and move around.

Some children may also have a delay in reaching childhood milestones, like walking and talking, and they may experience difficulty with coordination and balance; as well as seizures and visual disturbances. Additionally, because brain development can be affected, individuals may have microcephaly, which is when head size is smaller than expected for an individual’s age.

Certain alterations in the KIF1A gene cause damage to sensory nerves, resulting in numbness and a tingling or burning sensation in the hands or feet. Less frequently, individuals may have dysfunction of the autonomic nerves that control involuntary bodily functions, like body temperature. As a result, individuals with KAND may have unexplained episodes of fever, which may be mistaken for having an infection.