Why did this happen? Inform Network Support The KIF1A gene gives an important instruction for the health of brain cells and nerve fibres. The KIF1A gene gives an instruction for production of the KIF1A protein. This protein helps to control the transport of nutrients and other molecules within nerve cells Rare Chromosome Disorder Support Group, The Stables, Station Road West, Oxted, Surrey RH8 9EE, UK and along nerve fibres. Tel/Fax: +44(0)1883 723356 We all have two copies of the KIF1A gene (one inher- [email protected] I www.rarechromo.org ited from our mother and one inherited from our http://www.kif1a.org/ - a patient-led foundation started by father). Certain changes to the code of the KIF1A parents dedicated to finding a cure for children living gene mean that the KIF1A protein becomes sticky with KIF1A Associated Neurological Disorder (KAND), a rare and binds to the protein produced by the “normal” genetic disease. KIF1A gene. Such changes to the KIF1A protein can This leaflet was made possible by a contribution from be inherited from a parent or happen for the first the Sir Halley Stewart Trust time in the person with the KIF1A neurological condi- tion. Given the nature of KIF1A neurological syn- drome the vast majority of KIF1A gene variants have arisen for the first time (de novo (dn)) in the patient KIF1A syndrome with the condition, rather than being inherited. Can it happen again? rarechromo.org

If the KIF1A variant is not found in blood tests of the parents then the chance of another child being af- fected by the same condition is very low. It is not zero because of something called “gonadal mosaic- ism”. This means that a parent might carry the KIF1A variant in their sperm or eggs, which would not be detected by a blood test. This would mean that This guide is not a substitute for personal medical advice. Families should consult a medically qualified clinician in all matters relating there was a chance of having another affected child. to genetic diagnosis, management and health. Information on Precise advice on this issue should be sought from genetic changes is a very fast-moving field and while the your local Clinical Genetics department. Please note information in this guide is believed to be the best available at the there is a condition caused by changes in both the time of publication, some facts may later change. Unique does its best to keep abreast of changing information and to review its KIF1A gene inherited from mum and the KIF1A gene published guides as needed. This guide was written by Dr. Alisdair inherited from dad, which causes similar symptoms McNeill (Honorary Consultant Clinical Geneticist) and University of to the condition described in this leaflet but which Sheffield, UK. has a higher chance of affecting other children that 2018 Version 1 (CA) Copyright © Unique 2018 the couple have. Rare Chromosome Disorder Support Group Charity Number 1110661 Registered in England and Wales Company Number 5460413 What is KIF1A Syndrome? Most common features: Development KIF1A syndrome is a neurological Spastic paraplegia (stiff, weak legs) sometimes  Growth condition caused by changes in the with ataxia (unsteadiness of movements or tremor) Head circumference is below the average range. KIF1A gene. The condition usually Those with spastic paraplegia also have  Developmental delay in children begins to show symptoms in childhood short intellectual disability, speech/language delay and Babies and children are typically delayed in reaching or early teenage years. (p) developmental delay their developmental “milestones” including rolling, arm One of the main features of the Other possible features include: sitting, moving and walking. condition is weakness and stiffness in Epileptic seizures  Sitting, moving and walking the legs. This is called spastic Thinning of the optic nerve Some people with KIF1A neurological syndrome paraparesis or spastic paraplegia never walk independently, others require walking Leg contracture (spastic means stiff, “para” means legs aids or have very limited walking ability. In a few Pressure sores and “paresis/plegia” means weak). people with KIF1A neurological syndrome walking is People with the condition also often Spinal curvature e.g. scoliosis or kyphosis relatively normal. have shaking (tremor) of their hands Autism Spectrum Disorders (ASD)  Speech called ataxia. Most people with KIF1A neurological syndrome have Most people with KIF1A neurological  Epilepsy been reported to have delay to speech and syndrome also have developmental long A minority of people with KIF1A neurological syn- language, with variable severity. delay (slowness in achieving (q) drome develop epilepsy. Several cases of epileptic arm  Learning developmental milestones). This fits have been reported in the medical literature, in- condition affects the nervous system cluding: a boy who started to experience generalised Most people with this condition will need to attend a (brain, spinal cord and peripheral tonic-clonic seizures at 15 years (Hotchkiss 2016); a special school or require additional support. nerves) but no other parts of the body. 16-year-old boy diagnosed with generalized tonic-  Behaviour Some affected children first come to clonic seizures; a 6-year-old boy with refractory myo- No clear association with autism or other medical attention with developmental clonic, tonic and generalized tonic-clonic seizures behavioural problems has been reported. A single KIF1A (Nieh 2015); four cases with unspecified seizures person with a KIF1A variant and autism/ADHD has delay but then show signs of spastic gene paraplegia. (Lee 2015; Kun Cheon 2017). been reported but it is not clear if this is due to the Chromosome 2  Thinning of the optic nerve KIF1A variant or is a coincidence (Tomaselli 2017). Some people with KIF1A variants have thinning of Management: the nerve at the back of the eye (optic nerve hy- Medical concerns  Follow up by a Neurologist for management of poplasia), which transmits visual signals to the brain.  Spastic parapelgia spasticity or other neurological features. This can cause problems with vision. Progressive weakness and stiffness of the legs  EEG (measurement of the brain’s electrical leads to poor mobility. This may mean that  Spinal curvature activity) if seizures are suspected. individuals walk with an awkward gait or may need A few children and adults have been affected by sco-  Follow up by a Paediatrician consultant to a walking aid or wheel chair in more severe cases. liosis (a sideways curve of the spine) or kyphosis (an monitor growth and development.  Leg contracture and pressure sores outward curve resulting in a hump). The curvature  Physiotherapy may help with leg stiffness. can be treated with physiotherapy and exercises. A  Speech and language therapy as needed. There is a possibility of leg contractures (the support brace may be needed or in severe cases spi-  Assessment of vision and hearing. muscles or joints become shortened over time) nal fusion surgery may be necessary to straighten  Genetic counselling as needed to provide and/or pressure sores (injuries to the skin and the spine using rods. support and advice about the genetic condition. underlying tissue as a result of sustained pressure) due to poor mobility.