A mutation in a one-year-old girl: a case report

Case presentation: A one year and two months old girl, born at term with a birth weight of 2990 g with unremarkable prenatal history and non-consanguineous parents, presented with ocular deviation at four months of age. A retinography and brain MRI were performed, showing no abnormalities. At five months of age, she stopped making eye contact, and experienced delayed psychomotor development with sudden social, behavioral and language deterioration. At one year old, she presented dyskinesia affecting hands and feet and ataxia of head and trunk. A whole exome sequencing was requested, which identified a likely pathogenic variant in heterozygosis in KIF1A (c.920G>A, p.Arg307Gin) on chromosome 2q37.3, compatible with NESCAV syndrome, and pathogenic variants on IQCB1 and POLG as secondary findings. Our patient is currently on physical and occupational therapy, and we will continue to follow up on the patient's condition and its clinical course.

Discussion: KIF1A stands for kinesin family member 1A, which is a molecular motor for membrane-bound cargo almost exclusively expressed in the brain and spinal cord. The improper functioning of KIF1A due to genetic variants may result in problems with synaptic plasticity and transmission, learning and memory, leading to the following disorders: (a) neuropathy, hereditary sensory, type IIC; (b) spastic paraplegia 30, autosomal recessive; (c) spastic paraplegia 30, autosomal dominant; and (d) neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impairment (NESCAV syndrome). The NESCAV syndrome may include moderate to severe intellectual disability, language and motor delay, hypotonia, spastic paraparesis, hyperreflexia, postnatal microcephaly, and peripheral neuropathy, and patients may show varying degrees of brain and optic nerve atrophy on MRI.

Final comments: This case further supports the association between KIF1A and NESCAV syndrome, highlighting the importance of genetic testing and screening for KIF1A variants in patients with early-onset ataxia and dyskinesia. By establishing a correct diagnosis, we thereby detect symptoms at an early stage in their evolution where treatment is facilitated, improving our patient's prognosis.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
18 September 2023