NESCAV syndrome (Neurodegeneration and spasticity with or without cerebellar atrophy or cortical visual impair-ment) is an autosomal dominant neurodegenerative disorder char-acterized by developmental delay, progressive spasticity and behav-ioural abnormalities. Additional features may include cortical visual impairment, often associated with optic atrophy, axonal peripheral neuropathy, seizures, dysautonomia, ataxia, and dystonia.
In this article a girl of age three years and two months is reported, referred for genetic analysis based on clinical phe-notype involving bilateral optic nerve atrophy in both eyes and de-velopmental delay. For the purpose of the study, DNA is isolated from a blood sample. Whole-genome sequencing (WGS) and tar-geted bioinformatic analysis of 3313 genes associated with ocular and neurological disorders were performed. Additionally, the patient is screened for genome-wide predicted loss-of-function (pLoF) variants.
One pathogenic heterozygous variant in the KIF1Agene is identified (NM_001244008.2:c.760C>T, p.Arg254Trp, rs879253888), associated with NESCAV syndrome, which is relevant to the patient’s primary indication for testing.
Phenotypic manifestation of NESCAV syndrome occurs in the presence of one pathogenic variant in the KIF1A gene in heterozygous state, regardless of the individual’s sex. The patient’s clinical phenotype and the fact that both parents are unaffected by the disorder suggest that the pathogenic variant has occurred de novo. Clarification of the patient’s genetic diagnosis enables for precise medical genetic counseling of the family and allows for ap-propriate decision-making on disease management. Read the full article here.