Infantile Neuroaxonal Dystrophy 1 and Other PLA2G6-related disorders (PLA2G6)

Pathogenic variants in the gene PLA2G6 cause infantile neuroaxonal dystrophy 1 (INAD) and other PLA2G6-related disorders, which are inherited in an autosomal recessive manner. Infantile neuroaxonal dystrophy 1, also known as neurodegeneration with brain iron accumulation 2A, usually begins during early childhood (before 3 years of age) with psychomotor regression or delay, hypotonia, and progressive spastic tetraparesis. Strabismus, nystagmus, and optic atrophy are common. Disease progression is rapid, resulting in severe spasticity, progressive cognitive decline, and visual impairment. Many affected children do not survive beyond their first decade. A less severe form of INAD is neurodegeneration with brain iron accumulation 2B. This disease has more phenotypic variability and onset typically occurs in early childhood. Compared to patients with INAD, patients with this condition present a slower progression and longer survival times. Less frequently, early adult-onset Parkinson disease with rapid neurodegeneration is caused by PLA2G6. Individuals with two null alleles of PLA2G6 have INAD, whereas atypical NAD phenotype is usually caused by missense variants.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):