Neurodegeneration with brain iron accumulation syndromes (NBIAS) [14 genes]

NBIAS stands for ‘neurodegeneration with brain iron accumulation syndromes’ and covers a series of heterogeneous, often overlapping entities whose main characteristic is the accumulation of iron in the brain. This accumulation is predominantly observed at the level of the basal ganglia (mainly in the globus pallidus, substantia nigra, and adjacent areas) on brain MRI (T2, spin-echo, and gradient echo sequences). One of its most frequent forms is pantothenate kinase-associated neurodegeneration (PKAN, formerly known as Hallervorden-Spatz syndrome), which is generally recognized on MRI by the ‘eye of the tiger’ sign (a hypointense area with a hyperintense center in the globus pallidus).

The prevalence of these syndromes is estimated at around 1-3 every 1,000,000 individuals. They present clinically as neurodegenerative diseases with movement disorders and pyramidal, cerebellar, autonomic, and eventually cognitive and psychiatric signs.

Several causative genes have been identified for NBIAS. These genes are included in our panel, whose diagnostic yield allows explaining approximately 65% of cases (Schneider et al., 2016). In order of importance, it is worth highlighting the following genes: PANK2 (35-50%), PLA2G6 (20%), C19orf12 (6-10%), and WDR45 (1-2%) (Gregory and Hayflick, 2014).