Primary familial brain calcification (PFBC), widely known as Fahr's disease, is 
a rare disorder caused by pathogenic variants in SLC20A2, PDGFB, PDGFRB, XPR1, 
or MYORG genes. It is characterized by ectopic brain calcification, mostly 
affecting basal ganglia, thalamus, and cerebellum. PFBC patients can present a 
wide spectrum of symptoms including cognitive, neuropsychiatric, and motor 
alterations. However, it is well established that PFBC individuals also present 
high clinical heterogeneity, though the genetic cause of this phenotypic is not 
understood. Recently, Wang et al. (Front Cell Neurosci. 
https://doi.org/10.3389/fncel.2019.00250, 2019) reported on the role of MEA6 
gene in cerebellar development and motor performance, also citing that MEA6 
might be linked to PFBC. A MEA6 variant was described in 2007 as a PFBC 
candidate gene in an American family. However, this family was later linked to 
the SLC20A2 gene discarding the MEA6 as a PFBC-gene and also some members were 
confirmed as phenocopy. Additionally, five independent studies have been shown 
that variants in a second gene, not related to PFBC, were identified in PFBC 
patients, promoting a complex and heterogeneous phenotype. Thus, further 
investigation is required to explain whether and how MEA6 contributes to the 
clinical presentation in this American family. Finally, this letter highlights 
the possible digenic influence on clinical heterogeneity of PFBC patients, and 
such a possibility might advance our understanding of PFBC phenotypes.