Marked differences in clinical phenotype may exist within the same family in mitochondrial membrane protein-associated neurodegeneration (MPAN), a form of the rare, inherited disorder neurodegeneration with brain iron accumulation (NBIA).
Why this matters
To date, 10 different genes have been associated with NBIA, potentially explaining the significant clinical heterogeneity observed between different types of NBIA.
MPAN, also known as NBIA-4, is a form of NBIA caused by mutations in the C19Orf12 gene; typically, most cases of MPAN have a similar clinical presentation and course, and similar neuropathological features.
However, the investigators identified a Hungarian family wherein an autosomal dominant inheritance of MPAN was associated with significant intrafamily heterogeneity.