Neocortical and hippocampal volume loss in a human ciliopathy: A quantitative MRI study in Bardet-Biedl syndrome

Cilia are ubiquitous cell surface organelles with diverse roles from embryogenesis to adult life. The neurodevelopmental functions of the cilium are currently under investigation in animal systems, but relevance to human brain development remains uncertain. We present the first systematic investigation of structural neuroanatomy in a ciliopathy-Bardet-Biedl syndrome (BBS). Qualitative and quantitative aspects of brain structure were evaluated via magnetic resonance imaging in 10 patients with BBS (ages 14-28 years). In comparison to age and gender-matched healthy controls, BBS patients had significantly reduced total gray matter (GM) volume but no total white matter (WM) or cerebrospinal fluid volume changes. Voxel-based morphometric analysis indicated regional GM volume loss bilaterally in the anterior temporal lobes and in the medial orbitofrontal cortex, and WM volume loss in the right inferior longitudinal fasciculus. Region-of-interest measurements revealed reduced volume of the hippocampus. Two patients were found to have ventriculomegaly. Global GM reduction and regional volume reductions in the temporal lobe may underlie the learning disabilities and behavioral problems experienced by some patients with BBS. These findings are consistent with previous observations in mouse models of BBS, and further implicate the cilium in neurodevelopmental processes relevant to human cognitive function.