Multi-organ investigation in 16 CADASIL families from central Italy sharing the same R1006C mutation

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) may involve many target organs with relevant variability among affected individuals. We performed a multi-organ assessment tapping nervous system, skeletal muscle and cardiovascular system in thirty-nine individuals belonging to 16 families from Central Italy sharing the same R1006C CADASIL mutation. Stroke prevalence was larger in female patients (66.7%) than in males (23.8%); high levels of CKemia were quite frequent (21.6%) and were related to a myopathy without mitochondrial alterations; several individuals had atrial septal aneurysm (10.3%). No specific relationships between common cardiovascular risk factors and clinical manifestations were found. The present systematic study thus identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. This kind of comprehensive approach is necessary to define clinical course, prognosis and treatment options for a multi-organ disease such as CADASIL.

► CADASIL involves many target organs with high variability among individuals. ► R1006C CADASIL mutation is very frequent in central Italy. ► We made a multi-organ assessment in 39 subjects sharing the R1006C CADASIL mutation. ► The study identified several gender-related, myopathic and cardiovascular peculiarities of R1006C mutation. ► Systematic clinical studies on single mutations are necessary to comprehend variability of CADASIL.