Essential tremor in a Charcot-Marie-Tooth type 2C kindred does not segregate with the TRPV4 R269H Mutation

Background: We investigated 4 members of a family with type 2C Charcot-Marie-Tooth (CMT) and self-reported essential tremor (ET). A heterozygous missense mutation, R269H, in the TRPV4 gene was previously reported in this family. Our genotypic data provided a rare opportunity to determine the etiology of the tremor. Methods: Family study; the 4 tremor cases underwent a detailed neurological assessment. Results: The clinical diagnosis of ET was confirmed in all 4 tremor cases based on stringent published research criteria. Two of these also had CMT. We genotyped all 4 family members for the TRPV4 R269H mutation. We confirmed the presence of the TRPV4 R269H mutation in the 2 family members with ET and CMT; however, the TRPV4 R269H mutation did not segregate with ET in the same family. Conclusions: In this particular CMT family, the tremor was clinically attributed to ET. Furthermore, genotype data indicated that the tremor was unlikely to be caused by incomplete penetrance or variable expressivity of the TRPV4 R269H mutation. Hence, the tremor likely represents ET. This establishes that in some CMT families the tremor diathesis likely represents a second disorder, namely ET.