ORPHA: 238722;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q15.1 | Mirror movements 2 | 614508 | Autosomal dominant | 3 | RAD51 | 179617 |
A number sign (#) is used with this entry because of evidence that mirror movements-2 (MRMV2) is caused by heterozygous mutation in the RAD51 gene (179617) on chromosome 15q15.
Mirror movements are involuntary movements of a side of the body that mirror intentional movements on the opposite side. Mild mirror movements are physiologic in young children and gradually disappear within the first decade of life, likely due to maturation of the motor network. Mirror movements that persist beyond age 10 years represent a rare disorder usually showing autosomal dominant inheritance with incomplete penetrance (summary by Depienne et al., 2012).
For a discussion of genetic heterogeneity of mirror movements, see MRMV1 (157600).
Depienne et al. (2011) and Depienne et al. (2012) reported a large 4-generation French family in which 8 individuals had congenital mirror movements. Affected individuals had involuntary mirror movements affecting the hands and forearms, resulting in functional disability in fine manual activities, and in pain and cramping during sustained manual activities, including writing. The disorder showed a stable course, and none required treatment. There were no associated disorders. An unrelated German family with 2 affected individuals had a similar phenotype.
Franz et al. (2015) reported a family (family A) in which at least 11 individuals spanning 3 generations had mirror movements. Eight patients had visually confirmed mirror movements, 2 were reportedly affected according to family history, and 1 patient (patient IV.6, aged 30) did not have visually apparent mirroring, but did show subtle mirror movements detected by an accelerometer glove. In this family, those with visually apparent mirror movements had 'actual' mirroring, in which the non-volitional hand and fingers virtually mirrored the volitional hand precisely in all movements.
Trouillard et al. (2016) reported a multigenerational family from Norway in which 8 individuals had congenital mirror movements. Four mutation carriers had obvious mirror movements in the hands that disturbed activities of daily living, whereas the other 4 mutation carriers had no complaints despite mild mirror movements, indicating intrafamilial variability.
The transmission pattern of MRMV2 in the families reported by Depienne et al. (2012) was consistent with autosomal dominant inheritance with incomplete penetrance (50% in 1 family).
By exome sequencing of a large French family with mirror movements reported by Depienne et al. (2011), Depienne et al. (2012) identified a heterozygous truncating mutation in the RAD51 gene (R254X; 179617.0003). The mutation was found in 8 affected individuals and in 8 unaffected individuals, indicating incomplete penetrance. A second truncating mutation in the RAD51 gene (179617.0004) was identified in a German family with the disorder. The authors concluded that haploinsufficiency was the pathogenic mechanism. Rad1 expression was found in the developing mouse cortex, and specifically in a subpopulation of corticospinal axons at the pyramidal decussation. The mechanism linking RAD1 deficiency to the disorder was unclear: insufficient RAD51-related DNA repair during early corticogenesis might lead to excessive apoptosis and altered central nervous system development; however, RAD51 may have a direct or indirect role in axonal guidance.
Trouillard et al. (2016) identified a heterozygous R254X mutation in the RAD51 gene in 8 members of a Norwegian family with MRMV2. The mutation, which was found by direct sequencing of the RAD51 gene, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed.
In 2 unrelated patients with sporadic MRMV2 (female probands from families 3 and 16), Meneret et al. (2014) identified heterozygous missense variants in the RAD51 gene (H47R and I137F) by direct Sanger sequencing. Both variants were inherited from the patients' unaffected mothers, and 1 of them (H47R) was also present in an unaffected brother. Functional studies and studies of patient cells were not performed. The patients were ascertained from a cohort of 6 familial and 20 simplex cases of congenital mirror movements who were specifically screened for mutations in the DCC (120470) and RAD51 genes.
In 9 individuals spanning 2 generations of a family (family A) with MRMV2, Franz et al. (2015) identified a heterozygous missense mutation in the RAD51 gene (R250Q; 179617.0006). The variant, which was found by a combination of linkage analysis and exome sequencing, segregated with the disorder in the family. Functional studies of the RAD51 variant and studies of patient cells were not performed. One variant carrier (patient IV.6) did not have overt mirror movements, but did show subtle mirror movements detected by an accelerometer glove.
Depienne, C., Bouteiller, D., Meneret, A., Billot, S., Groppa, S., Klebe, S., Charbonnier-Beaupel, F., Corvol, J.-C., Saraiva, J.-P., Brueggemann, N., Bhatia, K., Cincotta, M., and 13 others. RAD51 haploinsufficiency causes congenital mirror movements in humans. Am. J. Hum. Genet. 90: 301-307, 2012. [PubMed: 22305526] [Full Text: https://doi.org/10.1016/j.ajhg.2011.12.002]
Depienne, C., Cincotta, M., Billot, S., Bouteiller, D., Groppa, S., Brochard, V., Flamand, C., Hubsch, C., Meunier, S., Giovannelli, F., Klebe, S., Corvol, J. C., Vidailhet, M., Brice, A., Roze, E. A novel DCC mutation and genetic heterogeneity in congenital mirror movements. Neurology 76: 260-264, 2011. [PubMed: 21242494] [Full Text: https://doi.org/10.1212/WNL.0b013e318207b1e0]
Franz, E. A., Chiaroni-Clarke, R., Woodrow, S., Glendining, K. A., Jasoni, C. L., Robertson, S. P., Gardner, R. J. M., Markie, D. Congenital mirror movements: phenotypes associated with DCC and RAD51 mutations. J. Neurol. Sci. 351: 140-145, 2015. [PubMed: 25813273] [Full Text: https://doi.org/10.1016/j.jns.2015.03.006]
Meneret, A., Depienne, C., Riant, F., Trouillard, O., Bouteiller, D., Cincotta, M., Bitoun, P., Wickert, J., Lagroua, I., Westenberger, A., Borgheresi, A., Doummar, D., and 18 others. Congenital mirror movements: mutational analysis of RAD51 and DCC in 26 cases. Neurology 82: 1999-2002, 2014. [PubMed: 24808016] [Full Text: https://doi.org/10.1212/WNL.0000000000000477]
Trouillard, O., Koht, J., Gerstner, T., Moland, S., Depienne, C., Dusart, I., Meneret, A., Ruiz, M., Dubacq, C., Roze, E. Congenital mirror movements due to RAD51: cosegregation with a nonsense mutation in a Norwegian pedigree and review of the literature. Tremor Other Hyperkinet. Mov. (N.Y.) 6: 424, 2016. Note: Electronic Article. [PubMed: 27830107] [Full Text: https://doi.org/10.7916/D8BK1CNF]