Congenital Mirror Movements in a New Italian Family

Abstract

Mirror movements (MMs) occur on the contralateral side of a limb being used intentionally. Because few families with congenital MMs and no other neurological signs have been reported, the underlying mechanisms of MMs are still not entirely clear. We report on the clinical, genetic, neurophysiological and neuroimaging findings of 10 of 26 living members of a novel four-generation family with congenital MMs. DCC and RAD51 were sequenced in affected members of the family. Five of the ten subjects with MMs underwent neurophysiological and neuroimaging evaluations. The neurophysiological evaluation consisted of electromyographic (EMG) mirror recordings, investigations of corticospinal excitability, and analysis of interhemispheric inhibition using transcranial magnetic stimulation techniques. The neuroimaging evaluation included functional MRI during finger movements. Eight (all females) of the ten members examined presented MMs of varying degrees at the clinical assessment. Transmission of MMs appears to have occurred according to an autosomal-dominant fashion with variable expression. No mutation in DCC or RAD51 was identified. EMG mirror activity was higher in MM subjects than in healthy controls. Short-latency interhemispheric inhibition was reduced in MM subjects. Ipsilateral motor-evoked potentials were detectable in the most severe case. The neuroimaging evaluation did not disclose any significant abnormalities in MM subjects. The variability of the clinical features of this family, and the lack of known genetic abnormalities, suggests that MMs are heterogeneous disorders. The pathophysiological mechanisms of MMs include abnormalities of transcallosal inhibition and corticospinal decussation.

Keywords: corticospinal excitability; electromyography; functional magnetic resonance imaging; interhemispheric inhibition; mirror movements; neurophysiology; transcranial magnetic stimulation.

Figure 1

The four‐generation family tree of the MM subjects enrolled in the present study (see Table 1 for further details). *DCC and RAD51 sequenced in these individuals.

Figure 2

EMG traces from the FDI‐TASK and the FDI‐MIRROR during the motor task and single‐pulse TMS of M1 contralateral to the hand performing the motor task in 2 representative subjects with a marked (A, subject III‐3) and a mild phenotype (B, subject III‐11). Upper traces show the DC‐corrected and rectified EMG from the FDI‐TASK and the FDI‐MIRROR representing 15 movements. Lower traces show the MEP responses in the FDI‐TASK and FDI‐MIRROR. Note that an ipsilateral MEP was only detected in the subject exhibiting the highest EMG mirroring activity.

Figure 3

Measurements of s‐IHI were higher in the familial member group than in the healthy controls (*P = 0.022), whereas l‐IHI did not differ between the two groups.

Figure 4

fMRI assessment during active finger tapping of the dominant hand consistently revealed an activation of contralateral frontal and parietal areas with no differences with respect to occurrence and severity of MMs.