Confirmation of congenital mirror movements in a 19-month-old boy by detection of a de novo DCC mutation

Mirror movements (MM) are intentional movements of one limb (usually the upper one) that is involuntarily accompanied (mirrored) by the same movements of the opposite limb. Congenital MM (CMM) reflects dysfunctions and structural abnormalities of the motor network, including altered decussation of the corticospinal tract. CMM can be part of a more complex disorder such as Klippel-Feil syndrome, Kallmann syndrome, or congenital hemiplegia. Isolated CMM are autosomal dominantly inherited with incomplete penetrance. Heterozygous mutations in DCC, encoding the receptor for nectrin 1 that mediates axon guidance of developing neurons across the body's midline, have been described in patients with CMM. Recently, heterozygous RAD51 mutations have been detected in two DCC-mutation negative families. Mild MM can occur during development up to the age of 10 years causing difficulties in establishing an early clinical diagnosis. We report the case of a 19-month-old boy with CMM confirmed by genetic testing. He is the first child of healthy unrelated parents. Pregnancy, birth, postnatal adaptation, and groß motor milestones were normal; he walked without help at 15 months. At 3 months, he stretched his hands toward objects while balling his fists. He grabbed objects from age 7 months, but only with one hand at a time. When he turned objects for exploration, the other hand would turn as well. On examination at 19 months, he displayed typical MM of the hands. His cognition and speech were normal, there was no spasticity or hemiparesis, and odor discrimination seemed normal. Sequencing of the DCC gene identified heterozygous de novo 1-bp duplication (c.1999dupC/p.Arg667Profs*4).

We conclude that disclosure of a DCC or RAD51 mutation can confirm the diagnosis of CMM in infants even at an age when MM appear physiologically and transcranial magnetic stimulation (for examination of corticospinal projections) is difficult. This has important therapeutic implications as toddlers with these soft neurological signs should receive early functional uni- and bimanual training to improve their fine motor skills.