Congenital Mirror Movements

Excerpt

Clinical characteristics: The disorder of congenital mirror movements (CMM) is characterized by early-onset, obvious mirror movements (involuntary movements of one side of the body that mirror intentional movements on the opposite side) in individuals who typically have no other clinical signs or symptoms. Although mirror movements vary in severity, most affected individuals have strong and sustained mirror movements of a lesser amplitude than the corresponding voluntary movements. Mirror movements usually persist throughout life, without deterioration or improvement, and are not usually associated with subsequent onset of additional neurologic manifestations. However, a subset of affected individuals with a heterozygous pathogenic variant in DCC may have CMM with abnormalities of the corpus callosum and concomitant cognitive and/or neuropsychiatric issues.

Diagnosis/testing: The diagnosis of CMM is established in a proband with suggestive clinical findings and occasionally by identification of a heterozygous pathogenic variant in DCC, NTN1, or RAD51 by molecular genetic testing.

Management: Treatment of manifestations: Adaptation of the school environment (e.g., allocation of extra time during examinations and limitation of the amount of handwriting) is recommended. Stigmatizing children and adolescents should be avoided to assure that educational opportunities are not lost as a result of mirror movements. Adolescents and young adults should be encouraged to consider a profession that does not require complex bimanual movements, repetitive or sustained hand movements, or extensive handwriting. Standard therapy for any neurocognitive issues is recommended.

Agents/circumstances to avoid: Complex bimanual movements or sustained/repetitive hand activity in order to reduce pain or discomfort in the upper limbs.

Genetic counseling: CMM is generally inherited in an autosomal dominant (AD) manner. (Autosomal recessive inheritance has been suggested in one family.) For AD inheritance: most individuals with CMM resulting from a pathogenic variant in DCC, NTN1, or RAD51 inherited the pathogenic variant from a parent who may be symptomatic or asymptomatic. If a parent of the proband is affected and/or has a DCC, NTN1, or RAD51 pathogenic variant, the risk to the sibs of inheriting the variant is 50%. Of note, the sibs of a proband who has clinically unaffected parents are still at increased risk for CMM because of the significant possibility of reduced penetrance in a heterozygous parent. Each child of an individual with AD CMM has a 50% chance of inheriting the causative variant; however, because of reduced penetrance, offspring who inherit the pathogenic variant may not manifest CMM. Once the CMM-causing pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.