Méneret Aurélie, Trouillard Oriane, Dunoyer Margaux, Depienne Christel, Roze Emmanuel
Département de Neurologie, Hôpital de la Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris;, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau, UPMC Sorbonne Universités, Paris, France
INSERM U 1127, CNRS UMR 7225, Institut du Cerveau, UPMC Sorbonne Universités;, Sorbonne Université, INSERM, CNRS, Institut de Biologie Paris Seine, Neuroscience Paris Seine, Paris, France
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 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 , , or by molecular genetic testing.
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. Complex bimanual movements or sustained/repetitive hand activity in order to reduce pain or discomfort in the upper limbs.
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 , , or 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 , , or 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.
先天性镜像运动障碍（CMM）的特点是起病早，个体出现明显的镜像运动（身体一侧的非自主运动，与对侧的自主运动相对应），且通常无其他临床体征或症状。尽管镜像运动的严重程度各不相同，但大多数受影响个体的镜像运动强烈且持续，幅度小于相应的自主运动。镜像运动通常终生持续，无恶化或改善，通常也不伴有随后出现的其他神经学表现。然而，一部分在[相关基因]中有杂合致病变异的受影响个体可能患有伴有胼胝体异常以及认知和/或神经精神问题的CMM。
诊断/检测：CMM的诊断基于先证者的提示性临床发现，偶尔也通过分子基因检测在[相关基因]中鉴定出杂合致病变异来确诊。
建议对学校环境进行调整（例如，考试时额外分配时间，限制书写量）。应避免使儿童和青少年受到污名化，以确保不因镜像运动而失去教育机会。应鼓励青少年和年轻人考虑选择不需要复杂双手运动、重复性或持续性手部运动或大量书写的职业。对于任何神经认知问题，建议采用标准治疗方法。为了减轻上肢疼痛或不适，避免进行复杂的双手运动或持续性/重复性手部活动。
CMM通常以常染色体显性（AD）方式遗传。（在一个家族中曾提示常染色体隐性遗传。）对于AD遗传：大多数由[相关基因]中的致病变异导致CMM的个体从可能有症状或无症状的父母那里遗传了该致病变异。如果先证者的父母受影响和/或有[相关基因]的致病变异，其同胞继承该变异的风险为50%。值得注意的是，先证者的父母临床未受影响时，其同胞患CMM的风险仍然增加，因为杂合父母中存在显著的外显率降低可能性。患有AD型CMM的个体的每个孩子都有50%的机会继承致病变异；然而，由于外显率降低，继承致病变异的后代可能不表现出CMM。一旦在受影响的家庭成员中鉴定出导致CMM的致病变异，就可以进行产前和植入前基因检测。
