Wong Lee-Chin, Wu Yen-Tzu, Hsu Chia-Jui, Weng Wen-Chin, Tsai Wen-Che, Lee Wang-Tso
Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Front Neurol. 2019 Jun 28;10:641. doi: 10.3389/fneur.2019.00641. eCollection 2019.
-related syndrome is a rare neurodevelopmental encephalopathy characterized by early onset hyperkinetic movement disorders, absent language, autistic features, epilepsy, and severe cognitive impairment. However, detailed evaluation of cognition and evolution of movement disorders over time have not been clearly described before. In this study, we performed whole-exome sequencing in a cohort with unknown severe encephalopathy and movement disorders, with/without autistic behaviors. We identified mutations in three patients. One of them had a novel mutation that has not been described before. The neuropsychological test by Mullen Scales of Early Learning (MSEL) showed severe psychomotor impairments in all patients. There were uneven cognitive abilities in terms of verbal and non-verbal cognitive domains in all of them, with approximately 2 months differences. Gross motor skills and expressive language were more severely affected than the other domains in all the patients. All individuals had early onset hyperkinetic movement disorders. The movement disorders in one of our patients changed from predominantly hyperkinetic in early childhood to more hypokinetic in adolescence with the development of dystonia. To the best of our knowledge, this evolution had never been described before. In conclusion, individuals with -related syndrome may show clinical progression from hyperkinetic to hypokinetic features over time. There were also uneven cognitive abilities in verbal and non-verbal cognitive domains. The mutation should be considered in individuals with a history of hyperkinetic movements, microcephaly, and uneven cognitive abilities with characteristic brain images.
相关综合征是一种罕见的神经发育性脑病，其特征为早期出现多动性运动障碍、无语言能力、自闭症特征、癫痫和严重认知障碍。然而，此前尚未对认知及运动障碍随时间的演变进行过详细描述。在本研究中，我们对一组患有不明严重脑病和运动障碍、有或无自闭症行为的患者进行了全外显子组测序。我们在三名患者中发现了突变。其中一人有一个此前未被描述过的新突变。通过早期学习穆伦量表（MSEL）进行的神经心理学测试显示，所有患者均有严重的精神运动障碍。他们在言语和非言语认知领域的认知能力不均衡，相差约2个月。在所有患者中，大运动技能和表达性语言比其他领域受影响更严重。所有个体均有早期多动性运动障碍。我们其中一名患者的运动障碍从幼儿期主要的多动转变为青少年期随着肌张力障碍的发展而更多地出现运动减少。据我们所知，这种演变此前从未被描述过。总之，患有相关综合征的个体可能会随着时间推移出现从多动到运动减少特征的临床进展。在言语和非言语认知领域也存在认知能力不均衡的情况。对于有多动病史、小头畸形以及具有特征性脑影像表现且认知能力不均衡的个体，应考虑相关突变。
