Wang Tzong-Shi, Tsai Wen-Hsin, Tsai Li-Ping, Wong Shi-Bing
Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.
Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan.
Tzu Chi Med J. 2019 Oct 31;32(2):137-144. doi: 10.4103/tcmj.tcmj_103_19. eCollection 2020 Apr-Jun.
Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are considered sister imprinting disorders. Although both AS and PWS congenital neurodevelopmental disorders have chromosome 15q11.3-q13 dysfunction, their molecular mechanisms differ owing to genomic imprinting, which results in different parent-of-the-origin gene expressions. Recently, several randomized controlled trials have been proceeded to treat specific symptoms of AS and PWS. Due to the advance of clinical management, early diagnosis for patients with AS and PWS is important. PWS is induced by multiple paternal gene dysfunctions, including those in MKRN3, MAGEL2, NDN, SNURF-SNPRPN, NPAP1, and a cluster of small nucleolar RNA genes. PWS patients exhibit characteristic facial features, endocrinological, and behavioral phenotypes, including short and obese figures, hyperphagia, growth hormone deficiency, hypogonadism, autism, or obsessive- compulsive-like behaviors. In addition, hypotonia, poor feeding, failure to thrive, and typical facial features are major factors for early diagnosis of PWS. For PWS patients, epilepsy is not common and easy to treat. Conversely, AS is a single-gene disorder induced by ubiquitin-protein ligase E3A dysfunction, which only expresses from a maternal allele. AS patients develop epilepsy in their early lives and their seizures are difficult to control. The distinctive gait pattern, excessive laughter, and characteristic electroencephalography features, which contain anterior-dominated, high-voltage triphasic delta waves intermixed with epileptic spikes, result in early suspicion of AS. Often, polytherapy, including the combination of valproate, levetiracetam, lamotrigine, and benzodiazepines, is required for controlling seizures of AS patients. Notably, carbamazepine, oxcarbazepine, and vigabatrin should be avoided, since these may induce nonconvulsive status epilepticus. AS and PWS presented with distinct clinical manifestations according to specific molecular defects due to genomic imprinting. Early diagnosis and teamwork intervention, including geneticists, neurologists, rehabilitation physicians, and pulmonologists, are important. Epilepsy is common in patients with AS, and after proper treatment, seizures could be effectively controlled in late childhood or early adulthood for both AS and PWS patients.
天使综合征（AS）和普拉德-威利综合征（PWS）被认为是姊妹印记障碍。尽管AS和PWS这两种先天性神经发育障碍都存在15q11.3-q13染色体功能障碍，但由于基因组印记，它们的分子机制有所不同，这导致了不同亲本来源基因的表达。最近，已经开展了几项随机对照试验来治疗AS和PWS的特定症状。由于临床管理的进步，对AS和PWS患者进行早期诊断很重要。PWS是由多种父源基因功能障碍引起的，包括MKRN3、MAGEL2、NDN、SNURF-SNPRPN、NPAP1以及一组小核仁RNA基因中的功能障碍。PWS患者表现出特征性的面部特征、内分泌和行为表型，包括身材矮小和肥胖、食欲亢进、生长激素缺乏、性腺功能减退、自闭症或强迫样行为。此外，肌张力低下、喂养困难、生长发育迟缓以及典型的面部特征是PWS早期诊断的主要因素。对于PWS患者来说，癫痫并不常见且易于治疗。相反，AS是一种由泛素蛋白连接酶E3A功能障碍引起的单基因疾病，该基因仅从母本等位基因表达。AS患者在早年就会发生癫痫，且他们的癫痫发作难以控制。独特的步态模式、过度大笑以及特征性的脑电图特征，包括以额叶为主的、高压三相δ波与癫痫棘波混合，导致早期怀疑为AS。通常，控制AS患者的癫痫发作需要多种药物联合治疗，包括丙戊酸盐、左乙拉西坦、拉莫三嗪和苯二氮䓬类药物的联合使用。值得注意的是，应避免使用卡马西平、奥卡西平和氨己烯酸，因为这些药物可能诱发非惊厥性癫痫持续状态。由于基因组印记导致的特定分子缺陷，AS和PWS表现出不同的临床表现。早期诊断以及包括遗传学家、神经科医生、康复医生和肺科医生在内的团队合作干预很重要。癫痫在AS患者中很常见，经过适当治疗后，AS和PWS患者在儿童晚期或成年早期的癫痫发作都可以得到有效控制。
