Gropman Andrea L, Duncan Wallace C, Smith Ann C M
Department of Pediatrics (Genetics and Metabolism), Georgetown University, Washington, DC 20007, USA.
Pediatr Neurol. 2006 May;34(5):337-50. doi: 10.1016/j.pediatrneurol.2005.08.018.
The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring, mental retardation and multiple congenital anomalies caused by a heterozygous interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis syndrome is characterized by a distinct pattern of features including infantile hypotonia, generalized complacency and lethargy in infancy, minor skeletal (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities, middle ear and laryngeal abnormalities including hoarse voice, as well as marked early expressive speech and language delays, psychomotor and growth retardation, and a 24-hour sleep disturbance. A striking neurobehavioral pattern of stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive and self-injurious and aggressive behavior is observed with increasing age. The diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a constellation of physical, developmental, and behavioral features in combination with a sleep disorder characterized by inverted circadian rhythm of melatonin secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy and early childhood, and become more recognizable with advancing age. Infants are described as looking "cherubic" with a Down syndrome-like appearance, whereas with age the facial appearance is that of relative prognathism. Early diagnosis requires awareness of the often subtle clinical and neurobehavioral phenotype of the infant period. Speech delay with or without hearing loss is common. Most children are diagnosed in mid-childhood when the features of the disorder are most recognizable and striking. While improvements in cytogenetic analysis help to bring cases to clinical recognition at an earlier age, this review seeks to increase clinical awareness about Smith-Magenis syndrome by presenting the salient features observed at different ages including descriptions of the neurologic and behavioral features. Detailed review of the circadian rhythm disturbance unique to Smith-Magenis syndrome is presented. Suggestions for management of the behavioral and sleep difficulties are discussed in the context of the authors' personal experience in the setting of an ongoing Smith-Magenis syndrome natural history study.
史密斯-马吉尼斯综合征是一种罕见的、复杂的多系统疾病，其特征为智力发育迟缓以及由17号染色体p11.2区域杂合性间质缺失导致的多种先天性异常。史密斯-马吉尼斯综合征的表型具有独特的特征模式，包括婴儿期肌张力减退、婴儿期普遍的自满和嗜睡、轻微的骨骼（短头畸形、短指畸形）和颅面特征、眼部异常、中耳和喉部异常（包括声音嘶哑），以及明显的早期表达性言语和语言延迟、精神运动和生长发育迟缓，还有24小时睡眠障碍。随着年龄增长，会观察到一种显著的神经行为模式，表现为刻板动作、多动、抠挖皮肤、拔甲癖、适应不良以及自伤和攻击行为。史密斯-马吉尼斯综合征的诊断基于对一系列身体、发育和行为特征的临床识别，以及以褪黑素分泌昼夜节律倒置为特征的睡眠障碍。史密斯-马吉尼斯综合征的许多特征在婴儿期和幼儿期较为细微，随着年龄增长会变得更加明显。婴儿被描述为具有类似唐氏综合征的“天使般”面容，而随着年龄增长，面部外观呈现相对突颌。早期诊断需要了解婴儿期通常较为细微的临床和神经行为表型。伴有或不伴有听力损失的言语延迟很常见。大多数儿童在童年中期被诊断出来，此时该疾病的特征最为明显和突出。虽然细胞遗传学分析的改进有助于在更早的年龄使病例得到临床识别，但本综述旨在通过呈现不同年龄阶段观察到的显著特征（包括神经和行为特征的描述）来提高对史密斯-马吉尼斯综合征的临床认识。文中详细介绍了史密斯-马吉尼斯综合征特有的昼夜节律紊乱。结合作者在正在进行的史密斯-马吉尼斯综合征自然史研究中的个人经验，讨论了行为和睡眠问题的管理建议。
