The unique combination of dermatological and ocular phenotypes in Alström syndrome: severe presentation, early onset and two novel ALMS1 mutations.
The unique combination of dermatological and ocular phenotypes in Alström syndrome: severe presentation, early onset and two novel ALMS1 mutations.
复制标题
Alström 综合征皮肤病学和眼部表型的独特组合：严重的表现、早发和两种新的 ALMS1 突变。
DOI：
10.1111/j.1365-2133.2010.10157.x
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Marshall,JD
中科院分区：
文献类型：
--
作者：
Kocova,M;Sukarova-Angelovska,E;Kacarska,R;Maffei,P;Milan,G;Marshall,JD
Alström综合征（ALMS）（MIM编号203800）是一种罕见的、复杂的常染色体隐性遗传病，影响多个器官和系统。患者存在导致失明、听力受损、严重胰岛素抵抗、黑棘皮病和2型糖尿病、肥胖、婴儿期扩张型心肌病或青少年/成人发作的限制性心肌病的锥-杆营养不良。在青少年和成人中，激素失衡、胆固醇血症、成人身材矮小伴脊柱侧凸、肝脂肪变性和肝硬化、肺纤维化和肾衰竭是进行性的。低睾酮水平常见于男性，但高雄激素血症（多毛症）常见于女性患者。第二性征，如腋毛和阴毛通常在男性和女性都是正常的。各种并发症包括甲状腺功能减退、发育里程碑延迟、癫痫发作、胃肠和泌尿系统功能障碍。典型症状在整个儿童时期逐渐发作，通常会将诊断推迟到青春期或成年期。治疗是具有挑战性的，皮肤表型往往被忽视。ALMS是由ALMS 1（chr 2 p13）突变引起的。3，4细胞定位研究表明，ALMS 1蛋白广泛表达并定位于纤毛细胞的中心体和基体，5，6并且已经提出了在细胞内运输以及纤毛和中心体功能中的作用。6例12岁女性，表现为ALMS的典型表型特征，沿着重度（a）（e）（B）（c）（d）
MADAM, Alström syndrome (ALMS)(MIM no. 203800) is a rare, complex, autosomal recessive genetic disorder affecting multiple organs and systems. Patients present with cone-rod dystrophy leading to blindness, hearing impairment, severe insulin resistance, acanthosis nigricans, and type 2 diabetes, obesity, dilated cardiomyopathy in infancy, or adolescent⁄ adult-onset restrictive cardiomyopathy. Hormonal imbalances, hyperlipidaemia, short adult stature with scoliosis, liver steatosis and cirrhosis, pulmonary fibrosis and renal failure is progressive in adolescents and adults. Low testosterone levels are frequently observed in males, but hyperandrogenism (hirsutism) is often reported in female patients. Secondary sexual characteristics such as axillary and pubic hair are usually normal in both males and females. Variable complications can include hypothyroidism, delay of developmental milestones, seizures, gastrointestinal and urological dysfunction. 1, 2 The gradual onset of the classic symptoms throughout childhood often delays the diagnosis until adolescence or adulthood. Treatment is challenging and the dermatological phenotypes are often overlooked. ALMS is caused by mutations in ALMS1 (chr 2p13). 3, 4 Cellular localization studies have shown that the ALMS1 protein is ubiquitously expressed and localizes to centrosomes and basal bodies of ciliated cells, 5, 6 and roles in intracellular transport and ciliary and centrosomal function have been suggested. 6 A 12-year-old female presented with classic phenotypic characteristics of ALMS, along with presentation of severe (a)(e)(b)(c)(d)