Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Familial Risk Clinic, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal.
Am J Med Genet A. 2019 Nov;179(11):2237-2240. doi: 10.1002/ajmg.a.61303. Epub 2019 Jul 26.
Woodhouse-Sakati Syndrome is a very rare autosomal recessive disorder caused by pathogenic variants in the DCAF17 gene, which encodes DDB1- and CUL4-associated factor 17. It is a multisystemic disorder characterized by hypogonadism, adolescent- to young adult-onset diabetes mellitus, hypothyroidism, and alopecia. Neurologic involvement includes childhood-onset moderate bilateral sensorineural hearing loss, mild intellectual disability adolescent- to young adult-onset of extrapyramidal findings, dysarthria, and dysphagia. Brain imaging typically reveals iron deposition in the globus pallidus and periventricular leukodystrophy. We report the case of a 31-year-old Portuguese female, the only child of a consanguineous couple. She presented with cognitive impairment, spastic paraparesis, lower limb dystonia, dysarthria, and dysphagia. She also had hypergonadotrophic hypogonadism associated with primary amenorrhea, insulin-dependent diabetes mellitus with retinopathy, primary hypothyroidism, moderate bilateral sensorineural hearing loss, and alopecia. Serial brain magnetic resonance imaging showed a progressive periventricular leukodystrophy with pontine involvement and significant bilateral iron deposition in the globus pallidus, substantia nigra, and red nucleus. The diagnosis of Woodhouse-Sakati Syndrome was eventually proposed and DCAF17 gene sequencing identified a novel likely pathogenic homozygous variant NG_013038.1(NM_025000.3):c.1091+2T>C. Genetic testing allowed a more accurate prognosis and a precise genetic counseling for our patient's family.
伍德豪斯-萨卡蒂综合征是一种非常罕见的常染色体隐性遗传病，由 DCAF17 基因的致病性变异引起，该基因编码 DDB1 和 CUL4 相关因子 17。它是一种多系统疾病，其特征为性腺功能减退、青少年至成年发病的糖尿病、甲状腺功能减退和脱发。神经病变包括儿童期起病的双侧中度感觉神经性听力损失、轻度智力障碍、青少年至成年发病的锥体外系表现、构音障碍和吞咽困难。脑部影像学通常显示苍白球铁沉积和脑室周围白质营养不良。我们报告了一例 31 岁的葡萄牙女性，是一对近亲夫妇的独生女。她表现为认知障碍、痉挛性截瘫、下肢肌张力障碍、构音障碍和吞咽困难。她还患有高促性腺激素性性腺功能减退症，伴原发性闭经、伴有视网膜病变的胰岛素依赖型糖尿病、原发性甲状腺功能减退症、双侧中度感觉神经性听力损失和脱发。连续脑部磁共振成像显示进行性脑室周围白质营养不良，伴有桥脑受累和明显的双侧苍白球、黑质和红核铁沉积。最终提出了伍德豪斯-萨卡蒂综合征的诊断，DCAF17 基因测序发现了一种新的可能致病的纯合变异 NG_013038.1(NM_025000.3):c.1091+2T>C。遗传测试为我们的患者家庭提供了更准确的预后和精确的遗传咨询。
