Olmsted syndrome: clinical, molecular and therapeutic aspects.
Olmsted syndrome: clinical, molecular and therapeutic aspects.
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DOI：
10.1186/s13023-015-0246-5
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发表时间：
2015-03-17
影响因子：
3.7
通讯作者：
Hovnanian A
中科院分区：
文献类型：
--
作者：
Duchatelet S;Hovnanian A
Olmsted综合征（OS）是一种罕见的遗传性皮肤病，其典型特征为双侧毁损性跨性别掌跖角化病（PPK）和掌周角化斑块，但其临床表现具有相当大的异质性。这种疾病通常在出生或幼儿期开始。全世界报告了大约73例病例。在两种性别中均观察到OS，但男性病例更常见。大多数提示性症状与PPK伴假性隐球菌和角膜周围角化斑有关。常见的相关特征包括毛发和指甲异常、白细胞角化病、角膜默认和复发性感染。疼痛和瘙痒是可变的，但可能很严重。大多数报告的OS病例是散发的，尽管也描述了具有不同遗传方式的家族性病例。TRPV 3（Transient receptor potential vanilloid-3）基因突变是常染色体显性（功能获得性突变）或隐性OS的原因。MBTPS 2（membrane-bound transcription factor protease，site 2）基因突变是隐性X连锁突变。诊断主要依赖于与严重PPK和角膜周围角化斑块相关的临床特征，但在具有不完全表型或非典型特征的患者中可能具有挑战性。OS必须与其他严重形式的PPK相鉴别，包括Vohwinkel、Clouston、Papillon-Lefèvre或Haim-Munk综合征、Mal de Meleda、先天性甲肥厚、酪氨酸血症II型和肠病性肢端皮炎。当鉴别诊断难以排除时，遗传学研究对于寻找TRPV 3或MBTPS 2突变至关重要。然而，其他基因仍有待鉴定。目前没有具体的和令人满意的治疗可用于OS。目前的治疗角化过度（主要是润肤剂，角质层溶解剂，类维生素A或皮质类固醇），无论是局部或全身，症状，并提供只有暂时的部分缓解。疼痛和瘙痒的具体管理是重要的，以减少疾病的发病率。这种疾病会使人衰弱，并且进行性角化病和手指自动截肢会阻止患者抓握和行走，并将他们限制在轮椅上。因此，新的治疗选择是至关重要的，并预计从更好地了解疾病的机制。TRPV 3拮抗剂的使用将代表这样的靶向和潜在的强大策略。
Olmsted syndrome (OS) is a rare genodermatosis classically characterized by the combination of bilateral mutilating transgredient palmoplantar keratoderma (PPK) and periorificial keratotic plaques, but which shows considerable clinical heterogeneity. The disease starts usually at birth or in early childhood. About 73 cases have been reported worldwide. OS is observed in both sexes, although male cases are more frequent. The most suggestive symptoms associate PPK with pseudoainhum and periorificial keratotic plaques. Frequently associated features include hair and nail abnormalities, leukokeratosis, corneal default and recurrent infections. Pain and itching are variable but can be severe. Most of reported OS cases are sporadic, although familial cases with different mode of inheritance were also described. Mutations in TRPV3 (Transient receptor potential vanilloid-3) gene have recently been identified as a cause of autosomal dominant (gain-of-function mutations) or recessive OS. Mutations in MBTPS2 (membrane-bound transcription factor protease, site 2) gene were identified in a recessive X-linked form. The diagnosis relies mainly on clinical features associating severe PPK and periorificial keratotic plaques, but can be challenging in patients with incomplete phenotype or atypical features. OS has to be differentiated from other severe forms of PPK including Vohwinkel, Clouston, Papillon-Lefèvre or Haim-Munk syndromes, Mal de Meleda, pachyonychia congenita, Tyrosinemia type II and acrodermatitis enteropathica. When differential diagnoses are difficult to exclude, genetic studies are essential to search for a TRPV3 or MBTPS2 mutation. However, additional genes remain to be identified. No specific and satisfactory therapy is currently available for OS. Current treatments of hyperkeratosis (mainly emollients, keratolytics, retinoids or corticosteroids), either topical or systemic, are symptomatic and offer only temporary partial relief. Specific management of pain and itching is important to reduce the morbidity of the disease. The disease is debilitating and progressive keratoderma and auto-amputation of digits can prevent patients from grasping and walking, and confine them to a wheelchair. New therapeutic options are therefore crucial and are expected from a better understanding of the disease mechanisms. The use of TRPV3 antagonists would represent such a targeted and potentially powerful strategy.
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DOI：
10.1523/jneurosci.5741-07.2008
发表时间：
2008-12-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Huang SM;Lee H;Chung MK;Park U;Yu YY;Bradshaw HB;Coulombe PA;Walker JM;Caterina MJ
通讯作者：
Caterina MJ
DOI：
10.1159/000249320
发表时间：
1986-03-01
期刊：
DERMATOLOGICA
影响因子：
--
作者：
HARMS, M;MASOUYE, I;RADEFF, B
通讯作者：
RADEFF, B
影响因子：
4.1
作者：
Al-Mutairi, N;Sharma, AK;Al-Adawy, E
通讯作者：
Al-Adawy, E
影响因子：
1.5
作者：
Bergonse, FN;Rabello, SM;Rivitti, EA
通讯作者：
Rivitti, EA
影响因子：
2.3
作者：
Dessureault, J;Poulin, Y;Gagne, E
通讯作者：
Gagne, E