A Case of Syphilitic Keratoderma Concurrent with Syphilitic Uveitis

Syphilitic keratoderma is a rare cutaneous manifestation of secondary syphilis, characterized by symmetrical and diffuse hyperkeratosis of the palms and soles. In addition, no cases of syphilitic keratoderma and uveitis have been reported in the dermatologic literature. A 69-year-old woman presented with steroid-resistant hyperkeratotic patches on the palms and soles and uveitis for 4 months. As steroid-resistant uveitis must be evaluated for syphilis, viral infections, and autoimmune diseases, we ran several laboratory tests and the serologic test for VDRL was reactive (titer; 1:128). After treatment with penicillin G (4 MU, IV every 4 hours for 2 weeks), her skin lesions and visual disturbance were completely resolved. Therefore she was diagnosed as having syphilitic keratoderma and uveitis. Here, we report a rare case of syphilitic keratoderma concurrent with syphilitic uveitis and suggest that evaluation for syphilis may be required when skin lesions and ocular disturbance are resistant to long-term steroid therapy.     

一个表皮松解性掌跖角化病家系的KRT1基因突变分析

目的 探讨一个中国汉族人表皮松解性掌跖角化病(EPPK)家系的角蛋白基因KRT1、KRT9、KRT10突变情况.方法 收集1个EPPK家系的临床资料,提取外周血DNA,通过PCR扩增角蛋白KRT1、KRT9、KRT10基因编码区的全部外显子及其侧翼序列并测序,以表型正常家系成员及50例健康人为正常对照.结果 发现家系内6例患者均存在KRT1基因错义突变c.1436T>C,导致第479位的异亮氨酸被苏氨酸取代(I479T),在家系中6例正常人及50例对照者未发现上述突变.结论 错义突变KRTI的c.1436T>C可能为导致该家系临床表型的主要原因.本例为国内首次发现的KRT1突变引起的EPPK家系.

Abstract：

Objective To analyze the mutations in keratin 1 (KRT1), KRT9 and KRT10 genes in a Chinese family with epidermolytic palmoplantar keratoderma (EPPK). Methods Clinical data were collected from a family with EPPK. Genomic DNA was extracted from the peripheral blood of 12 family members, including 6 patients and 6 unaffected members, as well as from 50 unrelated normal human controls. PCR was performed to amplify all the exons and flanking sequences of KRT1, KRT9 and KRT10 genes followed by DNA sequencing.Results A missense mutation C.1436T > C was found in the highly conserved helix termination motif of KRT1 gene of all the patients, resulting in a substitution of isoleucine by threonine at position 479 of the KRT1 protein. No mutation was found in the unaffected members or unrelated controls. Conclusions The missense mutation C.1436T > C in K.RT1 gene is likely to be the main cause of the phenotype of EPPK in this family.This is the first report of a pedigree with KRT1 gene mutation-induced EPPK in China.     

母女同患Olmste综合征

例1女,2月龄,全身起角化性斑块近2个月。体检：眶周、口周、外阴、肛周可见片状境界较清楚角化性暗红色斑块,厚层鳞屑,局部见轻度浸渍,双足及双手掌可见黄色厚痂、皲裂。例2女,例1的母亲,24岁,口周、肛周角化性斑块,先天性普秃,双手足指(趾)残毁至指(趾)末端,残毁端见大量黄色肥厚性、角化性痂屑。例1臀部皮损组织病理检查：表皮呈银屑病样增生,真皮乳头及浅层血管周围可见不等量炎性细胞浸润。免疫组化：AE1在表皮棘层颗粒层染色阳性,CK10在棘层上部和颗粒层阳性。电镜检查：细胞间距增大,张力丝减少。诊断：母女同患Olmsted综合征。     

一残毁性掌跖角化病家系GJB2基因突变研究

目的 对一个中国汉族残毁性掌跖角化病家系进行GJB2基因突变检测,以明确其致病基因。 方法 收集该家系5例患者、4例正常人和100例非该家系成员外周血和家系患者临床资料。提取基因组DNA,PCR扩增包括GJB2基因整个编码序列在内的1015 bp,扩增产物纯化后应用ABI PRISM 3730XL自动测序仪直接双向测序, Sequencher 4.10.1 Demo 软件与基因组序列进行比对分析,查找有无突变基因。结果 该家系所有患者GJB2基因均存在一个杂合错义突变196G→C,导致第一细胞外区域（E1）第66位天冬氨酸被组氨酸替代（即D66H）,而家系中4例正常人和100例非家系成员正常人对照的DNA测序结果均未发现此突变。结论 GJB2基因中D66H错义突变是中国汉族人群中残毁性掌跖角化伴耳聋的致病原因之一。     

残毁性掌跖角化病一例

患者20岁，女性，从2岁起掌跖皮肤出现红斑、增厚伴脱屑并逐渐加重，12岁时左手示指甲脱落并发生指背溃疡，溃疡无疼痛和压痛。目前双手拇指节末端杵样膨大。食指缩短，中指伸侧有蜂窝状凹陷，各手指关节伸侧对称性分布暗红色角化性斑疹；手掌合拢困难；足趾角化增厚边缘附黄色鳞屑，足跖部见胼胝样角化增厚斑块；皮损无瘙痒感。结合X线、实验室和组织病理检查，诊断为残毁性掌跖角化病。给予阿维A治疗，疗效较好，并对患者进行了长期随访。     

三个表皮松解性掌跖角化症家系KRT9基因突变的研究

目的 探讨表皮松解性掌跖角化症家系的KRT9基因突变与临床表现的关系。方法 PCR扩增KRT9基因编码氨基酸的7个外显子,对扩增产物进行变性高效液相色谱分析、DNA测序。结果 在所研究的3个EPPK家系中,发现KRT9基因第1外显子第497位核苷酸A缺失并插入GGCT,导致角蛋白9分子第166位酪氨酸缺失并插入色氨酸和亮氨酸,即Y166delinsWL。片段特异性PCR证实了该突变不是一个常见的多态性,而是国际中间纤维突变库(http://www.interfil.org)中未报道过的一种新突变。结论 KRT9基因497delAinsGGCT突变可能是部分中国人EPPK患者发病的遗传基础。     

Composite keratohyaline granules in striate keratoderma

The gross, light microscopic, and ultrastructural findings in a 55 year old man was striate keratoderma are presented. There was no family history of the disease. The lesions developed in his late teens and early adult years, and consisted of progressively worsening, raised, hyperkeratotic, linear plaques on the palm and volar surface of the third and fifth fingers bilaterally. There were also painful callositieson both heels, and thick, raised plaques on the heels and lateral plantar surfaces. The epidermis was papillomatous and acanthotic, with marked orthokeratosis, minimal parakeratosis, and a very thickened granular layer. No epidermolysis was seen. Electron microscopy showed increased tonofibrils in the stratum spinosum arranged in wavy, parallel bundles and a granular layer in which normal Odland bodies were present. However, the keratohyaline granules were large, with rounded bordersand a striped, alternating, dark and light content characteristic of composite granules. There was diminished contact of the granules with tonofibrils. The transition to the stratum corneum was abrupt. The ultrastructural and genetic features of keratodermas, with special emphasis on the striate type, are reviewed.     

X连锁鱼鳞病并发Meleda角化病一例临床特征及SLURP-1和STS基因突变分析

目的 报道1例X连锁鱼鳞病并发Meleda角化病,并检测其基因突变.方法 收集临床资料,提取患儿及其父母外周血基因组DNA,PCR扩增SLURP-1和STS基因全部外显子及其侧翼序列,以100例健康人作为对照,对扩增产物行琼脂糖凝胶电泳检测,并对SLURP-1基因扩增产物进行DNA测序.结果 患儿躯干、四肢泛发规则排列的棕褐色或黑色多角形鳞屑,掌跖、肘膝、腹股沟、肛周红斑,过度角化,向背侧延伸,诊断为X连锁鱼鳞病并发Meleda角化病.基因检测提示,STS全基因缺失;SLURP-1基因第3外显子第286位核苷酸发生C→T纯合突变(c.286C＞T),导致其编码蛋白质在第96位氨基酸出现终止改变(p.R96*),其父母均为c.286C＞T杂合突变携带者.健康对照未发现此突变.结论 该患者携带STS全基因缺失和SLURP-1基因纯合无义突变,可能是导致X连锁鱼鳞病并发Meleda角化病的原因.     

Exuberant clinical picture of Buschke-Fischer-Brauer palmoplantar keratoderma in bedridden patient

Buschke-Fisher-Brauer keratoderma is a rare hereditary autosomal dominant disease of incomplete penetrance. Important differential diagnoses include other palmoplantar keratinization disorders, acquired or hereditary, which is done based on the histopathological findings. This diagnosis alerts especially about the possibility of associated neoplasms. Treatment involves topical keratolytic agents, usually with little efficacy, or with long-term systemic retinoids with follow-up of exuberant collateral effects.     

CEDNIK syndrome in a Brazilian patient with compound heterozygous pathogenic variants

CEDNIK (Cerebral Dysgenesis, Neuropathy, Ichthyosis, and Keratoderma) syndrome is a neuro ichthyotic syndrome characterized by a clinical constellation of features including severe developmental delay, microcephaly, and facial dysmorphism. Here, we report the clinical and molecular characterization of a patient with CEDNIK syndrome harboring two compound heterozygous variants in the SNAP29 gene. The patient presents a combination of a loss-of-function SNAP29 mutation and a ～370 kb 22q11.2 deletion, each of these genetic variants inherited from one of the parents. This report provides detailed data of a patient with unprecedented genetic events leading to the CEDNIK phenotype and may contribute to the elucidation of this rare condition.