Squamous cell carcinoma arising in CHILD syndrome

Congenital hemidysplasia with ichthyosiform naevus and limb defects (CHILD) syndrome is a rare X-linked dominant disorder. The first case of squamous cell carcinoma arising within the affected ichthyosiform skin in a 33-year-old woman is reported.     

CHILD syndrome with mild skin lesions: histopathologic clues for the diagnosis

CHILD syndrome is an acronym signifying congenital hemidysplasia with ichthyosiform nevus and limb defects. A 27‐year‐old woman presented with chronic verrucous and hyperkeratotic skin lesions involving the left genital area, left hand and left foot since childhood. The histopathologic findings were consistent with verruciform xanthoma. In correlation with the clinical picture of a linear lesion, the diagnosis of CHILD nevus was made. Subsequent genetic analysis identified a germline c.324C>T (p.A105V) NSDHL mutation and confirmed a diagnosis of CHILD syndrome. This syndrome can be associated with only minimal clinical symptoms. The anatomical distribution of the lesions, a static clinical course and the typical histopathologic features of a CHILD nevus can serve as the clue to a diagnosis of CHILD syndrome in such cases.     

CHILD综合征的临床、病理及免疫组化特征

患者女,9岁.左侧躯体皮肤红色斑丘疹、斑块伴左下肢畸形9年就诊.体检:患者跛行左下肢较右侧明显短小,左足2、3、4趾畸形.左侧肢体肌张力下降,肌力较对侧弱.皮肤科检查:左侧后颈部、臀部、会阴部、小腿、足部明显红色肥厚性斑块.皮损组织病理检查:表皮角化过度,真皮乳头少量泡沫细胞浸润,真皮浅层灶性淋巴细胞和浆细胞浸润.免疫组化检查:真皮乳头泡沫细胞CD68、CD163强阳性,但不表达S100.诊断为CHILD综合征.     

Extra nuchal-type fibroma associated with elastosis, traumatic neuroma, a rare APC gene missense mutation, and a very rare MUTYH gene polymorphism: a case report and review of the literature*

We report a case of an extra nuchal-type fibroma in a 51-year-old male suspected to have attenuated familial adenomatous polyposis (Gardner's syndrome), who presented with a longstanding buttock mass excised due to enlargement and pain. Histopathologically, lobules of haphazard, hypocellular, hyalinized collagen bundles replaced the dermis and subcutis and entrapped nerve bundles, mimicking Morton neuroma. Ramifying nerve twigs found around larger nerve fascicles showed the co-existence of traumatic neuroma. Elastic tissue stain revealed elastosis characterized by large, arborizing fibers lying between and within the hyalinized collagen bundles. Modified Masson's trichrome stain showed light blue staining of collagen bundles producing the hyalinized nodules with irregular, light red staining of collagen bundles at their periphery and within tumor collagen. Compression and/or degeneration of collagen and secondary elastosis with later entrapment by tumor collagen could explain this microscopic phenotype. By immunohistochemistry, tumor spindle cells expressed nuclear β-catenin and cyclin D1, mostly within regions of fibrosis implicating activation of the adenomatous polyposis coli (APC)-Wnt pathway. Genetic analysis showed a missense mutation in APC gene (c.7504G>A, p.G2502S in exon 15) and a functional homozygous polymorphism in the MUTYH gene (c.36+325G>C, (IVS1+5G/C)). Nuchal-type fibroma has been associated with Gardner's syndrome and trauma. In this patient, genetic predisposition coupled with repetitive, localized trauma and collagen degeneration may have provided the stimulus for the development of extra nuchal-type fibroma.     

Epidermal nevus syndromes: New insights into whorls and swirls

Knowledge of the molecular underpinnings of many epidermal nevi and epidermal nevus syndrome has expanded rapidly in recent years. In this review and update on epidermal nevus syndrome, we will cover recent genetic discoveries involving epidermal nevi, including nevus sebaceus, keratinocytic epidermal nevus, nevus comedonicus, congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome, phakomatosis pigmentokeratotica, Becker's nevus, porokeratotic adnexal ostial nevus, inflammatory linear verrucous epidermal nevi, and cutaneous‐skeletal hypophosphatemia syndrome. We will discuss how newly defined mutations relate to the biology reflected in the cutaneous patterns seen in these mosaic disorders and how new molecular data has informed our understanding of these diseases and shaped management decisions.     

一例Bjornstad综合征患儿BCS1L基因突变检测

目的：检测Bjornstad综合征患儿的基因突变。方法：提取患儿，其表型正常父母及100名正常人的外周血DNA，采用二代皮肤靶向测序包检测患儿的基因突变，然后应用Sanger测序方法进行验证。结果：测序结果发现患儿及其父母在BCS1L基因存在2个杂合突变，在第7个外显子上发现c.818delC缺失突变，在第8个外显子上发现c.917G>A错义突变。健康对照中未检测到BCS1L基因突变。结论：该患儿存在BCS1L基因突变，可能与Bjornstad综合征发病有关。     

一先天性秃发家系HR和CDSN基因突变的筛查

目的：对山东省一5代30人的先天性秃发家系进行HR、CDSN基因的突变筛查，以期寻找致病基因。方法：收集家系成员的临床资料及血液样本，抽提外周血基因组DNA，进行PCR扩增，采用虾碱性磷酸酶及核酸外切酶对扩增产物进行纯化，然后用ABI PRISM 3700自动测序仪进行测序，最后用Autoassembler软件与基因组序列对比，查找有无突变。结果：未发现突变。但找到12个多态位点，其中11个是首次发现，结论：HR、CDSN基因可能与本先天性秃发家系无关。     

Progressive hyperpigmentation and generalized lentiginosis without associated systemic symptoms: a rare hereditary pigmentation disorder in south-east Germany

Familial progressive hyperpigmentation is rarely described in the literature. We report on five patients from three different families presenting with a peculiar progressive pigmentary disorder. The patients show a progressive diffuse, partly blotchy, hyperpigmentation, intermixed with scattered small hypopigmented macules, a few large hypopigmented areas, occasional café-au-lait spots and, most remarkably, a generalized lentiginosis. Histology revealed different degrees of basal layer hyperpigmentation and pigment incontinence, also in the spots appearing hypopigmented. Ultrastructural analysis showed a normal mode of Caucasian-like melanogenesis with varying content of regular melanosome complexes within the keratinocytes. All families are clustered in a small area around the town of Teublitz in south-east Germany with about 20,000 inhabitants, suggesting a genetic founder effect. Pedigree analysis is compatible with an autosomal dominant mode of inheritance with variable penetrance. Only a few similar, but not identical, cases have been reported in the past. This cluster of cases may therefore represent a rare and perhaps novel variant of a familial progressive disorder of hyperpigmentation.     

Association between the leptin gene 2548G/A polymorphism, the plasma leptin and the metabolic syndrome with psoriasis

Abstract: Background: Psoriasis is a disorder with genetic and immunologic background. Leptin can regulate the T‐helper response. Objective: Our primary goal is to study the functional polymorphism (G‐2548A) of the leptin (LEP) gene in the genetic predisposition of psoriasis, and our secondary goal is to examine factors affecting plasma leptin levels in psoriasis and to compare patients with and without metabolic syndrome (MS). Methods: The study involved 94 patients with psoriasis and 100 healthy controls. Analysis of G‐2548A polymorphism of the LEP gene was made by the PCR and restriction fragment length polymorphism technique. The relationship between LEP gene polymorphism and the clinical features of the patients was analysed. Plasma leptin levels and proportions of comorbidities in patients vs controls were compared. Results: In controls, the GA, AA and GG frequencies were 50%, 30% and 20%, respectively, while in patients, the distribution of genotypes was 42.5%, 20.2% and 38.3%, respectively, with significant difference (P = 0.014) between patients and controls. In patients with MS, the GG, GA and AA frequencies were 61.5%, 23.1% and 15.4%, respectively, while in patients without MS, the distribution of genotypes was 29.4%, 50% and 20.6%, respectively, with significant difference (P = 0.014) between both groups. Plasma leptin showed a significant higher levels in the patients versus the controls (P < 0.001), and among the different LEP genotypes (P < 0.001) in the patients’ group. Conclusion: LEP G‐2548A polymorphism could be a predictor for higher plasma leptin and increased risk of psoriasis and could be used as a marker for psoriasis‐related comorbidity risk.     

罕见突变引起的早老症1例及文献回顾

报告1例早老症。患儿男,2个月。1个月时开始出现躯干及四肢皮肤硬化、双眼突出、面部皮肤菲薄、头皮静脉显露、哭声尖细、关节僵硬和生长受限,随访过程中出现脱发。基因分析显示核纤层蛋白A基因(LMNA)突变(c.1968+1GA)。根据临床表现和基因分析结果,诊断为早老症。该位点突变引起的早老症为国内首例报告。     

New mutation in the CYLD gene within a family with Brooke‐Spiegler syndrome

Brooke‐Spiegler syndrome is a rare, autosomal dominant disease characterized by multiple skin appendage tumors caused by various mutations in the CYLD gene on chromosome 16q12‐q13. We describe a family, in which we performed a molecular‐genetic examination and found a new mutation in exon 19 in the CYLD gene leading to a frameshift. It is important to be aware of this syndrome and its pathogenesis as its phenotypic features can vary so that apparently different diseases are caused by the same genetic defect. In addition, there may be malignant transformation of the generally benign tumors, so that a timely diagnosis is essential for appropriate monitoring and therapy.     

EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome: heterozygous mutation in the p63 gene (R279H) and DNA-based prenatal diagnosis

BACKGROUND: Germline mis-sense mutations in the DNA-binding domain of the p63 gene have recently been established as the molecular basis for the autosomal dominant EEC (Ectrodactyly, Ectodermal dysplasia, Clefting) syndrome. OBJECTIVES: To examine genomic DNA from a 36-year-old woman, her 58-year-old father and her 11-year-old son, all with the EEC syndrome, to determine the inherent p63 mutation and, after genetic counselling, to use knowledge of the mutation to undertake a first-trimester DNA-based prenatal diagnosis in a subsequent pregnancy. METHODS: Fetal DNA was extracted from chorionic villi and used to amplify exon 7 of p63 containing the potential mutation. Direct sequencing and restriction endonuclease digestion (loss of AciI site on mutant allele) were used for DNA-based prenatal diagnosis. RESULTS: We identified a heterozygous arginine to histidine p63 mutation, R279H, in all three affected individuals. Prenatal diagnosis demonstrated a homozygous wild-type sequence predicting an unaffected child: a healthy boy was subsequently born at full-term. CONCLUSIONS: These data expand the p63 gene mutation database and provide the first example of a DNA-based prenatal test in this ectodermal dysplasia syndrome.     

一例Kindler综合征患者皮损超微结构及FERMT1基因突变分析

目的 检测1例Kindler综合征患者皮损超微结构改变以及FERMT1基因突变。方法 收集患者临床资料,取患处皮肤进行透射电镜检查明确其超微结构的变化。提取患者及其相关亲属外周血DNA,采用PCR扩增FERMT1基因编码区的全部外显子及其侧翼序列并测序。结果 患者皮损电镜检查显示致密板高度复制;基因检测发现患者FERMT1基因9号内含子剪切位点发生IVS9 + 1G > A纯合突变,父母为相应突变的杂合携带者,50例无关正常对照者未见该突变。结论 透射电镜可作为Kindler综合征患者确诊的辅助检查之一;FERMT1基因9号内含子剪切位点发生IVS9 + 1G > A纯合突变可能为引起该患者临床表现的病因。     

The concomitant occurrence of multiple epidermal cysts, osteomas and thyroid gland nodules is not diagnostic for Gardner syndrome in the absence of intestinal polyposis: a clinical and genetic report

Gardner syndrome, a phenotypic variant of familial adenomatous polyposis, is characterized by the classical clinical triad of skin and soft tissue tumours, osteomas and intestinal polyposis, but disease patterns with pairs of these findings have also been reported. Different mutations in the adenomatous polyposis coli (APC) gene have been shown to be associated with Gardner syndrome disease phenotypes. A 36-year-old patient presented with multiple epidermal cysts on the face, left ear lobe and neck, and the possible diagnosis of Gardner syndrome was based on the additional findings of two classical osteomas in the left radius and ulna and a cold non-malignant nodule of the thyroid gland. Intestinal polyposis was lacking at the time of examination. Major deletions but not microdeletions were excluded by a cytogenetic analysis with 650 chromosomal bands per haploid set. Systematic sequencing of the entire coding region of the APC gene (> 8500 bp) of the patient and five healthy controls was also performed. As a results, new APC gene polymorphisms were identified in exons 13 [A545A (A/G)] and 15 [G1678G (A/G), S1756S (G/T), P1960P (A/G)]. We also detected D1822V (A/T) which has recently been reported to be potentially related to colorectal carcinoma, and genotyped 194 randomly chosen healthy individuals from the Glasgow area for this as well as for the above variants in exons 13 and 15. Interestingly, of the 194 controls, 112 carried the DD (57.7%), 71 the DV (36.6%), and the remaining 11 (5.7%), including our patient, the VV genotype. It is therefore unlikely that APC D1822V serves as an important marker for colorectal carcinoma. In conclusion, we failed to identify obvious germline candidate mutations in > 8500 bp of the coding region of the APC gene in a patient with multiple epidermal cysts, osteomas and a thyroid gland nodule; major chromosomal deletions were excluded. Therefore, we assume that only the presence of intestinal polyposis is a marker for Gardner syndrome.     

痣样基底细胞癌综合征一家系PTCH1基因突变分析

目的 对痣样基底细胞癌综合征一家系进行PTCH1基因突变分析。 方法 提取先证者（Ⅱ5）及Ⅱ1、Ⅱ3、Ⅲ4的DNA,以50例健康人为对照。应用聚合酶链反应（PCR）、DNA直接测序明确突变位点,根据突变位点设计特异性引物,用PCR来检测突变位点从而进一步确定该家系的致病原因。 结果 先证者PTCH1基因的1条等位基因第14号外显子上2137位胞嘧啶C被胸腺嘧啶T替代（c.2137C > T）,即CAG→TAG,导致终止密码产生（Q714X）,Ⅲ4也检测到相同突变。健康对照者中未检出该突变。 结论 PTCH1基因的无义突变（c.2137C > T）可能是引起该患者临床症状的特异性突变。