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。     

Microphthalmia and linear skin defects syndrome: Precise diagnosis guides prognosis

Microphthalmia and linear skin defects syndrome (MLS) is a rare X-linked dominant disorder characterized by microphthalmia and linear atrophic plaques of the face and neck. The diagnosis of MLS can be challenging secondary to both its rarity and to clinical overlap with Goltz syndrome. Whereas the skin lesions of MLS are more likely to improve in appearance with age, the lesions of Goltz are typically persistent.     

LEOPARD综合征一家系PTPN11基因突变分析

【摘要】 目的 明确1个LEOPARD综合征家系的PTPN11基因突变。方法 对中国科学院大学宁波华美医院确诊的1例LEOPARD综合征先证者的家系进行现场调查。提取家系内4例患者、2例健康成员及与该家系无关的100例健康对照外周血标本。PCR扩增PTPN11基因所有外显子,使用Sanger测序法进行突变位点分析。结果 该家系3代14人,其中6人患病（男3例,女3例）,符合常染色体显性遗传。患者皮损主要分布于面部、躯干和四肢,具有特殊面容及心血管系统异常。4例患者存在PTPN11基因的错义突变c.1632G＞T（p.R558L）,导致第558位由精氨酸变为亮氨酸,该突变既往未曾报道。该家系2例健康成员及100例健康对照未发现PTPN11基因突变。结论 该LEOPARD综合征家系患者PTPN11基因13号外显子发生c.1632G＞T错义突变,可能是该家系患者发病的分子基础。     

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。     

Acquired cutis laxa secondary to Sweet syndrome in a child (Marshall syndrome): A rare case report

Sweet syndrome is rare in the pediatric population and usually responds well to treatment, resolving without sequelae. Marshall syndrome is a rare pediatric skin disease characterized by loss of elastic tissue (cutis laxa) secondary to acquired, localized neutrophilic dermatitis without any internal organ involvement. Only few cases of Marshall syndrome (acquired cutis laxa type II) have been reported. Systemic steroids and dapsone show excellent results in Sweet syndrome. Although there is no satisfactory treatment for cutis laxa, dapsone can be used in the acute phase for control of swelling.     

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.     

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.     

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.     

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。     

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.