Xeroderma pigmentosum – Fakten und Perspektiven

Lehmann, Janin; Seebode, Christina; Martens, Marie Christine; Emmert, Steffen

doi:10.1055/s-0043-123031

Cited by 24 publications

(29 citation statements)

References 22 publications

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“…Other genetic diseases can predispose patients to the formation of BC: XP due to germline mutations in DNA repair genes (24), which predispose to multiple skin tumours, including BCC, but also melanoma and squamous cell carcinoma (SCC), at an early age, as well as the Bazex-Dupre-Christol syndrome, and dominant X-linked cancer-prone genodermatosis, in which recent studies have reported mutations in the ACTRT1 gene and its enhancer, leading to activation of the Hh pathway in certain families (25).…”

Section: Bcc Secondary Drivers Have Been Found In Cancer Genes Suchmentioning

confidence: 99%

Update in the Management of Basal Cell Carcinoma

Basset-Séguin¹,

Herms²

2020

Acta Derm Venereol

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Basal cell carcinoma is the most frequent cancer in fairskinned adults. The molecular background to these tumours includes activation of a cellular pathway called the "sonic hedgehog pathway". Basal cell carcinomas are induced by ultraviolet light and occur more frequently on areas of skin that are exposed to the sun. Basal cell carcinomas rarely spread to other sites in the body, al though there is a risk that they will recur. There are different subtypes of these tumours with different potential to relapse. This paper gives an update of what is known about basal cell carcinomas and their treatment. The standard treatment is surgery. The prognosis for advanced basal cell carcinomas that cannot be operated on has improved with the development of systemic drugs targeting the hedgehog pathway. Basal cell carcinomas are the most frequent skin cancers in the fair-skinned adult population over 50 years of age. Their incidence is increasing throughout the world. Ultraviolet (UV) exposure is the major carcinogenic factor. Some genodermatosis can predispose to formation of basal cell carcinomas at an earlier age. Basal cell carcinomas are heterogeneous, from superficial or nodular lesions of good prognosis to very extensive difficult-to-treat lesions that must be discussed in multidisciplinary committees. Recent guidelines have updated the management of basal cell carcinoma. The prognosis is linked to the risk of recurrence of basal cell carcinoma or its local destructive capacity. Characteristic molecular events in these tumours are: (i) activation of the hedgehog pathway, which has allowed the development of hedgehog inhibitors for difficult-to-treat lesions that are not accessible to surgery or radiotherapy; (ii) high mutational burden, which suggests that hedgehog inhibitor refractory tumours could be offered immunotherapy; some trials are ongoing. The standard treatment for most basal cell carcinomas is surgery, as it allows excision margin control and shows a low risk of recurrence. Superficial lesions can be treated by non-surgical methods with significant efficacy.

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Section: Bcc Secondary Drivers Have Been Found In Cancer Genes Suchmentioning

confidence: 99%

Update in the Management of Basal Cell Carcinoma

Basset-Séguin¹,

Herms²

2020

Acta Derm Venereol

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“…About 60% of the patients present with increased sun sensitivity such as dermatitis solaris in the first weeks of life, whereas early hyperpigmentation in sun‐exposed areas is typically observed in nearly all patients. Further phenotypic features include premature aging of the skin, poikiloderma, ocular changes as well as basal cell and squamous epithelial cell carcinoma and cutaneous melanoma within the first decade of life 159,160 . Additional neurological symptoms can be observed in about 25% of the patients including diminished or absent tendon reflexes, progressive sensorineural hearing loss, speech and gait disturbances, acquired microcephaly, and cognitive impairment 160,161 .…”

Section: Pathogenesis and Clinical Phenotypes Of Selected Premature Amentioning

confidence: 99%

Premature aging disorders: A clinical and genetic compendium

2020

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Progeroid disorders make up a heterogeneous group of very rare hereditary diseases characterized by clinical signs that often mimic physiological aging in a premature manner. Apart from Hutchinson-Gilford progeria syndrome, one of the bestinvestigated progeroid disorders, a wide spectrum of other premature aging phenotypes exist, which differ significantly in their clinical presentation and molecular pathogenesis. Next-generation sequencing (NGS)-based approaches have made it feasible to determine the molecular diagnosis in the early stages of a disease. Nevertheless, a broad clinical knowledge on these disorders and their associated symptoms is still fundamental for a comprehensive patient management and for the interpretation of variants of unknown significance from NGS data sets. This review provides a detailed overview on characteristic clinical features and underlying molecular genetics of well-known as well as only recently identified premature aging disorders and also highlights novel findings towards future therapeutic options. K E Y W O R D S characteristic clinical features, hereditary, premature aging, progeroid disorders 1 | INTRODUCTION Aging is a general biological phenomenon that affects all human beings and results in a functional decline of physiological systems accompanied by an increased risk for chronic ailments with advancing chronological age. 1,2 At the molecular level, aging is for example associated with genomic instability, loss of heterochromatin, and the accumulation of macromolecular damage leading to reduced (stem) cell function and tissue regeneration. 3 Progeroid disorders show many clinical features of aging-associated pathologies and signs similar to physiological aging; however, they occur at earlier ages and often progress rapidly. In many aspects progeria therefore represents a timelapse form of aging. Premature aging processes are mostly segmental in that they involve one or more organs, but do not exhibit all aspects associated with physiological aging. Premature aging signs include, among others, alopecia, hair graying, lipodystrophy, osteoporosis, joint contractures, cataract, hearing loss, atherosclerosis, cardiovascular diseases, diabetes mellitus and malignancies at an early age. In addition to these typical aging phenotypes, progeria patients may also present with growth retardation, developmental delay, and intellectual disability. A more modular view of segmental premature aging syndromes hypothesizes that a cluster of symptoms appearing in several disorders might be due to a common underlying cause-for example, alopecia, osteoporosis and nail atrophy have been proposed to be related to telomere shortening. 4 Research into premature aging disorders aims at understanding the pathogenesis and to develop novel treatment strategies, but also intends to unshadow physiological aging processes since premature aging phenotypes mirror many of the clinical aspects of physiological aging. 3 One of the best-known premature aging disorders is the Hutchinson-Gilford progeria syndr...

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“…Severe sunburn on minimal sun exposure is a conspicuous symptom for the diagnosis of XP, but only approximately 60% of all patients show this manifestation [5]. XP is primarily diagnosed in the clinic and confirmed by functional cell-based systems as well as genetic tests.…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel DDB2 mutation in a Chinese Han family with Xeroderma pigmentosum group E:a case report and literature review

et al. 2020

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Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive genodermatosis. There are eight complementation groups of XP (XP-A to G and a variant form). XP-E is one of the least common forms, and XP-E patients are generally not diagnosed until they are adults due to a later onset of skin alterations. Case presentation: We report a case of a 28-year-old Chinese woman with freckle-like hyperpigmented macules in a sun-exposed area who is prone to develop basal cell carcinomas. A genetic study revealed a novel homozygous c.111_112del deletion in exon 1 of the DDB2 gene. Western blotting analysis revealed that the patient lacked the expression of the wild-type mature DDB2 protein. The proband was first diagnosed with XPE on the basis of clinical findings and genetic testing. Sun protection was recommended, and the patient did not develop any skin cancers during the one-year follow-up. Conclusions: We identified a novel homozygous deletion in DDB2 gene in Chinese XP-E patients having unique clinical features.

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Xeroderma pigmentosum – Fakten und Perspektiven

Cited by 24 publications

References 22 publications

Update in the Management of Basal Cell Carcinoma

Update in the Management of Basal Cell Carcinoma

Premature aging disorders: A clinical and genetic compendium

Identification of a novel DDB2 mutation in a Chinese Han family with Xeroderma pigmentosum group E:a case report and literature review

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