RESUMO
So far, confusion exists regarding the question of whether hereditary perifollicular fibromas and fibrofolliculomas can be distinguished from each other. Here, histopathological arguments are presented to clarify this terminological problem. In 1977, Birt et al. described a large kindred affected with hereditary multiple "fibrofolliculomas," which they thought were "a hitherto unrecognized pilar hamartoma," but they never claimed the fibrofolliculomas were part of a syndrome. A careful microscopic comparison shows, however, that the tumors are clinically and histopathologically identical to perifollicular fibromas, as first described by Burnier and Rejsek in 1925. Their familial occurrence was discovered in 1971 by Civatte and Le Tréguilly. Before 1977, the term "perifollicular fibroma" was used for these skin tumors. By contrast, Hornstein and Knickenberg described in 1975 perifollicular fibromas as a cutaneous marker of a syndrome characterized by a predisposition to colon cancer and pneumothorax. Later, two French groups erroneously proposed the term "Birt-Hogg-Dubé syndrome" to describe the co-occurrence of fibrofolliculomas, trichodiscomas, and acrochordons, which was contrary to what Birt et al. had in mind. Hence, today, we should discriminate between the hereditary nonsyndromic perifollicular fibromas, as documented by Civatte and Le Tréguilly and later by Birt et al., and the syndromic perifollicular fibromas, as delineated by Hornstein and Knickenberg.
Assuntos
Fibroma , Doenças do Cabelo , Hamartoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Fibroma/patologia , Hamartoma/patologia , SíndromeRESUMO
Incontinentia pigmenti (IP) is a rare X-linked dominant, male-lethal disorder characterized by pathognomic skin lesions. As described in the literature the typical cutaneous changes follow the pattern of Blaschko's lines and develop in four stages that usually start at birth. Stage 1 is called vesicular, bullous or inflammatory. The vesicles are rapidly filled with eosinophils and thus turn into pustules. Thus, the term "pustular" is relevant to the first phase of IP, and the stage can be considered as "vesiculopustular/inflammatory" to be more precise than "vesicular" or "bullous."
Assuntos
Incontinência Pigmentar , Recém-Nascido , Humanos , Masculino , Incontinência Pigmentar/diagnóstico , Incontinência Pigmentar/patologia , Pele/patologia , Vesícula/patologia , Eosinófilos/patologia , Doenças Raras/patologiaRESUMO
In autosomal dominant skin disorders, pronounced mosaic involvement may sometimes occur in the neonate, originating in a heterozygous embryo from early loss of heterozygosity, probably during the first week after fertilization. In biallelic phenotypes, such overlaying mosaic involvement may coexist with disseminated mosaicism, for example, in neurofibromatosis or tuberous sclerosis. In other phenotypes, however, classical nonsegmental involvement tends to appear much later, which is why the superimposed mosaic is a heralding feature. In Brooke-Spiegler syndrome (eccrine cylindromatosis), a large pedigree documented a 5-year-old boy with multiple, congenital small eccrine cylindromas along the lines of Blaschko. Disseminated cylindromas were absent because they usually appear in adulthood. ̶ In Hornstein-Knickenberg syndrome, an affected woman had an 8-year-old son with a nevus comedonicus-like lesion exemplifying a forerunner of the syndrome. ("Birt-Hogg-Dubé syndrome" represents a nonsyndromic type of hereditary perifollicular fibromas.) In glomangiomatosis, neonatal superimposed mosaicism is a heralding feature because disseminated lesions appear during puberty or adulthood. Linear porokeratosis is a harbinger of disseminated porokeratosis that develops 30 or 40 years later. ̶ Cases of superimposed linear Darier disease were forerunners of nonsegmental manifestation. ̶ In a case of Hailey-Hailey disease, neonatal mosaic lesions heralded nonsegmental involvement that began 22 years later.
Assuntos
Carcinoma Adenoide Cístico , Humanos , Criança , Mosaicismo , Padrões de Herança , FenótipoRESUMO
Autosomal dominant, sex-limited inheritance is a distinct mode of transmission that should not be conflated with X-linked inheritance. From animal studies, we know that sex-limited inheritance implies the chance to "turn off" some genes in either males or females, in order to meliorate the phenotype, for example, by improving the fecundity. In this way, sex-limited genes play an important role in the evolution of diverse species of animals. In human genetics, however, the biological significance of sex-limited genes is unknown until today. When screening the literature, we found, thus far, three human examples of sex-limited transmission. Autosomal dominant, male-limited inheritance has meticulously been studied in a particular form of precocious puberty. Limitation to females was described in autosomal dominant lymphedema of the CESLR1 type, being underpinned by convincing molecular findings. Another example is white lentiginosis of Grosshans that shows clinical evidence of such mode of transmission although molecular findings are lacking as yet. In the animal kingdom, autosomal dominant sex-limited inheritance is a well-established phenomenon that has extensively been studied in various species such as butterflies, damselflies, fish (cichlids), and birds. Hence, at this point in time, it seems likely that other human examples of this mode of inheritance have previously been reported or will be published in the future.
Assuntos
Borboletas , Feminino , Animais , Humanos , Masculino , Padrões de Herança , Fenótipo , Fatores Sexuais , Genes Dominantes , LinhagemRESUMO
Sarcoidosis is a chronic granulomatous disorder affecting the lungs, skin, and many other organs. Twin studies suggest that genetic factors account, to a large degree, for the etiology of the disorder. Hence, theoretically, we could postulate that the phenomenon of superimposed mosaicism in the form of a pronounced segmental involvement, overlaying the disseminated non-segmental lesions, should also occur in sarcoidosis. Indeed, one case suggesting superimposed mosaicism in cutaneous sarcoidosis was found in the literature and is reassessed here.
Assuntos
Sarcoidose , Dermatopatias Genéticas , Dermatopatias , Humanos , Mosaicismo , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Dermatopatias Genéticas/patologia , Pele/patologia , Sarcoidose/diagnóstico , Sarcoidose/genética , Dermatopatias/diagnóstico , Dermatopatias/genética , Dermatopatias/patologiaRESUMO
Phacomatosis pigmentokeratotica (PPK) is defined by the association of papular nevus spilus arranged in a flag-like pattern and sebaceous nevus following Blaschko's lines. A systematic search of the worldwide literature retrieved 95 well-established PPK cases. An additional 30 cases were excluded for a number of reasons. Based on this study, we propose to rename PPK phacomatosis spilosebacea (PSS). Mosaic mutations of the HRAS gene are the only proven cause of PSS. The extracutaneous abnormalities of PSS result from various degrees of intermingling of Schimmelpenning syndrome and papular nevus spilus syndrome. PSS seems to be a condition at particularly high risk of developing basal cell carcinoma, urogenital malignancies, and vitamin D-resistant hypophosphatemic rickets. Extracutaneous abnormalities were detected in approximately 75% of PSS cases.
Assuntos
Carcinoma Basocelular , Lentigo , Síndromes Neurocutâneas , Nevo Pigmentado , Neoplasias Cutâneas , Esclerose Tuberosa , Humanos , Síndromes Neurocutâneas/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Nevo Pigmentado/genética , Nevo Pigmentado/patologia , Carcinoma Basocelular/patologiaRESUMO
Plexiform neurofibromas occurring in approximately 20-50% of all neurofibromatosis type-1 (NF1) cases are histologically benign tumors, but they can be fatal due to compression of vital structures or transformation to malignant sarcomas or malignant peripheral nerve sheath tumors. All sizeable plexiform neurofibromas are thought to result from an early second mutation giving rise to a loss of heterozygosity of the NF1 gene. In this unusual case, a 12-year-old girl presented with a rapidly growing, extremely extensive plexiform neurofibroma with segmental distribution over the entire right arm, extending to the right chest wall and mediastinum, superimposed on classic cutaneous lesions of NF1. After several surgical interventions, the patient was efficiently treated with an oral selective MEK inhibitor, selumetinib, which resulted in a rapid reduction of the tumor volume. Molecular analysis of the NF1 gene revealed a c.2326-2 A>G splice-site mutation in the clinically unaffected skin, peripheral blood sample, and plexiform neurofibroma, which explains the general clinical symptoms. Furthermore, a novel likely pathogenic variant, c.4933dupC (p.Leu1645Profs*7), has been identified exclusively in the girl's plexiform neurofibromas. This second-hit mutation can explain the extremely extensive segmental involvement.
Assuntos
Neurofibroma Plexiforme , Neurofibromatose 1 , Feminino , Humanos , Criança , Neurofibroma Plexiforme/genética , Genes da Neurofibromatose 1 , Mosaicismo , Neurofibromatose 1/genética , MutaçãoRESUMO
Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho-genetic mechanism for the development of the lesions. However, the molecular mechanism leading to development of porokeratosis plantaris, palmaris et disseminata is not known. This study analysed a cohort of 4 patients with linear porokeratosis and 3 patients with porokeratosis plantaris, palmaris et disseminata, and performed mutation analyses of DNA extracted from blood samples and skin biopsies. All of the study patients carried the heterozygous germline variant c.70+5G>A in the MVD gene. Loss of heterozygosity due to a second hit mutation was found in affected skin of 3 patients with linear porokeratosis and 2 patients with porokeratosis plantaris, palmaris et disseminata. These results suggest that porokeratosis plantaris, palmaris et disseminata shares the same pathogenetic mechanism as other porokeratosis subtypes and belongs to the phenotypic spectrum of MVD-associated porokeratosis.
Assuntos
Poroceratose , Análise Mutacional de DNA , Genitália , Humanos , Mutação , Poroceratose/diagnóstico , Poroceratose/genética , PeleRESUMO
A 4-year-old girl presented with congenital patches of scalp alopecia, which on physical examination, was consistent with blaschkolinear alopecic patches with mild epidermal atrophy. Similar atrophic hypopigmented patches were seen on the trunk and proximal extremities. With the clinical suspicion of Conradi-Hünermann-Happle syndrome, genetic testing was performed and revealed a mutation in the EBP gene. Despite characteristic cutaneous findings, no skeletal, ocular, or other anomalies were found on further evaluation.
Assuntos
Condrodisplasia Punctata , Anormalidades da Pele , Alopecia , Pré-Escolar , Condrodisplasia Punctata/diagnóstico , Condrodisplasia Punctata/genética , Olho , Face , Feminino , HumanosRESUMO
Mosaicism denotes an individual who has at least two populations of cells with distinct genotypes that are derived from a single fertilized egg. Genetic variation among the cell lines can involve whole chromosomes, structural or copy-number variants, small or single-nucleotide variants, or epigenetic variants. The mutational events that underlie mosaic variants occur during mitotic cell divisions after fertilization and zygote formation. The initiating mutational event can occur in any types of cell at any time in development, leading to enormous variation in the distribution and phenotypic effect of mosaicism. A number of classification proposals have been put forward to classify genetic mosaicism into categories based on the location, pattern, and mechanisms of the disease. We here propose a new classification of genetic mosaicism that considers the affected tissue, the pattern and distribution of the mosaicism, the pathogenicity of the variant, the direction of the change (benign to pathogenic vs. pathogenic to benign), and the postzygotic mutational mechanism. The accurate and comprehensive categorization and subtyping of mosaicisms is important and has potential clinical utility to define the natural history of these disorders, tailor follow-up frequency and interventions, estimate recurrence risks, and guide therapeutic decisions.
Assuntos
Variações do Número de Cópias de DNA , Mosaicismo , Análise Mutacional de DNA , Humanos , Mutação , SoftwareRESUMO
In 1945, the Journal of Heredity published an impressive article entitled "A human mosaic: bilaterally asymmetrical noevus pigmentosus pilosus et mollusciformis unilateralis." The author was M. Zlotnikoff, a Russian physician working in Ivanovo, a city located approximately 250 km northeast of Moscow. Zlotnikoff described a 24-year-old woman with a congenital linear epidermal naevus in a systematized and strictly unilateral arrangement. For the first time, the author explained this disorder as a mosaic resulting from a somatic mutation that occurred at an early stage of embryonic development. However, because this article was published immediately after the war, it fell into oblivion, despite the fact that it was of utmost importance in clinical dermatology. Zlotnikoff's work is all the more remarkable as the author had never heard of the lines of Blaschko.
Assuntos
Mosaicismo , Nevo/história , Dermatopatias Genéticas/história , Feminino , História do Século XX , Humanos , Mutação , Nevo/genética , Federação Russa , Dermatopatias Genéticas/genéticaRESUMO
is missing (Quiz).
Assuntos
Ceratodermia Palmar e Plantar/genética , Biópsia , Diagnóstico Diferencial , Feminino , Predisposição Genética para Doença , Humanos , Queratina-1/genética , Pessoa de Meia-Idade , MutaçãoRESUMO
The"Bork-Baykal phenomenon" refers to the sparing of the nipple-areola complex in large congenital melanocytic nevi involving the breast. So far, this finding has not been reported in vascular anomalies. We present four patients with an extensive capillary malformation (CM) involving the breast that was found to exhibit a similar sparing of the nipple and areola. All of these capillary nevi were associated with asymmetric overgrowth.
Assuntos
Capilares/anormalidades , Classe I de Fosfatidilinositol 3-Quinases/genética , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Malformações Vasculares/diagnóstico , Malformações Vasculares/genética , Adolescente , Criança , Diagnóstico Diferencial , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Nevo Pigmentado/genética , Nevo Pigmentado/fisiopatologia , Mamilos , Estudos de Amostragem , Índice de Gravidade de Doença , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/fisiopatologiaRESUMO
BACKGROUND: In many complex genetic syndromes, various distinct capillary nevi may serve as diagnostic clues. OBJECTIVE: To render dermatologists in practice capable of recognizing and classifying such cutaneous markers. MATERIAL AND METHODS: On the basis of the literature and own observations, this review describes 14 different syndromes associated with capillary nevi that can be recognized by dermatologists as a diagnostic indication. RESULTS: The following capillary nevi can be distinguished for syndrome recognition: nevus flammeus of the Sturge-Weber syndrome (GNAQ), port-wine nevus of the Proteus type (AKT1), port-wine nevus of the PIK3CA-related overgrowth spectrum (PROS) type, midfacial port-wine patch of the PROS type, reticulate capillary nevus heralding megalencephaly-capillary nevus syndrome that is likewise part of PROS, cutis marmorata telangiectatica congenita (van Lohuizen syndrome), nevus roseus, nevus vascularis mixtus, rhodoid nevus (RASA1), nevus anemicus as a diagnostic indication of neurofibromatosis 1 and Carter-Mirzaa macules (STAMBP). CONCLUSION: A diagnostic difficulty lies in the fact that not all syndromes associated with capillary nevi have been elucidated at the molecular level. For this reason, the preliminary dimension of the present review should be borne in mind. On the other hand, dermatologists in practice now have the fascinating chance to stimulate further advances in this particular field of knowledge by asking experts in dermatology, pediatrics or medical genetics how to solve the problem of molecular syndrome recognition in a puzzling case.
Assuntos
Mancha Vinho do Porto , Anormalidades da Pele , Dermatopatias Vasculares , Criança , Humanos , Pele , SíndromeAssuntos
Dermatologia , História do Século XX , Dermatologia/história , História do Século XXI , Alemanha , HumanosRESUMO
A female infant presented with an ulcerated lesion on the right side of the vulva. Histopathology showed a suprabasal acantholytic blister with intact papillae protruding into the blister cavity and a few dyskeratotic cells. There were no signs of injury on other locations. Family history was unremarkable. Our patient may have linear Hailey-Hailey disease of the vulva, most likely a case of type 1 mosaic.
Assuntos
Pênfigo Familiar Benigno/diagnóstico , Doenças da Vulva/patologia , Acantólise/patologia , Feminino , Humanos , Lactente , Mosaicismo , Vulva/patologiaRESUMO
Terminal osseous dysplasia is a rare, X-linked syndrome, presumptively embryonic lethal in males, which has recently been described with highly characteristic skin findings. The presence of intracytoplasmic inclusion bodies in fibroblasts has been considered an exclusive finding of infantile digital fibromatosis. This is the first report documenting digital fibromas with intracytoplasmic inclusion bodies in a classic case of terminal osseous dysplasia.
Assuntos
Fibroma/patologia , Dedos/anormalidades , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Deformidades Congênitas dos Membros/diagnóstico , Osteocondrodisplasias/diagnóstico , Transtornos da Pigmentação/diagnóstico , Dedos do Pé/anormalidades , Pré-Escolar , Feminino , Pé/patologia , Mãos/patologia , Humanos , Corpos de Inclusão/patologia , Pele/patologiaRESUMO
Superimposed linear atopic dermatitis is rarely manifested in polygenic disease as a counterpart to type 2 segmental mosaicism of monogenic skin diseases. Linear arrangement following Blaschko lines represents more severe disease on a generalized background of atopic dermatitis, perhaps reflecting clonal loss of heterozygosity. Only three cases of superimposed linear atopic dermatitis have been reported; we describe three additional cases.