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1.
Dermatol Clin ; 37(2): 229-239, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30850045

RESUMO

The discoveries of new genes underlying genetic skin diseases have occurred at a rapid pace, supported by advances in DNA sequencing technologies. These discoveries have translated to an improved understanding of disease mechanisms at a molecular level and identified new therapeutic options based on molecular targets. This article highlights just a few of these recent discoveries for a diverse group of skin diseases, including tuberous sclerosis complex, ichthyoses, overgrowth syndromes, interferonopathies, and basal cell nevus syndrome, and how this has translated into novel targeted therapies and improved patient care.


Assuntos
Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/terapia , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/genética , Doenças Autoimunes do Sistema Nervoso/terapia , Síndrome do Nevo Basocelular/diagnóstico , Síndrome do Nevo Basocelular/genética , Síndrome do Nevo Basocelular/terapia , Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Dermabrasão , Fármacos Dermatológicos/uso terapêutico , Testes Genéticos , Doenças Hereditárias Autoinflamatórias/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/terapia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Eritrodermia Ictiosiforme Congênita/diagnóstico , Eritrodermia Ictiosiforme Congênita/genética , Eritrodermia Ictiosiforme Congênita/terapia , Inibidores de Janus Quinases/uso terapêutico , Terapia a Laser , Lipoma/diagnóstico , Lipoma/genética , Lipoma/terapia , Técnicas de Diagnóstico Molecular , Mosaicismo , Anormalidades Musculoesqueléticas/diagnóstico , Anormalidades Musculoesqueléticas/genética , Anormalidades Musculoesqueléticas/terapia , Malformações do Sistema Nervoso/diagnóstico , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/terapia , Nevo/diagnóstico , Nevo/genética , Nevo/terapia , Pitiríase Rubra Pilar/diagnóstico , Pitiríase Rubra Pilar/genética , Pitiríase Rubra Pilar/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Síndrome de Proteu/diagnóstico , Síndrome de Proteu/genética , Síndrome de Proteu/terapia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Análise de Sequência de DNA , Dermatopatias Genéticas/genética , Protetores Solares/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/genética , Esclerose Tuberosa/terapia , Ustekinumab/uso terapêutico
2.
Pediatr Dermatol ; 36(1): e20-e22, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30548334

RESUMO

Dermatophyte infections are exceedingly rare in neonates, possibly due to the thin stratum corneum and high sebum content of neonatal skin. Only a handful of cases of tinea faciei have been reported in neonates, with the majority of reports occuring in India. Here, we report what to our knowledge is the earliest reported presentation of tinea faciei in the United States. We also provide a brief literature review of other reported cases of tinea faciei in neonates less than 30 days of age.


Assuntos
Dermatoses Faciais/diagnóstico , Tinha/diagnóstico , Antifúngicos/uso terapêutico , Diagnóstico Diferencial , Face/microbiologia , Dermatoses Faciais/tratamento farmacológico , Dermatoses Faciais/microbiologia , Feminino , Humanos , Recém-Nascido , Pele/microbiologia , Tinha/tratamento farmacológico , Trichophyton/isolamento & purificação
3.
J Am Acad Dermatol ; 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30287322

RESUMO

BACKGROUND: Infant death in KID syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood. OBJECTIVE: To discover characteristics that account for poor outcomes in lethal KID syndrome. METHODS: We collected four new cases and nine previously reported, genotyped cases of lethal KID syndrome. We performed new molecular modeling of the lethal mutants GJB2 p.A88V and GJB2 p.G45E. RESULTS: Infant death occurred in all patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations. Early death with those two "lethal" mutations is likely multifactorial: during life all had at least one serious infection; most had poor weight gain and severe respiratory difficulties; many had additional anatomic abnormalities. Structural modeling of GJB2 p.G45E identified no impact on the salt bridge previously predicted to account for abnormal central CO2 sensing of GJB2 p.A88V. LIMITATIONS: Clinical review was retrospective. CONCLUSION: GJB2 p.G45E and p.A88V are the only KID syndrome mutations associated with uniform early lethality. Those electro-physiologically severe mutations in GJB2 reveal abnormalities in many organs in lethal KID syndrome. All KID syndrome patients may have subtle abnormalities beyond eyes, ears and skin. Early genotyping of KID syndrome births will inform prognostic discussion.

4.
Pediatr Dermatol ; 35(6): 859-863, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30168195

RESUMO

When lichen planus involves the scalp, it is known as lichen planopilaris, and when it involves the eye, it is known as ocular lichen planus; both are rare. Early detection and targeted therapy are crucial in preventing hair loss and scarring conjunctivitis. Little is known regarding appropriate treatment for lichen planopilaris. The objective of this case study is to present a new case of pediatric ocular lichen planus and lichen planopilaris and to identify all reported cases of pediatric lichen planopilaris, highlighting disease involvement, treatment, and response to treatment.


Assuntos
Líquen Plano/diagnóstico , Dermatoses do Couro Cabeludo/diagnóstico , Criança , Ciclosporina/uso terapêutico , Olho/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Líquen Plano/tratamento farmacológico , Metotrexato/uso terapêutico , Prednisolona/uso terapêutico , Couro Cabeludo/patologia , Dermatoses do Couro Cabeludo/tratamento farmacológico
5.
Artigo em Inglês | MEDLINE | ID: mdl-30170123

RESUMO

BACKGROUND: Caspase activation and recruitment domain 11 (CARD11) encodes a scaffold protein in lymphocytes that links antigen receptor engagement with downstream signaling to nuclear factor κB, c-Jun N-terminal kinase, and mechanistic target of rapamycin complex 1. Germline CARD11 mutations cause several distinct primary immune disorders in human subjects, including severe combined immune deficiency (biallelic null mutations), B-cell expansion with nuclear factor κB and T-cell anergy (heterozygous, gain-of-function mutations), and severe atopic disease (loss-of-function, heterozygous, dominant interfering mutations), which has focused attention on CARD11 mutations discovered by using whole-exome sequencing. OBJECTIVES: We sought to determine the molecular actions of an extended allelic series of CARD11 and to characterize the expanding range of clinical phenotypes associated with heterozygous CARD11 loss-of-function alleles. METHODS: Cell transfections and primary T-cell assays were used to evaluate signaling and function of CARD11 variants. RESULTS: Here we report on an expanded cohort of patients harboring novel heterozygous CARD11 mutations that extend beyond atopy to include other immunologic phenotypes not previously associated with CARD11 mutations. In addition to (and sometimes excluding) severe atopy, heterozygous missense and indel mutations in CARD11 presented with immunologic phenotypes similar to those observed in signal transducer and activator of transcription 3 loss of function, dedicator of cytokinesis 8 deficiency, common variable immunodeficiency, neutropenia, and immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome. Pathogenic variants exhibited dominant negative activity and were largely confined to the CARD or coiled-coil domains of the CARD11 protein. CONCLUSION: These results illuminate a broader phenotypic spectrum associated with CARD11 mutations in human subjects and underscore the need for functional studies to demonstrate that rare gene variants encountered in expected and unexpected phenotypes must nonetheless be validated for pathogenic activity.

6.
7.
Orphanet J Rare Dis ; 13(1): 31, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29415745

RESUMO

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by a predisposition to develop multiple benign tumors. A major feature of NF1 is the development of localized cutaneous neurofibromas. Cutaneous neurofibromas manifest in > 99% of adults with NF1 and are responsible for major negative effects on quality of life. Previous reports have correlated increased burden of cutaneous neurofibromas with age and pregnancy, but longitudinal data are not available to establish a quantitative natural history of these lesions. The purpose of this study is to conduct a prospective natural history study of 22 adults with NF1 over an 8-year period to quantify cutaneous neurofibroma number and size. RESULTS: The average monthly increase in volume for cutaneous neurofibromas was 0.37 mm3 in the back region (95% CI (0.23, 0.51), p < 0.0001), 0.28 mm3 in the abdominal region (95% CI (0.16, 0.41), p < 0.0001), and 0.21 mm3 in the arm/leg region (95% CI (0.08, 0.34), p = 0.0022). The number of cutaneous neurofibromas significantly increased in the back (slope = 0.032, p = 0.011) and abdominal (slope = 0.018, p = 0.026) regions, while the leg/arm regions retained a positive trend (slope = 0.004, p = 0.055). CONCLUSIONS: The number and volume of cutaneous neurofibromas significantly increased over an 8-year timespan; however, the rate of increase is variable by individual and body region. These findings may provide insight into cutaneous neurofibroma development and benefit researchers considering clinical trials targeting cutaneous neurofibromas.

8.
JAMA Dermatol ; 153(6): 537-543, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28403434

RESUMO

Importance: Bathing suit ichthyosis (BSI) is a rare congenital disorder of keratinization characterized by restriction of scale to sites of relatively higher temperature such as the trunk, with cooler areas remaining unaffected. Fewer than 40 cases have been reported in the literature. Bathing suit ichthyosis is caused by recessive, temperature-sensitive mutations in the transglutaminase-1 gene (TGM1). Clear genotype-phenotype correlations have been difficult to establish because several of the same TGM1 mutations have been reported in BSI and other forms of congenital ichthyosis. We identify novel and recurrent mutations in 16 participants with BSI. Objective: To expand the genotypic spectrum of BSI, identifying novel TGM1 mutations in patients with BSI, and to use BSI genotypes to draw inferences about the temperature sensitivity of TGM1 mutations. Design, Setting, and Participants: A total of 16 participants with BSI from 13 kindreds were identified from 6 academic medical centers. A detailed clinical history was obtained from each participant, including phenotypic presentation at birth and disease course. Each participant underwent targeted sequencing of TGM1. Main Outcomes and Measures: Phenotypic and genotypic characteristics in these patients from birth onward. Results: Of the 16 participants, 7 were male, and 9 were female (mean age, 12.6 years; range, 1-39 years). We found 1 novel TGM1 indel mutation (Ile469_Cys471delinsMetLeu) and 8 TGM1 missense mutations that to our knowledge have not been previously reported in BSI: 5 have been previously described in non-temperature-sensitive forms of congenital ichthyosis (Arg143Cys, Gly218Ser, Gly278Arg, Arg286Gln, and Ser358Arg), and 3 (Tyr374Cys, Phe495Leu, and Ser772Arg) are novel mutations. Three probands were homozygous for Arg264Trp, Arg286Gln, or Arg315Leu, indicating that these mutations are temperature sensitive. Seven of 10 probands with a compound heterozygous TGM1 genotype had a mutation at either arginine 307 or 315, providing evidence that mutations at these sites are temperature sensitive and highlighting the importance of these residues in the pathogenesis of BSI. Conclusions and Relevance: Our findings expand the genotypic spectrum of BSI and the understanding of temperature sensitivity of TGM1 mutations. Increased awareness of temperature-sensitive TGM1 genotypes should aid in genetic counseling and provide insights into the pathophysiology of TGM1 ichthyoses, transglutaminase-1 enzymatic activity, and potential therapeutic approaches.


Assuntos
Temperatura Corporal/genética , Ictiose Lamelar/genética , Transglutaminases/genética , Centros Médicos Acadêmicos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Mutação INDEL , Ictiose Lamelar/fisiopatologia , Lactente , Masculino , Mutação de Sentido Incorreto , Fenótipo , Adulto Jovem
9.
Dermatol Online J ; 22(11)2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28329565

RESUMO

Atypical complete DiGeorge syndrome (DGS) is an extremely rare congenital disease characterized by an eczematous dermatitis, lymphadenopathy, and an oligoclonal T-cell proliferation. Because its initial presentation may be confused with other types of eczematous dermatitis, diagnosis and treatment are usually delayed. We describe herein a case of an infant with atypical complete DGS to draw attention to the clinical and histopathological findings that lead us to the diagnosis.


Assuntos
Síndrome de DiGeorge/diagnóstico , Dermatopatias/diagnóstico , Pele/patologia , Síndrome de DiGeorge/complicações , Humanos , Lactente , Masculino , Dermatopatias/etiologia , Dermatopatias/patologia
10.
Dermatol Online J ; 21(8)2015 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-26437160

RESUMO

Bullous pemphigoid (BP) is a common autoimmune blistering disease in the adult population, but extremely rare in the pediatric population. Childhood BP usually has a favorable prognosis and responds well to topical and oral steroids. However, for patients that do not respond to corticosteroids, therapeutic alternatives are scarce. We report a case of a toddler with recalcitrant BP who was successfully treated with mycophenolate mofetil (MMF).


Assuntos
Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Penfigoide Bolhoso/tratamento farmacológico , Antibacterianos/uso terapêutico , Clindamicina/uso terapêutico , Dapsona/uso terapêutico , Diagnóstico Diferencial , Resistência a Medicamentos , Humanos , Imunossupressores/farmacologia , Lactente , Subpopulações de Linfócitos/efeitos dos fármacos , Masculino , Ácido Micofenólico/farmacologia , Ácido Micofenólico/uso terapêutico , Penfigoide Bolhoso/diagnóstico , Prednisona/uso terapêutico , Prurido/tratamento farmacológico , Indução de Remissão , Dermatopatias Vesiculobolhosas/diagnóstico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/etiologia , Superinfecção/tratamento farmacológico , Superinfecção/etiologia , Urticária/tratamento farmacológico
11.
Dermatol Surg ; 41(5): 572-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25915625

RESUMO

BACKGROUND: Margin evaluation of melanoma in situ (MIS) is difficult because of its ill-defined clinical borders. Wood's light examination is commonly used to help delineate MIS margin before excision. OBJECTIVE: To prospectively study the accuracy of preoperative Wood's light examination for margin assessment of MIS. MATERIALS AND METHODS: The authors evaluated 60 patients before excision of MIS under white light and Wood's light. Staged excision was performed using the square procedure technique. After achieving clear margins, they compared final wound size with expected wound size if surgical margins had been based on Wood's light examination. RESULTS: Seven patients (11.7%) had Wood's light enhancement beyond the visible margin of the biopsy site. In all 7, increased wounding would have occurred if the surgical margins had been based on Wood's light examination. In 1 of the 7, use of the Wood's light examination would have reduced the surgical stages needed by 1 stage but would have increased the wound size by 83.3%. CONCLUSION: Wood's light examination has limited utility if complete excisional biopsy of MIS is performed before treatment. In this study, surgical margin based on the Wood's light examination would have resulted in an increased average wound size and would not have reduced the number of stages needed when performing the square procedure.


Assuntos
Melanoma/patologia , Neoplasias Cutâneas/patologia , Raios Ultravioleta , Adulto , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Melanoma/etiologia , Melanoma/cirurgia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/cirurgia
14.
Orphanet J Rare Dis ; 9: 202, 2014 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-25475340

RESUMO

BACKGROUND: Skin neurofibromas represent one of the main clinical manifestations of neurofibromatosis 1, and their number varies greatly between individuals. Quantifying their number is an important step in the methodology of many clinical studies, but counting neurofibromas one by one in individuals with thousands of tumors is arduous, time-consuming, and subject to intra and interexaminer variability. We aimed to evaluate the efficacy of a new methodology for skin neurofibromas quantification using paper frames. METHODS: The sample comprised 92 individuals with NF1. Paper frames, with a central square measuring 100 cm2, were placed on the back, abdomen and thigh. Images were taken, transferred to a computer and two independent examiners counted the neurofibromas. The average number of neurofibromas/100 cm2 of skin was obtained from the mean of the three values. The differences in the quantity of neurofibromas counted by two examiners were evaluated with Intraclass correlation coefficient (ICC), paired t-test, Bland-Altman and survival-agreement plots. To evaluate the predictive value of the method in obtaining the total number of neurofibromas, 49 participants also had their tumors counted one by one. Reproducibility was assessed with Pearson's correlation coefficients and simple linear regression model. RESULTS: There was excellent agreement between examiners (ICC range 0.992-0.997) and the total number of skin neurofibromas could be predicted by the adhesive frames technique using a specific formula (P < 0.0001). CONCLUSIONS: In this article we describe a reliable, easy and rapid technique using paper frames to quantify skin neurofibromas that accurately predicts the total number of these tumors in patients with NF1. This method may be a useful tool in clinical practice and clinical research to help achieve an accurate quantitative phenotype of NF1.


Assuntos
Neurofibroma/diagnóstico , Neurofibromatose 1/diagnóstico , Papel , Neoplasias Cutâneas/diagnóstico , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibroma/epidemiologia , Neurofibromatose 1/epidemiologia , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Neoplasias Cutâneas/epidemiologia , Adulto Jovem
15.
Am J Dermatopathol ; 36(12): e194-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25051104

RESUMO

We present a case of a 6-year-old girl with recessive dystrophic epidermolysis bullosa (EB) who presented with a large pigmented lesion clinically concerning for melanoma. After histological examination and fluorescent in situ hybridization analysis, diagnosis of EB nevus was performed. EB nevi are benign melanocytic neoplasms with histological findings similar to recurrent nevi occurring in all types of EB. They often mimic melanoma clinically, dermatoscopically, and histopathologically. The ability to recognize an EB nevus is essential for appropriate management of the patient. Unnecessary surgical excision in patients with already high-risk EB should be avoided. Close monitoring of these lesions is recommended because no cases of transformation to melanoma have been described.


Assuntos
Epidermólise Bolhosa Distrófica/complicações , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Axila , Criança , Feminino , Humanos , Nevo Pigmentado/complicações , Neoplasias Cutâneas/complicações
16.
Pediatr Dermatol ; 31(1): e6-9, 2014 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23937359

RESUMO

Systemic polyarteritis nodosa (PAN) is a vasculitis that affects small to medium-size arteries. Onset in childhood is rare and can cause significant morbidity. Often, cutaneous manifestations can provide early clues toward diagnosis. This article describes a case of childhood systemic PAN that presented with fever, a necrotic skin lesion, and oral ulceration. Intestinal perforation complicated this case. Prompt recognition of childhood PAN is important to prevent serious complications.


Assuntos
Imunossupressores/uso terapêutico , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/tratamento farmacológico , Pré-Escolar , Colo/patologia , Diagnóstico Precoce , Humanos , Masculino , Morbidade , Poliarterite Nodosa/patologia , Pele/patologia
17.
Am J Dermatopathol ; 35(1): e16-21, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23348144

RESUMO

Proliferative (cellular) nodules (PN) which mimic malignant melanoma clinically and histologically are described in congenital melanocytic nevi (CMN) and may pose significant diagnostic challenges. We report the case of a 10-day-old male with a giant congenital nevus involving the neck, upper chest, back, and left shoulder containing several nodular lesions, some crusted. Biopsy of a nodule revealed densely packed nevus cells with hyperchromatic round to oval and occasionally irregularly shaped nuclei. There was no necrosis or pushing border, and the nodule blended with the adjacent nevus; however, the lesion demonstrated a significant number of mitoses (27 per mm2) and a 60% labeling index with Ki-67. Further analysis by fluorescence in situ hybridization (FISH) with a 4-color probe set targeting 6p25, 6q23, 11q13, and centromere 6 revealed increased chromosomal copy numbers of all 4 probes, which was interpreted as evidence of polyploidy. In addition, analysis of DNA copy number changes using a single nucleotide polymorphism microarray (Affymetrix, Santa Clara, CA) showed no chromosomal aberrations. The diagnosis of PN in a giant congenital nevus was eventually rendered. At 13-month follow-up, the nodules showed no evidence of growth. Our case illustrates that PNs in the neonatal period might demonstrate extreme mitotic activity. This feature is worrisome when encountered in melanocytic lesions; however, it should not trigger by itself a diagnosis of melanoma in the absence of other histologic criteria of malignancy. In addition, we document polyploidy by FISH in PN, which can potentially be misinterpreted as a FISH-positive result.


Assuntos
Proliferação de Células , Melanoma/patologia , Mitose , Nevo Pigmentado/patologia , Neoplasias Cutâneas/patologia , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia , Hibridização Genômica Comparativa , Variações do Número de Cópias de DNA , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Recém-Nascido , Antígeno Ki-67/análise , Masculino , Nevo Pigmentado/química , Nevo Pigmentado/congênito , Nevo Pigmentado/genética , Análise de Sequência com Séries de Oligonucleotídeos , Poliploidia , Valor Preditivo dos Testes , Neoplasias Cutâneas/química , Neoplasias Cutâneas/congênito , Neoplasias Cutâneas/genética
18.
Hum Mutat ; 34(4): 587-94, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23316014

RESUMO

Missense mutations affecting membrane-bound transcription factor protease site 2 (MBTPS2) have been associated with Ichthyosis Follicularis with Atrichia and Photophobia (IFAP) syndrome with or without BRESHECK syndrome, with keratosis follicularis spinulosa decalvans, and Olmsted syndrome. This metalloprotease activates, by intramembranous trimming in conjunction with the protease MBTPS1, regulatory factors involved in sterol control of transcription and in cellular stress response. In this study, 11 different MBTPS2 missense mutations detected in patients from 13 unrelated families were correlated with the clinical phenotype, with their effect on cellular growth in media without lipids, and their potential role for sterol control of transcription. Seven variants were novel [c.774C>G (p.I258M); c.758G>C (p.G253A); c.686T>C (p.F229S); c.1427T>C (p.L476S); c.1430A>T (p.D477V); c.1499G>A (p.G500D); c.1538T>C (p.L513P)], four had previously been reported in unrelated sibships [c.261G>A (p.M87I); c.1286G>A (p.R429H); c.1424T>C (p.F475S); c.1523A>G (p.N508S)]. In the enzyme, the mutations cluster in transmembrane domains. Amino-acid exchanges near the active site are more detrimental to functionality of the enzyme and, clinically, associated with more severe phenotypes. In male patients, a genotype-phenotype correlation begins to emerge, linking the site of the mutation in MBTPS2 with the clinical outcome described as IFAP syndrome with or without BRESHECK syndrome, keratosis follicularis spinulosa decalvans, X-linked, Olmsted syndrome, or possibly further X-linked traits with an oculocutaneous component.


Assuntos
Alopecia/genética , Estudos de Associação Genética , Ictiose/genética , Metaloendopeptidases/genética , Mutação de Sentido Incorreto , Fotofobia/genética , Adolescente , Alelos , Alopecia/diagnóstico , Animais , Linhagem Celular , Criança , Pré-Escolar , Feminino , Teste de Complementação Genética , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Ictiose/diagnóstico , Masculino , Metaloendopeptidases/química , Metaloendopeptidases/metabolismo , Repetições de Microssatélites , Fenótipo , Fotofobia/diagnóstico , Polimorfismo de Nucleotídeo Único , Transporte Proteico , Dermatopatias Genéticas/diagnóstico , Dermatopatias Genéticas/genética , Adulto Jovem
19.
Pediatr Dermatol ; 30(6): e194-7, 2013 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23316753

RESUMO

Infantile hemangiomas (IHs) are common benign tumors of childhood. IHs often regress satisfactorily without intervention, but a subset of IHs may lead to functional or cosmetic morbidity necessitating therapy. PHACE syndrome is characterized by a variety of neurocutaneous and vascular anomalies that typically include segmental hemangiomas. We present an infant with PHACE syndrome and segmental IH that failed conventional first-line therapies. Treatment with sirolimus provided benefit with regression of the cutaneous IH. As an inhibitor of the mammalian target of rapamycin (mTOR) pathway, the effective use of sirolimus may shed light on the emerging role of mTOR signaling in the development and pathogenesis of IHs.


Assuntos
Coartação Aórtica/tratamento farmacológico , Anormalidades do Olho/tratamento farmacológico , Neoplasias Faciais/tratamento farmacológico , Hemangioma/tratamento farmacológico , Síndromes Neurocutâneas/tratamento farmacológico , Sirolimo/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Antibióticos Antineoplásicos/uso terapêutico , Feminino , Humanos , Recém-Nascido
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