Introdução
O que você precisa saber de cara
A síndrome de Howel–Evans é uma condição extremamente rara que envolve o espessamento da pele nas palmas das mãos e nas solas dos pés (hiperceratose). Esta doença familiar está associada a um alto risco vitalício de câncer de esôfago. Por essa razão, às vezes é conhecida como tilose com câncer de esôfago (TCE).
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Entender a doença
Do básico ao detalhe, leia no seu ritmo
Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Nenhum gene associado encontrado
Os dados genéticos desta condição ainda estão sendo catalogados.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Queratodermia palmoplantar hereditária, tipo Gamborg-Nielsen
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Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Functional Characterization of a Novel In-Frame Indel and a Founder Variant in SERPINB7 Associated With Palmoplantar Keratoderma.
Nagashima-type palmoplantar keratoderma (NPPK) is a hereditary non-epidermolytic keratoderma predominantly reported in East Asian populations. It is mainly caused by biallelic loss-of-function variants in SERPINB7, but the functional impact of certain variants remains unclear. In this study, we performed Sanger sequencing on three unrelated Chinese patients with clinically diagnosed NPPK and identified biallelic pathogenic SERPINB7 variants in all cases. Among these, a novel in-frame indel variant (c.806_814delinsT, p.Ser269_Glu273delinsLeu) and three known founder variants (c.796C>T, c.522dupT, and c.455G>T) were detected. Transcript analysis revealed that the c.455G>T variant, despite being located at the exon-intron 6 junction, functions as a missense variant (p.Gly152Val) without affecting mRNA splicing. Functional studies, including protein structural modeling and legumain protease activity assays, revealed that both variants impaired the inhibitory function of SERPINB7, leading to increased legumain activity. These findings expand the mutational spectrum of SERPINB7 and provide new insights into the pathogenicity of the c.806_814delinsT and c.455G>T variants in the Chinese population.
New gene-based classification of ichthyoses and palmoplantar keratodermas: Hereditary epidermal differentiation disorders.
SASH1 Mutations and Hereditary Disorders of Pigmentation: Review of Literature.
Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by asymptomatic hyper- and hypopigmented macules appearing in infancy and persisting for life. Although mutations in ABCB6 account for many DUH cases, recently, the SAM and SH3 domain-containing 1 (SASH1) gene has emerged as a key player in DUH. Additionally, SASH1 mutations have been associated with the pure-lentiginous phenotype of familial pigmentation. In this review of literature, we found 22 different SASH1 mutations, most inherited in an autosomal dominant manner. These variants cause distinct phenotypes, including DUH, lentiginosis, and rarely, an autosomal recessive syndromic form with alopecia, palmoplantar keratoderma, and increased risk of malignancies. Functional studies have revealed that SASH1 acts as both a tumor suppressor and a pro-melanogenic factor. It modulates key pathways such as p53-POMC-α-MSH-MC1R-MITF and Gαs-SASH1-IQGAP1-E-cadherin pathways, affecting melanosome production, transport, and melanocyte migration. This unique dual role of SASH1 highlights its importance in melanocyte homeostasis and UV-induced pigmentation. Understanding the role of SASH1 in regulating pigmentation can help foster novel therapeutic approaches for these genodermatoses and related pigmentary anomalies, ultimately improving patient care and outcomes.
A signal peptide variant in SLURP1 with dominant-negative effect causes progressive symmetric erythrokeratodermia.
Progressive symmetric erythrokeratodermia (PSEK) is a group of hereditary cornification disorders characterized by symmetrical, progressive erythroderma and hyperkeratosis over the body. Loss-of-function variants in SLURP1, encoding secreted Ly-6/uPAR-related protein 1, is known to cause Mal de Meleda, an autosomal recessive palmoplantar keratoderma. To identify the genetic basis and the pathogenesis of a sporadic patient with PSEK. Whole-exome sequencing and Sanger sequencing were performed to identify the pathogenic variant(s). The expression of SLURP1 was assessed on the patient's skin tissue by immunofluorescence. Western blotting (WB) and immunofluorescence (IF) were performed on eukaryotic overexpression systems to evaluate the signal peptide (SP) cleavage, subcellular localization and secretion of the mutant SLURP1. Combined WB and IF analyses were conducted on cells co-transfected with FLAG-tagged wild-type SLURP1 and untagged SLURP1-Ala22Asp. We identified a de novo heterozygous variant in SLURP1 (c.65A > C, p.Ala22Asp) affecting the first residue before SP cleavage site in a patient with PSEK. This variant abolished the cleavage site of SP, resulting in translocation deficiency to the Golgi apparatus and decreased secretion of the mutant SLURP1. We also found that the SLURP1-Ala22Asp exerted a dominant-negative effect by impeding the SP cleavage of the wild-type SLURP1 and affecting its subcellular localization and secretion in a dose-dependent manner. We reported the first autosomal-dominant variant in SLURP1 associated with a new phenotype of PSEK in a patient, emphasizing the genetic and clinical heterogeneity of SLURP1-associated genodermatoses.
Atypical manifestation of psoriasis in the elderly: possible expression of Mal de Meleda diagnosis review and case report.
Mal de Meleda (MDM) is a rare hereditary skin disorder classified as an autosomal recessive palmoplantar keratoderma, with an estimated prevalence of 1 in 100,000 individuals. It is commonly linked to consanguineous parentage and typically presents during early childhood. The hallmark features of the condition include transient thickening of the palms and soles, skin sclerosis and atrophy, scleroatrophic erythematous lesions, pseudoainhum formation around the digits, and erythema around the mouth. Due to its rarity, many dermatologists may lack clinical familiarity with MDM. Moreover, there is considerable phenotypic similarity between Mal de Meleda and other forms of palmoplantar keratoderma, as well as certain erythrokeratodermas, making clinical differentiation particularly difficult. Therefore, genetic testing to identify causative mutations plays a crucial role in confirming the diagnosis. Genetic alterations in the SLURP1 gene, which encodes the secreted Ly-6/uPAR-related protein 1, have been identified as key contributors to the development of Mal de Meleda (MDM). SLURP1 plays a critical role in maintaining epidermal equilibrium by regulating essential processes such as keratinocyte (KC) proliferation, terminal differentiation, programmed cell death (apoptosis), and cornification. Furthermore, reduced SLURP1 expression has been linked to the pathogenesis of various epithelial cancers, suggesting its broader significance in maintaining epithelial tissue integrity and suppressing tumors. The management of Mal de Meleda remains a clinical challenge, as current therapeutic approaches are largely limited to alleviating symptoms rather than addressing the underlying cause. Systemic retinoids, particularly acitretin, have demonstrated efficacy in reducing epidermal hyperkeratosis and enhancing clinical outcomes. Nonetheless, prolonged administration may lead to significant side effects, necessitating close clinical supervision. This case report contributes to the medical literature by documenting a rare presentation of Mal de Meleda, highlighting the importance of recognizing atypical clinical features and implementing accurate diagnostic and therapeutic interventions. Psoriasis is a chronic, immune-mediated inflammatory dermatosis that exerts a profound effect on patients' quality of life. The disease typically follows a relapsing-remitting course and is frequently associated with a spectrum of comorbid conditions. In pediatric populations, the etiology of psoriasis is multifactorial, involving a combination of genetic susceptibility, environmental triggers, psychosocial stressors, obesity, physical trauma, cutaneous irritation, and exposure to certain pharmacological agents such as lithium, β-blockers, and tumor necrosis factor (TNF) inhibitors. Moreover, systemic inflammatory disorders like Crohn's disease and juvenile idiopathic arthritis have been linked to an increased risk of psoriasis in children. The disease burden is considerable in adults, but poses even greater challenges in pediatric patients, where atypical clinical presentations may hinder timely and accurate diagnosis. It is essential for dermatologists to accurately differentiate Mal de Meleda (MDM) from psoriasis, as these conditions may exhibit overlapping clinical features yet diverge significantly in therapeutic response and long-term prognosis. Distinctive diagnostic clues-such as very early disease onset, autosomal recessive mode of inheritance, and the hallmark transgradient pattern of palmoplantar keratoderma-can aid in distinguishing MDM from the more prevalent psoriasis vulgaris. Although biologic therapies targeting TNF-α and IL-17A have shown limited efficacy in MDM, systemic retinoids continue to represent a clinically effective therapeutic option for managing this rare genodermatosis.
Publicações recentes
Bi-Allelic DSG1 Splice-Site Variant Identified in a Family With Non-Syndromic Striate Palmoplantar Keratoderma.
Phenotypic and genotypic analysis of SERPINA12-related autosomal recessive palmoplantar keratoderma in southwestern China.
Pain Hypersensitivity in SLURP1 and SLURP2 Knock-out Mouse Models of Hereditary Palmoplantar Keratoderma.
A novel mutation in SLURP1 in patients with Mal de Meleda from Turkey.
📚 EuropePMCmostrando 84
Functional Characterization of a Novel In-Frame Indel and a Founder Variant in SERPINB7 Associated With Palmoplantar Keratoderma.
The Journal of dermatologyAtypical manifestation of psoriasis in the elderly: possible expression of Mal de Meleda diagnosis review and case report.
Frontiers in medicineBuschke-Fischer-Brauer Keratoderma: A Case Report of a Rare Skin Disorder.
Clinical case reportsNew gene-based classification of ichthyoses and palmoplantar keratodermas: Hereditary epidermal differentiation disorders.
Journal of the American Academy of DermatologyBi-Allelic DSG1 Splice-Site Variant Identified in a Family With Non-Syndromic Striate Palmoplantar Keratoderma.
The Journal of dermatologyA case report of palmoplantar keratoderma in a 3-year-old girl: A structured approach in primary care settings.
Malaysian family physician : the official journal of the Academy of Family Physicians of MalaysiaSASH1 Mutations and Hereditary Disorders of Pigmentation: Review of Literature.
Pigment cell & melanoma researchA new syndromic case of hearing loss and ectodermal anomalies associated with a recurrent missense variation in GJB6 gene.
Molecular genetics & genomic medicineLoss-of-function variants in DUSP1 encoding dual specificity phosphatase 1 cause palmoplantar keratoderma.
The British journal of dermatologySyndromic epidermal differentiation disorders: a new classification toward pathogenesis-based therapy.
The British journal of dermatologyExploring alternative approaches: A case report on palmoplantar keratoderma treated with unani medicine.
Explore (New York, N.Y.)A signal peptide variant in SLURP1 with dominant-negative effect causes progressive symmetric erythrokeratodermia.
Journal of dermatological scienceSevere palmoplantar keratoderma: a cutaneous complication from sub-optimally controlled type 2 diabetes.
Endocrinology, diabetes & metabolism case reportsResolution of paraneoplastic palmoplantar keratoderma after treating mixed serous neuroendocrine tumor of the pancreas: a case report and literature review.
Dermatology reportsPhenotypic and genotypic analysis of SERPINA12-related autosomal recessive palmoplantar keratoderma in southwestern China.
The Journal of dermatologyPalmoplantar Keratoderma Treated with Individualized Homoeopathic Medicine: A Case Report.
Alternative therapies in health and medicine[Palmoplantar dermatoses: Diagnostic approach in primary care].
SemergenSERPINB7 Deficiency Increases Legumain Activity and Impairs the Epidermal Barrier in Nagashima-Type Palmoplantar Keratoderma.
The Journal of investigative dermatologyPain Hypersensitivity in SLURP1 and SLURP2 Knock-out Mouse Models of Hereditary Palmoplantar Keratoderma.
The Journal of neuroscience : the official journal of the Society for NeuroscienceMutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma.
Clinical, cosmetic and investigational dermatologyHereditary epidermolytic palmoplantar keratosis due to a novel desmoglein-1 mutation: A case report.
Clinical case reportsA novel mutation in SLURP1 in patients with Mal de Meleda from Turkey.
International journal of dermatologyA mutation in CCDC91, Homo sapiens coiled-coil domain containing 91 protein, cause autosomal-dominant acrokeratoelastoidosis.
European journal of human genetics : EJHGUnusual Presentation of Aquagenic Palmoplantar Keratoderma with Overlapping Clinical Features with Hereditary Papulotranslucent Acrokeratoderma in a Young Male.
Indian dermatology online journalThe Depressiveness, Quality of Life and NEO-FFI Scale in Patients with Selected Genodermatoses.
Journal of clinical medicineAn Institution Based Cross-Sectional Observational Aetiological Study Correlating the Clinico-Pathological Findings in Patients Presenting with Acquired Palmoplantar Keratoderma.
Indian journal of dermatologyHereditary Punctate Palmoplantar Keratoderma in Three Generations.
Indian dermatology online journalA Rare Case on Capecitabine Induced Acquired Palmoplantar Keratoderma.
Clinical, cosmetic and investigational dermatologyPalmoplantar keratoderma, pseudo-ainhum and knuckle pads in an African patient: A case report.
SAGE open medical case reportsA Novel Variant in the Desmoplakin Gene in One Case of the Rare Carvajal Syndrome with Dilated Cardiomyopathy: A Case Report and Literature Review.
Clinical, cosmetic and investigational dermatologyA novel SERPINA12 variant and first European patients with diffuse palmoplantar keratoderma.
Journal of the European Academy of Dermatology and Venereology : JEADVMultiple keratotic projections on the palms and soles.
Dermatology online journalA Case Report of Hereditary Palmoplantar Keratoderma with Esophageal Melanosis.
Middle East journal of digestive diseasesIntegration of Phenotype Term Prioritization and Gene Expression Analysis Reveals a Novel Variant in the PERP Gene Associated with Autosomal Recessive Erythrokeratoderma.
GenesProteomic profiling reveals KRT6C as a probable hereterodimer partner for KRT9: New insights into re-classifying epidermolytic palmoplantar keratoderma (EPPK) and a milder form of pachyonychia congenita (PC-K6c) as a group of genetic cutaneous disorders.
Journal of proteomicsA novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1.
Anais brasileiros de dermatologiaSpiny keratoderma: A review of case reports and histopathological descriptions.
Journal of cutaneous pathologyPalmoplantar keratoderma and digital clubbing in 2 sisters with hypertrophic osteoarthropathy.
JAAD case reportsA case of acrodermatitis enteropathica mimicking mutilating palmoplantar keratoderma.
Indian journal of dermatologyInvestigation of Nagashima-type palmoplantar keratoderma in China: A cross-sectional study of 234 patients.
The Journal of dermatologyPalmoplantar Keratoderma: A Molecular Genetic Analysis of Family Cases.
International journal of molecular sciences[Clinical Characteristics and Gene Mutations in 186 Cases of Kindler Syndrome].
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae SinicaeNovel and founder variants of SERPINA12 in Chinese patients with autosomal recessive palmoplantar keratoderma.
The British journal of dermatology[Genetics of complex and syndromic palmoplantar keratoderma].
Annales de biologie cliniqueIsolated hereditary diffuse palmoplantar keratoderma in Hong Kong Chinese patients: a case series.
Hong Kong medical journal = Xianggang yi xue za zhiDesmoplakin and clinical manifestations of desmoplakin cardiomyopathy.
Chinese medical journalAquagenic (pseudo) keratoderma (aquagenic palmoplantar keratoderma, aquagenic wrinkling of palms).
Clinics in dermatologyHereditary palmoplantar keratoderma - phenotypes and mutations in 64 patients.
Journal of the European Academy of Dermatology and Venereology : JEADVDrugs Associated With the Development of Palmoplantar Keratoderma: A Systematic Review.
Journal of cutaneous medicine and surgery[Palmoplantar dermatoses in children].
Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte GebieteHereditary Hearing Impairment with Cutaneous Abnormalities.
GenesA novel frameshift mutation in the FERMT1 gene in a Chinese patient with Kindler syndrome.
Experimental and therapeutic medicineTreatment of hereditary palmoplantar keratoderma: a review by analysis of the literature.
The British journal of dermatologyA Family with Palmar and Plantar Hyperkeratosis: A Quiz.
Acta dermato-venereologicaPunctate Palmoplantar Keratoderma: A Case Report of Type 1 (Buschke-Fischer-Brauer Disease).
Case reports in dermatologyPathogenic FAM83G palmoplantar keratoderma mutations inhibit the PAWS1:CK1α association and attenuate Wnt signalling.
Wellcome open research[Acral melanoma in a patient with hereditary keratoderma of the palms and soles (mal de Meleda): A chance association?].
Annales de dermatologie et de venereologieHereditary Palmoplantar Keratoderma: A Practical Approach to the Diagnosis.
Indian dermatology online journalMal de Meleda: A great imitator.
Clinics in dermatology[Syndromes with scales and keratosis].
Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte GebieteMutation-Proved Clouston Syndrome in a Large Indian Family with a Variant Phenotype.
Indian journal of dermatologyPain mechanisms in hereditary palmoplantar keratodermas.
The British journal of dermatologyImprovement of hereditary palmoplantar keratoderma with oral trametinib.
Pediatric dermatologySymmetrical acral keratoderma revisited: proposal for a new term, 'pigmented carpotarsal hyperkeratosis'.
Journal of the European Academy of Dermatology and Venereology : JEADVVohwinkel syndrome: ichthyosiform variant in a family.
Anais brasileiros de dermatologiaWhole-exome sequencing analysis reveals co-segregation of a COL20A1 missense mutation in a Pakistani family with striate palmoplantar keratoderma.
Genes & genomicsAberrant expression of aquaporin-3 in hereditary papulotranslucent acrokeratoderma and aquagenic palmoplantar keratoderma.
European journal of dermatology : EJDCase of punctate palmoplantar keratoderma type I treated with combination of low-dose oral acitretin and topical salicylic acid and steroid.
The Journal of dermatologyHereditary palmoplantar keratodermas. Part I. Non-syndromic palmoplantar keratodermas: classification, clinical and genetic features.
Journal of the European Academy of Dermatology and Venereology : JEADVCutaneous disorders characterized by elastolysis or loss of elastic tissue.
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDGHereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas - Diagnostic algorithm and principles of therapy.
Journal of the European Academy of Dermatology and Venereology : JEADVPachydermoperiostosis: The value of molecular diagnosis.
Annales de dermatologie et de venereologieHereditary punctate keratoderma: clinical, pathology, treatment and follow-up.
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia[Hereditary epidermolysis bullosa: French national guidelines (PNDS) for diagnosis and treatment].
Annales de dermatologie et de venereologie[Pachyonychia congenita associated with renal artery stenosis and bronchiectasis].
The Pan African medical journalKeratinization Disorders and Genetic Aspects in Palmar and Plantar Keratodermas.
Acta dermatovenerologica Croatica : ADCClinical and molecular investigation of Buschke-Fischer-Brauer in consanguineous Tunisian families.
Journal of the European Academy of Dermatology and Venereology : JEADVIntra-familial phenotypic variability in a Moroccan family with hearing loss and palmoplantar keratoderma (PPK).
Current research in translational medicineImmunohistological study of tight junction protein expression in mal de Meleda.
Ultrastructural pathologyHereditary palmoplantar keratoderma "clinical and genetic differential diagnosis".
The Journal of dermatologyPalmoplantar keratodermas: clinical and genetic aspects.
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDGA novel large deletion combined with a nonsense mutation in a Chinese child with Papillon-Lefèvre syndrome.
Journal of periodontal researchMolecular genetics of alopecias.
Current problems in dermatologyBuschke-Fischer-Brauer Keratoderma: Linear Variety Associated with Hodgkin's Lymphoma.
Indian journal of dermatologyAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
Ainda não temos associações cadastradas para Queratodermia palmoplantar hereditária, tipo Gamborg-Nielsen.
É de uma associação que acompanha esta doença? Fale com a gente →
Comunidades
Grupos ativos de quem convive com esta doença aqui no Raras
Ainda não existe comunidade no Raras para Queratodermia palmoplantar hereditária, tipo Gamborg-Nielsen
Pacientes, familiares e cuidadores se organizam em comunidades pra compartilhar experiências, fazer perguntas e se apoiar. Você pode ser o primeiro.
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Functional Characterization of a Novel In-Frame Indel and a Founder Variant in SERPINB7 Associated With Palmoplantar Keratoderma.
- New gene-based classification of ichthyoses and palmoplantar keratodermas: Hereditary epidermal differentiation disorders.
- SASH1 Mutations and Hereditary Disorders of Pigmentation: Review of Literature.
- A signal peptide variant in SLURP1 with dominant-negative effect causes progressive symmetric erythrokeratodermia.
- Atypical manifestation of psoriasis in the elderly: possible expression of Mal de Meleda diagnosis review and case report.
- Bi-Allelic DSG1 Splice-Site Variant Identified in a Family With Non-Syndromic Striate Palmoplantar Keratoderma.
- Phenotypic and genotypic analysis of SERPINA12-related autosomal recessive palmoplantar keratoderma in southwestern China.
- Pain Hypersensitivity in SLURP1 and SLURP2 Knock-out Mouse Models of Hereditary Palmoplantar Keratoderma.
- A novel mutation in SLURP1 in patients with Mal de Meleda from Turkey.
- Vohwinkel Syndrome.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:86923(Orphanet)
- OMIM OMIM:244850(OMIM)
- MONDO:0009489(MONDO)
- GARD:16767(GARD (NIH))
- Busca completa no PubMed(PubMed)
- Q55782018(Wikidata)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
