RESUMO

BACKGROUND: Ectrodactyly-ectodermal dysplasia-cleft lip/palate (EEC) syndrome mainly affects ectodermal and mesodermal tissues. It is usually manifested as split hands and feet, ectodermal dysplasia, and orofacial clefting, along with other signs and symptoms. A multidisciplinary approach to treatment is required, in which dentists play an important role in identifying and treating various oral conditions that may be genetically linked to or may be the result of EEC syndrome. CASE PRESENTATION: The present case describes the oral condition of a young child suffering from EEC syndrome and presenting with peripheral giant cell granuloma (PGCG) in the mandibular anterior region. After obtaining a thorough medical and family history and a clinical examination, the lesion was surgically excised under local anesthesia. The patient was followed up at periodic intervals for the next twenty four months, during which no recurrence of the lesion was observed. CONCLUSION: This report highlights the role of a dentist in the management of the oral conditions of patients suffering from EEC syndrome.

Assuntos

Fenda Labial , Fissura Palatina , Displasia Ectodérmica , Granuloma de Células Gigantes , Humanos , Fenda Labial/cirurgia , Fenda Labial/complicações , Fenda Labial/patologia , Granuloma de Células Gigantes/patologia , Granuloma de Células Gigantes/cirurgia , Granuloma de Células Gigantes/diagnóstico por imagem , Fissura Palatina/complicações , Fissura Palatina/cirurgia , Fissura Palatina/patologia , Displasia Ectodérmica/complicações , Displasia Ectodérmica/patologia , Masculino , Feminino , Pré-Escolar

RESUMO

RASopathies are a group of related genetic disorders caused by mutations in genes within the RAS/MAPK signaling pathway. This pathway is crucial for cell division, growth, and differentiation, and its disruption can lead to a variety of developmental and health issues. RASopathies present diverse clinical features and pose significant diagnostic and therapeutic challenges. Studying the landscape of biomarkers in RASopathies has the potential to improve both clinical practices and the understanding of these disorders. This review provides an overview of recent discoveries in RASopathy molecular profiling, which extend beyond traditional gene mutation analysis. mRNAs, non-coding RNAs, protein expression patterns, and post-translational modifications characteristic of RASopathy patients within pivotal signaling pathways such as the RAS/MAPK, PI3K/AKT/mTOR, and Rho/ROCK/LIMK2/cofilin pathways are summarized. Additionally, the field of metabolomics holds potential for uncovering metabolic signatures associated with specific RASopathies, which are crucial for developing precision medicine. Beyond molecular markers, we also examine the role of histological characteristics and non-invasive physiological assessments in identifying potential biomarkers, as they provide evidence of the disease's effects on various systems. Here, we synthesize key findings and illuminate promising avenues for future research in RASopathy biomarker discovery, underscoring rigorous validation and clinical translation.

Assuntos

Biomarcadores , Proteínas ras , Humanos , Biomarcadores/metabolismo , Proteínas ras/metabolismo , Proteínas ras/genética , Transdução de Sinais , Mutação , Mancha Vinho do Porto/genética , Mancha Vinho do Porto/metabolismo , Mancha Vinho do Porto/patologia , Síndrome de Costello/genética , Síndrome de Costello/metabolismo , Síndrome de Costello/patologia , Displasia Ectodérmica/genética , Displasia Ectodérmica/metabolismo , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/patologia , Insuficiência de Crescimento/genética , Insuficiência de Crescimento/metabolismo , Animais , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Fácies

RESUMO

Johanson-Blizzard syndrome (JBS) is an autosomal recessive disorder. We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a 2-year-old boy with Johanson-Blizzard syndrome carrying a compound heterozygous mutation of c.3167C>G (p.S1056X) and c.1911 + 14C>G(splicing) in the UBR1 gene. This iPSC line was free of exogenous gene, expressed stemness markers, exhibited differentiation potential, had normal karyotype and harbored the same mutations found in the patient. The iPSC cellline can serve as a disease model in drug development and novel personalized therapies.

Assuntos

Anus Imperfurado , Displasia Ectodérmica , Transtornos do Crescimento , Perda Auditiva Neurossensorial , Células-Tronco Pluripotentes Induzidas , Mutação , Ubiquitina-Proteína Ligases , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Ubiquitina-Proteína Ligases/genética , Transtornos do Crescimento/genética , Transtornos do Crescimento/patologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/patologia , Pré-Escolar , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Anus Imperfurado/genética , Anus Imperfurado/patologia , Heterozigoto , Nariz/patologia , Nariz/anormalidades , Linhagem Celular , Insuficiência Pancreática Exócrina/genética , Insuficiência Pancreática Exócrina/patologia , Surdez/genética , Surdez/patologia , Diferenciação Celular , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Hipotireoidismo , Pancreatopatias

RESUMO

PURPOSE: We aim to explore a potential treatment strategy for hair loss. MATERIALS AND METHODS: A male 6-year-old child was diagnosed with hidrotic ectodermal dysplasia 2 (HED2) caused by GJB6 (p.G11R) mutations. He presented at our clinic with diffuse thinning and fine and brittle hair since birth. Additionally, the child exhibited abnormal development of teeth, fingernails, and toenails. The condition of the child's hair had not improved significantly with age. He was treated with botanical extracts combined with Minoxidil. RESULTS: After one and a half months of treatment, the patient showed remarkable hair growth. CONCLUSIONS: Our team has previously used botanical extracts in combination for the treatment of autosomal recessive wooly hair in children. In the present case, treatment with botanical extract combined with minoxidil was found to be equally efficacious. This case report provides valuable information for future studies on the use of botanical extracts in treating hair loss, as well as a safe and effective potential treatment strategy for children with congenital alopecia.

Assuntos

Alopecia , Displasia Ectodérmica , Minoxidil , Extratos Vegetais , Humanos , Masculino , Criança , Extratos Vegetais/administração & dosagem , Alopecia/tratamento farmacológico , Alopecia/patologia , Displasia Ectodérmica/tratamento farmacológico , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Quimioterapia Combinada , Mutação , Resultado do Tratamento , Conexinas/genética

RESUMO

HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.

Assuntos

Claudinas , Humanos , Masculino , Claudinas/genética , Adulto , Ictiose/genética , Ictiose/patologia , Hipo-Hidrose/genética , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Linhagem , Fenótipo

RESUMO

Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) is an exceedingly rare condition associated with mutations in the PVL4 gene. It is characterised by sparse, brittle hair, eyebrows and eyelashes, abnormal dentition and nails, along with bilateral cutaneous syndactyly involving the fingers and toes. We report a 2-year-old girl who presented to us with bilateral complete simple syndactyly of the third and fourth web spaces of the hands, along with bilateral syndactyly of both feet involving the second to fourth toes. Upon examination, sparse hair and eyebrows, along with abnormal dentition, were noted. Thorough clinical examination and genetic analysis were conducted on the affected child and her father, who exhibited similar clinical features. Genetic analysis revealed a homozygous nonsense mutation in the PVL4 gene in both individuals. According to the literature, EDSS1 has been reported in only 10 families worldwide, and there are no reported cases from India. Level of Evidence: Level V (Therapeutic).

Assuntos

Displasia Ectodérmica , Sindactilia , Pré-Escolar , Feminino , Humanos , Códon sem Sentido , Displasia Ectodérmica/genética , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/patologia , Sindactilia/genética , Sindactilia/diagnóstico , Sindactilia/patologia

RESUMO

Pathogenic variants in NOTCH1 are associated with non-syndromic congenital heart disease (CHD) and Adams-Oliver syndrome (AOS). The clinical presentation of individuals with damaging NOTCH1 variants is characterized by variable expressivity and incomplete penetrance; however, data on systematic phenotypic characterization are limited. We report the genotype and phenotype of a cohort of 33 individuals (20 females, 13 males; median age 23.4 years, range 2.5-68.3 years) from 11 families with causative NOTCH1 variants (9 inherited, 2 de novo; 9 novel), ascertained from a proband with CHD. We describe the cardiac and extracardiac anomalies identified in these 33 individuals, only four of whom met criteria for AOS. The most common CHD identified was tetralogy of Fallot, though various left- and right-sided lesions and septal defects were also present. Extracardiac anomalies identified include cutis aplasia (5/33), cutaneous vascular anomalies (7/33), vascular anomalies of the central nervous system (2/10), Poland anomaly (1/33), pulmonary hypertension (2/33), and structural brain anomalies (3/14). Identification of these findings in a cardiac proband cohort supports NOTCH1-associated CHD and NOTCH1-associated AOS lying on a phenotypic continuum. Our findings also support (1) Broad indications for NOTCH1 molecular testing (any familial CHD, simplex tetralogy of Fallot or hypoplastic left heart); (2) Cascade testing in all at-risk relatives; and (3) A thorough physical exam, in addition to cardiac, brain (structural and vascular), abdominal, and ophthalmologic imaging, in all gene-positive individuals. This information is important for guiding the medical management of these individuals, particularly given the high prevalence of NOTCH1 variants in the CHD population.

Assuntos

Cardiopatias Congênitas , Linhagem , Fenótipo , Receptor Notch1 , Humanos , Receptor Notch1/genética , Masculino , Feminino , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Adulto , Adolescente , Pré-Escolar , Criança , Pessoa de Meia-Idade , Idoso , Mutação , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Displasia Ectodérmica/diagnóstico , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Deformidades Congênitas dos Membros/diagnóstico , Dermatoses do Couro Cabeludo/congênito

RESUMO

Adams-Oliver syndrome is a rare inherited condition characterized by scalp defects and limb abnormalities. It is caused by variants in different genes such as ARHGAP31. Here, we used an interdisciplinary approach to study a family with lower limb anomalies. We identified a novel variant in the ARHGAP31 gene that is predicted to result in a truncated protein with a constitutively activated catalytic site due to the loss of 688 amino acids involved in the C-terminal domain, essential for protein auto-inhibition. Pathogenic variants in ARHGAP31 exon 12, leading to a premature protein termination, are associated with Adams-Oliver syndrome. Bioinformatic analysis was useful to elucidate the impact of the identified genetic variant on protein structure. To better understand the impact of the identified variant, 3D protein models were predicted for the ARHGAP31 wild type, the newly discovered variant, and other pathogenetic alterations already reported. Our study identified a novel variant probably involved in Adams-Oliver syndrome and increased the evidence on the phenotypic variability in patients affected by this syndrome, underlining the importance of translational research, including experimental and bioinformatics analyses. This strategy represents a successful model to investigate molecular mechanisms involved in syndrome occurrence.

Assuntos

Displasia Ectodérmica , Proteínas Ativadoras de GTPase , Deformidades Congênitas dos Membros , Fosfoproteínas , Dermatoses do Couro Cabeludo , Feminino , Humanos , Masculino , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Proteínas Ativadoras de GTPase/genética , Deformidades Congênitas dos Membros/genética , Mutação , Linhagem , Fenótipo , Dermatoses do Couro Cabeludo/genética , Dermatoses do Couro Cabeludo/congênito , Dermatoses do Couro Cabeludo/patologia

RESUMO

Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly (TEBC) syndrome is a rare autosomal dominant condition, recently linked to the protein kinase D1 (PRKD1) gene. The phenotype of TEBC remains incomplete at this point. Our aim is to improve the characterization of the clinical and molecular aspects of the TEBC syndrome. We report on the 8th patient carrying a heterozygous de novo variation of PRKD1 c.2134G > A, p. (Val712Met) identified by trio exome sequencing. The proband presents with partial atrioventricular septal defect, brachydactyly, ectodermal dysplasia, telangiectasia that developed in childhood, intellectual disability with microcephaly, multicystic renal dysplasia and moderate hormonal resistance. In view of this 8th description and review of the literature, it appears that neurodevelopmental disorders and microcephaly are frequently associated with PRKD1 missense variants, adding to the four main clinical signs described initially in the TEBC syndrome. Further descriptions are required to confirm the observed endocrine and kidney abnormalities. This should contribute to a more comprehensive understanding of the phenotypic spectrum and may help establish genotype-phenotype correlations. In the context of genotype-first strategy, accurate patient descriptions are fundamental. Characterization of specific syndromic associations is essential for variant interpretation support and patient follow-up, even in very rare diseases, such as the TEBC syndrome.

Assuntos

Displasia Ectodérmica , Cardiopatias Congênitas , Humanos , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Fenótipo , Braquidactilia/genética , Braquidactilia/patologia , Masculino , Telangiectasia/genética , Telangiectasia/patologia , Feminino , Mutação de Sentido Incorreto , Síndrome , Microcefalia/genética , Microcefalia/patologia , Criança , Proteína Quinase C

RESUMO

A 27-year-old multiparous woman conceived her fetus naturally. Early second-trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy was artificially terminated at 19 weeks of gestation because of the abnormalities based on the parents' wishes. The parents desired whole-exome sequencing to detect a causative gene using the umbilical cord and the parents' saliva. Compound heterozygous variants (NC_000003.11(NM_052989.3):c.230 T > G/NC_000003.11(NM_052985.4):c.1178A > T) were identified. We described a fetus with a novel compound heterozygous variant in IFT122. The phenotype of this case was severer than of other types of cranioectodermal dysplasia.

Assuntos

Displasia Ectodérmica , Sequenciamento do Exoma , Fenótipo , Humanos , Feminino , Gravidez , Adulto , Displasia Ectodérmica/genética , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/patologia , Ultrassonografia Pré-Natal , Mutação , Heterozigoto , Osso e Ossos/anormalidades , Craniossinostoses

RESUMO

Biallelic pathogenic variants in MAP3K20, which encodes a mitogen-activated protein kinase, are a rare cause of split-hand foot malformation (SHFM), hearing loss, and nail abnormalities or congenital myopathy. However, heterozygous variants in this gene have not been definitively associated with a phenotype. Here, we describe the phenotypic spectrum associated with heterozygous de novo variants in the linker region between the kinase domain and leucine zipper domain of MAP3K20. We report five individuals with diverse clinical features, including craniosynostosis, limb anomalies, sensorineural hearing loss, and ectodermal dysplasia-like phenotypes who have heterozygous de novo variants in this specific region of the gene. These individuals exhibit both shared and unique clinical manifestations, highlighting the complexity and variability of the disorder. We propose that the involvement of MAP3K20 in endothelial-mesenchymal transition provides a plausible etiology of these features. Together, these findings characterize a disorder that both expands the phenotypic spectrum associated with MAP3K20 and highlights the need for further studies on its role in early human development.

Assuntos

Craniossinostoses , Displasia Ectodérmica , Perda Auditiva Neurossensorial , Heterozigoto , Humanos , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/patologia , Masculino , Feminino , Craniossinostoses/genética , Fenótipo , Pré-Escolar , Deformidades Congênitas dos Membros/genética , Criança , Mutação , Lactente , MAP Quinase Quinase Quinases/genética

Assuntos

Displasia Ectodérmica , Feminino , Humanos , Displasia Ectodérmica/patologia , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Pele/patologia , Pré-Escolar

RESUMO

In this study, we retrospectively analyzed the clinical data of a newborn with aplasia cutis congenita (ACC) to provide insights for diagnosing and treating the disease. It is believed that ACC with an intact skull and a skin defect diameter of less than 2 cm can be treated conservatively. The main strategies include local disinfection and regular dressing changes to promote epithelial regeneration. The lesion can heal over weeks or months through epithelization adjacent to the defect tissue, resulting in a healed contracture scar with a smooth, hairless surface that can be surgically removed later. For children with large scalp defects or skull defects, skin transplantation, free flap, and cranioplasty can be performed to repair the wound and restore the tissue structure. It is worth mentioning that although this child had a scalp defect larger than 2 cm, conservative treatment still had a significant effect. This suggests that conservative treatment can be considered as the first choice for ACC neonates without skull defects, and surgical treatment can be considered when necessary.

Assuntos

Displasia Ectodérmica , Recém-Nascido , Criança , Humanos , Estudos Retrospectivos , Displasia Ectodérmica/patologia , Displasia Ectodérmica/cirurgia , Transplante de Pele , Crânio/anormalidades , Crânio/patologia , Crânio/cirurgia

RESUMO

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder. AEC is caused by mutations in the TP63 gene that encodes the tumor suppressor p63 protein, itself involved in the regulation of epidermal proliferation, development, and differentiation. We present here a typical AEC case of a four-year-old girl with extensive skin erosions and erythroderma of the scalp and the trunk, and to a lesser extent of the limbs, nail dystrophy on the fingers and toes, xerophthalmia, a high-arched palate, oligodontia, and hypohidrosis. Mutation analysis of the TP63 gene detected a de novo missense mutation in exon 14 (c.1799G>T; p.Gly600Val). We discuss the phenotype-genotype correlation by presenting the clinical features of AEC in the patient, and the effect of the detected mutation in p63 structure and function using protein structural modeling, in view of similar cases in the literature. We performed a molecular modeling study in order to link the effect on the protein structure level of the missense mutation G600V. We noted that the introduction of the bulkier Valine residue in place of the slim Glycine residue caused a significantly altered 3D conformational arrangement of that protein region, pushing away the adjacent antiparallel α helix. We propose that the introduced locally altered structure of the G600V mutant p63 has a significant functional effect on specific protein-protein interactions, thus affecting the clinical phenotype.

Assuntos

Fenda Labial , Fissura Palatina , Displasia Ectodérmica , Humanos , Fenda Labial/genética , Fenda Labial/patologia , Fissura Palatina/diagnóstico , Fissura Palatina/genética , Fissura Palatina/patologia , Fatores de Transcrição/genética , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Proteínas Supressoras de Tumor/genética , Estudos de Associação Genética

RESUMO

ABSTRACT: Cutaneous meningioma, characterized by ectopic meningothelial cells in the dermis or subcutis, is a rare neoplasm. Generally, the most common location for cutaneous meningioma is the scalp. We report a case of cutaneous meningioma presenting as soft, light red, atrophic, and smooth patches with central blue spots. On histological examination, the tumor consisted largely of epithelioid cells, whorls, nests, and syncytial sheets of meningothelial cells. HMB-45, Melan-A, and S100 were negative; epithelial membrane antigen and somatostatin receptor 2 were positive. Ultimately, histopathologic examination and immunohistochemistry results supported a diagnosis of cutaneous meningioma. In addition, dermal dysplasia was observed above the tumor, manifested by thinning of the dermis and loss of appendages. No abnormalities were found on brain magnetic resonance imaging. Cutaneous meningioma is an extremely rare tumor, and its manifestation as an atrophic patch is even rarer. There have been mainly clinical reports of cutaneous meningioma. This was a rare case of focal aplasia cutis congenita with cutaneous meningioma. For cutaneous meningioma to be diagnosed earlier, there needs to be greater public awareness about the condition.

Assuntos

Displasia Ectodérmica , Neoplasias Meníngeas , Meningioma , Neoplasias do Sistema Nervoso Periférico , Neoplasias Cutâneas , Humanos , Meningioma/patologia , Neoplasias Cutâneas/patologia , Displasia Ectodérmica/patologia , Neoplasias Meníngeas/patologia

RESUMO

OBJECTIVE: The purpose of this study was to identify a pathogenic mutation located in TP63 in a nuclear Han Chinese family. DESIGN: Whole-exome sequencing and Sanger sequencing were performed to identify candidate variants. The AlphaFold and PyMOL predicted the three-dimensional structure of the protein. Single-cell RNA-sequencing data and spatiotemporal transcriptomic atlas were used to generate the dissection of candidate gene expression at single-cell resolution. Significant genes (Pearson's coefficient ≥0.8 and P < 0.05) were identified for Gene Ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathways analysis. RESULTS: A heterozygous missense variant at TP63 exon 8 (c.1010 G>A:p.Arg337Gln) was identified in the proband. This variant was predicted deleterious and likely to impair the local stability of the protein. In addition, single-cell RNA-sequencing indicated that TP63 was highly expressed in skin tissues. Furthermore, spatial transcriptome data of mice embryos showed TP63 was mainly enriched in the mucosal epithelium, thymus, epidermis, mesenchyme, and surface ectoderm. GO and KEGG pathway annotation analysis revealed that TP63 played a positive role in the process of ectoderm via the TGF-beta signaling pathway. CONCLUSIONS: The missense variant of TP63 (c.1010 G>A:p.Arg337Gln) was associated with ectodermal dysplasia.

Assuntos

Displasia Ectodérmica , Fatores de Transcrição , Humanos , Animais , Camundongos , Fatores de Transcrição/genética , População do Leste Asiático , Proteínas Supressoras de Tumor/genética , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Mutação , Mutação de Sentido Incorreto , Linhagem

RESUMO

Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.

Assuntos

Conexinas , Displasia Ectodérmica , Humanos , Conexina 30/genética , Conexinas/genética , População do Leste Asiático , Displasia Ectodérmica/genética , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/patologia , Fenótipo

Assuntos

Displasia Ectodérmica , Melanoma , Neoplasias Cutâneas , Humanos , Displasia Ectodérmica/patologia , Neoplasias Cutâneas/diagnóstico , Melanoma/diagnóstico , Melanoma Maligno Cutâneo

RESUMO

We systematically delineated the prenatal phenotype, and obstetrical and neonatal outcomes of the RASopathy cardio-facio-cutaneous (CFC) syndrome. A comprehensive, retrospective medical history survey was distributed to parents of children with confirmed CFC in collaboration with CFC International, Inc. Data were collected on CFC gene variant, maternal characteristics, pregnancy course, delivery, and neonatal outcomes with the support of medical records. We identified 43 individuals with pathogenic variants in BRAF (81%), MEK1 (14%), or MEK2 (5%) genes. The median age was 8.5 years. Hyperemesis gravidarum, gestational diabetes, gestational hypertension, and preeclampsia occurred in 5/43 (12%), 4/43 (9%), 3/43 (7%), and 3/43 (7%) of pregnancies, respectively. Second and third trimester ultrasound abnormalities included polyhydramnios, macrocephaly, macrosomia, and renal and cardiac abnormalities. Delivery occurred via spontaneous vaginal, operative vaginal, or cesarean delivery in 15/42 (36%), 7/42 (16%), and 20/42 (48%), respectively. Median gestational age at delivery was 37 weeks and median birth weight was 3501 grams. Germline pathogenic vaiants had mutiple congenital consequences including polyhydramnios, renal and cardiac abnormalities, macrosomia, and macrocephaly on second and third trimester ultrasound. Elevated rates of operative delivery and neonatal complications were also noted. Understanding and defining a prenatal phenotype may improve prenatal prognostic counseling and outcomes.

Assuntos

Displasia Ectodérmica , Cardiopatias Congênitas , Megalencefalia , Poli-Hidrâmnios , Humanos , Gravidez , Feminino , Estudos Retrospectivos , Macrossomia Fetal , Proteínas Proto-Oncogênicas B-raf/genética , Displasia Ectodérmica/diagnóstico , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Fácies , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia

RESUMO

Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.

Assuntos

Humanos , Conexina 30/genética , Conexinas/genética , População do Leste Asiático , Displasia Ectodérmica/patologia , Fenótipo