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The Journal of Dermatology Feb 2022
Topics: Blister; Epidermolysis Bullosa; Female; Humans; Middle Aged; Periodontal Diseases; Photosensitivity Disorders; Syndactyly
PubMed: 34791714
DOI: 10.1111/1346-8138.16236 -
Annals of Medicine and Surgery (2012) May 2023Kindler syndrome is a rare autosomal recessive inherited disease. The authors report a case with unique presentation that has never reported before in the medical...
Kindler syndrome is a rare autosomal recessive inherited disease. The authors report a case with unique presentation that has never reported before in the medical Literatur" lanugo hair". This is a case of a 13-year-old Syrian child, who presented with difuse fine face hair, and serious urinary complications. Kindler syndrome is characterized by acral skin blistering beginning at birth, diffuse cutaneous atrophy, photosensitivity, poikiloderma, and various mucosal findings. Highlighting a set of clinical diagnostic criteria; which is used only if a genetic test is not available.
PubMed: 37229095
DOI: 10.1097/MS9.0000000000000503 -
Frontiers in Oncology 2022gene mutations are associated with a hereditary fibrosing poikiloderma known to cause poikiloderma, tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP). In... (Review)
Review
gene mutations are associated with a hereditary fibrosing poikiloderma known to cause poikiloderma, tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP). In addition, the overexpression of FAM111B has been associated with cancer progression and poor prognosis. This review inferred the molecular function of this gene's protein product and mutational dysfunction in fibrosis and cancer based on recent findings from studies on this gene. In conclusion, FAM111B represents an uncharacterized protease involved in DNA repair, cell cycle regulation, and apoptosis. The dysregulation of this protein ultimately leads to fibrotic diseases like POIKTMP and cancers the disruption of these cellular processes by the mutation of the gene. Hence, it should be studied in the context of these diseases as a possible therapeutic target.
PubMed: 35860584
DOI: 10.3389/fonc.2022.932167 -
Actas Dermo-sifiliograficas Nov 2020Kindler syndrome is a very rare form of bullous epidermolysis. It is a hereditary condition caused by a mutation in the FERMT1 gene that encodes the protein kindlin-1....
Kindler syndrome is a very rare form of bullous epidermolysis. It is a hereditary condition caused by a mutation in the FERMT1 gene that encodes the protein kindlin-1. It is clinically characterized by trauma-induced blistering, diffuse skin atrophy, poikiloderma, pseudosyndactyly, and photosensitivity. The most common mucosal manifestations are conjunctivitis, ectropion, hemorrhagic gingivitis, periodontal disease, premature tooth loss, and severe colitis. We present the first 4 cases of Kindler syndrome diagnosed at the Instituto Nacional de Salud del Niño in Lima, Peru. These cases highlight the unique clinical presentation and multiple manifestations of this disease and show how a multidisciplinary management approach kept symptoms under control and significantly improved patient quality of life.
Topics: Blister; Epidermolysis Bullosa; Humans; Membrane Proteins; Neoplasm Proteins; Periodontal Diseases; Peru; Photosensitivity Disorders; Quality of Life
PubMed: 32861675
DOI: 10.1016/j.ad.2019.04.013 -
Dermatology Practical & Conceptual Jul 2022Dermoscopy is a noninvasive and easy to apply technique that allows in vivo magnification of the skin and thus observation of morphologic structures invisible to the...
INTRODUCTION
Dermoscopy is a noninvasive and easy to apply technique that allows in vivo magnification of the skin and thus observation of morphologic structures invisible to the naked eye. Recently, it gained popularity for evaluation of inflammatory skin conditions. In the field of connective tissue diseases, dermoscopy has been used mainly as a simple and accessible substitute of nailfold capillaroscopy.
OBJECTIVES
The aim of the present study is to expand the application of dermoscopy in patients with dermatomyositis (DM) beyond the usual nailfold examination. A clinico-dermoscopic correlation between clinical signs of skin affection and dermoscopic features is also suggested.
METHODS
A total of 29 patients with DM were enrolled in this descriptive prospective study, conducted over a 3-year period. Dermoscopy was performed by a DermLite DL1 dermatoscope on polarization mode, attached to One Plus 3T camera. The following skin lesions were examined: periungual affection, scalp DM, Gottron papules, palmar papules, poikiloderma and auricular changes.
RESULTS
Dermoscopy detected predominantly advanced nail fold capillary changes - giant capillaries (79%), microhemorrhages (46%) and avascular areas (25%). The most prevalent trichoscopic features were enlarged tortuous capillaries (64%), interfollicular scales (50%) and peripilar casts and tufting (36%). Among the other skin lesions assessed in this study - Gottron papules were present in 20 patients, poikiloderma in 11, palmar papules in 4 and auricular lesions in 4 patients.
CONCLUSIONS
The use of dermoscopy for clinical evaluation of skin lesions in DM enhances diagnostic accuracy and elucidates poorly known characteristics of the disease.
PubMed: 36159137
DOI: 10.5826/dpc.1203a142 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Apr 2022Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS....
Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(=0.234,=0.023),palmoplantar keratoderma(=0.325,=0.001),webbing/pseudoainhum(=0.247,=0.016),dysphagia(=0.333,=0.001),urethral stricture(=0.280,=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(=11.292,=0.001)and anal stenosis(=4.014,=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).
Topics: Adolescent; Adult; Ainhum; Blister; Carcinoma, Squamous Cell; Child; Constriction, Pathologic; Deglutition Disorders; Epidermolysis Bullosa; Female; Humans; Inflammation; Keratoderma, Palmoplantar; Male; Membrane Proteins; Mutation; Neoplasm Proteins; Periodontal Diseases; Photosensitivity Disorders; Urethral Stricture; Young Adult
PubMed: 35538757
DOI: 10.3881/j.issn.1000-503X.14761 -
Frontiers in Medicine 2021Poikiloderma with neutropenia (PN) is a very rare genetic disorder mainly characterized by poikiloderma and congenital neutropenia, which explains the recurrence of...
Poikiloderma with neutropenia (PN) is a very rare genetic disorder mainly characterized by poikiloderma and congenital neutropenia, which explains the recurrence of respiratory infections and risk of developing bronchiectasis. Patients are also prone to develop hematological and skin cancers. Here, we present the case of a patient, the only child of apparently unrelated Serbian parents, affected by PN resulting from the homozygous mutation NM_024598.3:c.243G>A (p.Trp81Ter) of ; early onset of poikiloderma (1 year of age) was associated with cutaneous mastocytosis. We also provide a review of the literature on this uncommon condition with a focus on dermatological findings.
PubMed: 34179048
DOI: 10.3389/fmed.2021.680363 -
Matrix Biology : Journal of the... May 2021Epidermolysis bullosa (EB) is a genotypically heterogeneous group of disorders characterized by cutaneous blistering and erosions with a tremendous spectrum of severity....
Kindler epidermolysis bullosa-like skin phenotype and downregulated basement membrane zone gene expression in poikiloderma with neutropenia and a homozygous USB1 mutation.
Epidermolysis bullosa (EB) is a genotypically heterogeneous group of disorders characterized by cutaneous blistering and erosions with a tremendous spectrum of severity. One of the distinct forms of EB, Kindler EB (KEB), manifests with blistering and poikiloderma; this subtype of EB is caused by mutations in the FERMT1 gene encoding kindlin-1. In this study, we investigated a patient clinically diagnosed as KEB with reduced FERMT1 gene expression and intensity of immunostaining for kindlin-1. Transmission electron microscopy showed lamina densa reduplication, frequently observed in KEB. However, no mutations were identified in FERMT1 in this patient with consanguineous parents, and this gene resided outside of genomic regions of homozygosity (ROH). Instead, whole-exome sequencing and homozygosity mapping identified a homozygous sequence variant at the +4 position of intron 2 in the USB1 gene, encoding an exoribonuclease required for processing of U6 snRNA, a critical component of spliceosomes. Examination of the patient's RNA by RNA-Seq confirmed the pathogenicity of this variant, causing aberrant splicing predicted to result in loss of function of USB1. Mutations in this gene have been reported in patients with poikiloderma and neutropenia, with a few reported cases in association with skin fragility, a condition distinct from the KEB phenotype. Transcriptome analysis revealed that several genes, expressed in the cutaneous basement membrane zone and previously associated with different subtypes of EB, were differentially downregulated at the mRNA level. EB-associated mRNA downregulation was confirmed at protein levels by skin immunofluorescence. These observations provide a novel mechanism for blistering and erosions in the skin as a result reduced presence of adhesion complexes critical for stable association of epidermis and dermis at the level of cutaneous basement membrane zone.
Topics: Basement Membrane; Epidermolysis Bullosa; Gene Expression; Humans; Membrane Proteins; Mutation; Neoplasm Proteins; Neutropenia; Phenotype; Phosphoric Diester Hydrolases; Skin Abnormalities
PubMed: 34004352
DOI: 10.1016/j.matbio.2021.05.002 -
Experimental Dermatology May 2022Mutations in the human FAM111B gene are associated with a rare, hereditary multi-systemic fibrosing disease, POIKTMP. To date, there are ten POIKTMP-associated FAM111B... (Review)
Review
Mutations in the human FAM111B gene are associated with a rare, hereditary multi-systemic fibrosing disease, POIKTMP. To date, there are ten POIKTMP-associated FAM111B gene mutations reported in thirty-six patients from five families globally. To investigate the clinical significance of these mutations, we summarized individual cases by clinical features and position of the reported FAM111B gene mutations as those within and outside the putative protease domain (MWPPD and MOPPD respectively). MWPPD cases had more clinical manifestations than MOPPD (25 versus 18). Although the most common clinical features of poikiloderma, alopecia and hypohidrosis overall occurred in 94%, 86% and 75% of all cases with no significant differences between the MOPPD and MWPPD group, less common features included life-threatening (pulmonary fibrosis 47% vs. 13%; liver abnormalities specifically cirrhosis 26% vs. 7%) and physically disabling conditions (myopathy 53% vs. 20%; tendon contracture 55% vs. 7%) were more common in MWPPD cases. Similarly, the only 2 cases of POIKTMP with fatal pancreatic cancers were both only in the MWPPD group. This review thus suggests that mutations within the putative protease domain of the FAM111B protein are associated with a broader range of clinical features and may predict increased POIKTMP severity and a poorer prognosis.
Topics: Cell Cycle Proteins; Humans; Mutation; Peptide Hydrolases; Severity of Illness Index; Skin Diseases, Genetic
PubMed: 35122327
DOI: 10.1111/exd.14537 -
PLOS Global Public Health 2023There is still a lack of research in Vietnam on the autoantibody profile of dermatomyositis (DM) and its association with clinical and subclinical characteristics....
There is still a lack of research in Vietnam on the autoantibody profile of dermatomyositis (DM) and its association with clinical and subclinical characteristics. Therefore, we conducted this study to investigate clinical and subclinical correlations with autoantibodies in DM patients. 72 DM patients at Vietnam National Hospital of Dermatology and Venereology (NHDV) from March 2019 to September 2021 were included in this cross-sectional study. Clinical manifestations and laboratory test results of the patients were obtained at the time of visit. Of these, 63 patients were tested for the presence of autoantibodies using an Immunoblot assay. Our findings show that the average age of patients was 41.7 years. The female-male ratio was 1.7:1. The most common skin and muscle manifestations were myalgia (79.2%), heliotrope rash (62.5%), shawl sign (61.1%), Gottron's sign (59.7%), muscle weakness (59.7%), Gottron's papule (52.8%), periungual telangiectasia (41.7%), V-sign (38.9%), poikiloderma (26.4%), periungual fissures (20.8%), Raynaud's phenomenon (15.3%). Among the 63 patients tested for autoantibodies, myositis-specific antibodies (MSAs) were found in 71.4% of the serum samples, and myositis-associated antibodies (MAAs) in 36.5%. Anti-TIF1γ antibody accounted for the highest percentage (28.6%), followed by anti-Ro52 (22.2%), anti-synthetase (17.5%), anti-Mi-2 and anti-MDA5 (both 14.3%). Anti-synthetase antibodies (ARS-Abs) showed a significant association with arthralgia, fever, and Raynaud's phenomenon, while anti-TIF1γ antibodies showed a strong association with V-sign and poikiloderma (p<0.05). Clinical features in dermatomyositis are heterogeneous. Our study results show some associations between clinical features and autoantibodies in patients with DM. The analysis of DM-related autoantibodies is clinically useful, will be essential for the approaches to diagnosis, and management of DM patients.
PubMed: 36962887
DOI: 10.1371/journal.pgph.0000979