scholarly journals Novel folliculin gene mutations in Polish patients with Birt–Hogg–Dubé syndrome

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Elżbieta Radzikowska ◽  
Urszula Lechowicz ◽  
Jolanta Winek ◽  
Lucyna Opoka
Keyword(s):  
Gene Mutations ◽  
Skin Lesions ◽  
Renal Angiomyolipoma ◽  
Inherited Disease ◽  
First Case ◽  
Renal Tumours ◽  
Pulmonary Cysts ◽  
Frequent Mutations ◽  
History Of ◽  
The Mean

Abstract Background Birt–Hogg–Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS. Materials and methods The first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations. Results BHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41). Conclusions All analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified.

Novel Folliculin Gene Mutations in Polish Patients With Birt-hogg-dubé Syndrome

2021 ◽  
Author(s):  
Elzbieta Radzikowska ◽  
Urszula Lechowicz ◽  
Jolanta Winek ◽  
Lucyna Opoka
Keyword(s):  
Gene Mutations ◽  
Skin Lesions ◽  
Renal Angiomyolipoma ◽  
Inherited Disease ◽  
First Case ◽  
Renal Tumours ◽  
Pulmonary Cysts ◽  
Frequent Mutations ◽  
History Of ◽  
The Mean

Abstract Birt-Hogg-Dubé syndrome (BHDS) is a rare, autosomal dominant, inherited disease caused by mutations in the folliculin gene (FLCN). The disease is characterised by skin lesions (fibrofolliculomas, trichodiscomas, acrochordons), pulmonary cysts with pneumothoraces and renal tumours. We present the features of Polish patients with BHDS.Materials and MethodsThe first case of BHDS in Poland was diagnosed in 2016. Since then, 15 cases from 10 families have been identified. Thirteen patients were confirmed via direct FLCN sequencing, and two according to their characteristic clinical and radiological presentations.ResultsBHDS was diagnosed in 15 cases (13 women and 2 men) from 10 families. The mean ages at the time of first pneumothorax and diagnosis were 38.4 ± 13.9 and 47.7 ± 13 years, respectively. Five patients (33%) were ex-smokers (2.1 ± 1.37 packyears), and 10 (67%) had never smoked cigarettes. Twelve patients (83%) had a history of recurrent symptomatic pneumothorax. Three patients had small, asymptomatic pneumothoraces, which were only detected upon computed tomography examination. All patients had multiple bilateral pulmonary cysts, distributed predominantly in the lower and middle, peripheral, and subpleural regions of the lungs. Generally, patients exhibited preserved lung function. Skin lesions were seen in four patients (27%), one patient had renal angiomyolipoma, and one had bilateral renal cancer. Different mutations of the FLCN gene were identified (mainly in exon 6), with two novel heterozygous variants: c.490delA p.(Arg164GlyTer13) and c.40delC p.(His14ThrsfTer41). ConclusionsAll analysed patients with BHDS presented with lung lesions and with less frequent skin and renal lesions than previously reported in other populations. In addition, more frequent mutations located in exon 6 were detected, and two novel FLCN gene mutations were identified.

scholarly journals Xeroderma Pigmentosum with Severe Neurological Manifestations/De Sanctis–Cacchione Syndrome and a Novel XPC Mutation

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Esteban Uribe-Bojanini ◽  
Sara Hernandez-Quiceno ◽  
Alicia María Cock-Rada
Keyword(s):  
Xeroderma Pigmentosum ◽  
Excision Repair ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Panel Testing ◽  
First Case ◽  
Skin Malignancy ◽  
Increased Risk ◽  
History Of

Several genetic disorders caused by defective nucleotide excision repair that affect the skin and the nervous system have been described, including Xeroderma Pigmentosum (XP), De Sanctis–Cacchione syndrome (DSC), Cockayne syndrome, and Trichothiodystrophy. Cutaneous photosensitivity with an increased risk of skin malignancy is a common feature of these disorders, but clinical manifestations commonly overlap these syndromes. Several genes have been found to be altered in these pathologies, but we lack more genotype-phenotype correlations in order to make an accurate diagnosis. Very few cases of DSC syndrome have been reported in the literature. We present a case of a 12-year-old Colombian male, with multiple skin lesions in sun-exposed areas from the age of 3 months and a history of 15 skin cancers. He also displayed severe neurologic abnormalities (intellectual disability, ataxia, altered speech, and hyperreflexia), short stature, and microcephaly, which are features associated with DSC. Genetic testing revealed a novel germline mutation in the XP-C gene (c.547A>T). This is the first case of an XP-C mutation causing De Sanctis–Cacchione syndrome. Multigene panel testing is becoming more widely available and accessible in the clinical setting and will help rapidly unveil the molecular etiology of these rare genetic disorders.

The Burden of Psoriasis in Canada: Insights from the pSoriasis Knowledge IN Canada (SKIN) Survey

2009 ◽  
Vol 13 (5) ◽  
pp. 235-252 ◽  
Author(s):  
Charles W. Lynde ◽  
Yves Poulin ◽  
Lyn Guenther ◽  
Christine Jackson
Keyword(s):  
Telephone Survey ◽  
Burden Of Illness ◽  
Skin Lesions ◽  
Severe Psoriasis ◽  
Similar Data ◽  
Daily Lives ◽  
Substantial Problem ◽  
History Of Disease ◽  
History Of ◽  
The Mean

Background: Although some data addressing the burden of illness associated with psoriasis and psoriatic arthritis (PsA) have been reported for American and European patient populations, similar data have been lacking for Canadians with these diseases. Objective: We sought to characterize the natural history of disease in a sample of Canadians with a history of moderate to severe psoriasis, with or without diagnosed PsA or other recognized comorbid conditions, and to identify factors that influenced their perception of psoriasis as a problem in their daily lives. Methods: A nationwide telephone survey, pSoriasis Knowledge IN Canada (SKIN), was conducted between April 30 and June 2, 2007, on 500 people who indicated that they had been diagnosed with psoriasis and that their skin lesions had at some time affected an area at least as large as three palms of their hand (3% of body surface area [BSA]). Results: The mean age at diagnosis for psoriasis among SKIN survey respondents was 28 years, with 31% (155 of 500) indicating that they developed the disease prior to age 18 years. At the time of the survey, 54% (269 of 500) of respondents were experiencing lesions affecting a BSA equivalent to at least three palms (3%). In response to questions on the burden of illness, 35% (176 of 500) of respondents indicated that they considered psoriasis to be a substantial problem in their daily life. Both affected BSA at the time of the survey and self-reported extent of skin involvement at the height of the condition (BSAmax) correlated with the perception of psoriasis as a substantial problem. Other subpopulations in which psoriasis was commonly identified as a substantial problem included women and individuals with diagnosed PsA. Whereas 18% (88 of 500) of respondents were diagnosed with PsA, the number who reported joint pain or stiffness was substantially higher (51%; 256 of 500), suggesting that some respondents may have had incipient or undiagnosed PsA. Conclusions: This survey reveals that psoriasis, PsA, and their associated comorbidities impose a severe burden on the daily lives of Canadians with a history of moderate to severe psoriasis.

scholarly journals Birt-Hogg-Dubé syndrome presenting with spontaneous pneumothorax and extensive pulmonary cysts in the absence of skin lesions or renal pathology

2019 ◽  
Vol 12 (9) ◽  
pp. e231039
Author(s):  
Kartik Kumar ◽  
Clare Ross
Keyword(s):  
Spontaneous Pneumothorax ◽  
Autosomal Dominant ◽  
Skin Lesions ◽  
Lung Cysts ◽  
Cystic Lung ◽  
Increased Risk ◽  
Renal Tumours ◽  
Pulmonary Cysts ◽  
Dominant Condition ◽  
Bhd Syndrome

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant condition which classically manifests with skin lesions such as fibrofolliculomas, pulmonary cysts that predispose to spontaneous pneumothorax and an increased risk of developing renal cell carcinoma. We describe the case of a patient who presented with a spontaneous pneumothorax on a background of multiple lung cysts, in the absence of cutaneous fibrofolliculomas and renal tumours. A germline mutation in the folliculin FLCN gene was subsequently identified, confirming BHD syndrome. Our case highlights the importance of considering a broad differential diagnosis for the cause of a spontaneous pneumothorax in the presence of unexplained cystic lung disease and emphasises the value of maintaining a high index of clinical suspicion for inherited causes of pneumothoraces.

scholarly journals The First Case Report of X-Linked Sideroblastic Anemia With Ataxia of Chinese Origin and Literature Review

2021 ◽  
Vol 9 ◽  
Author(s):  
Shiqiu Xiong ◽  
Yang Jia ◽  
Shijun Li ◽  
Peng Huang ◽  
Jie Xiong ◽  
...  
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Motor Development ◽  
Symptom Onset ◽  
Gene Mutations ◽  
Chinese Family ◽  
Inherited Disease ◽  
Sideroblastic Anemia ◽  
Chinese Origin ◽  
First Case

X-linked sideroblastic anemia with ataxia (XLSA/A) is a rare X-liked inherited disease, which was linked to the ABCB7 gene mutations. So far, five families have been reported worldwide. We present the first Chinese family of XLSA/A with novel ABCB7 gene mutation (c.2024A > G) and make a retrospective literature review. All affected patients were male. Age of symptom onset was <2 years old. The main symptoms included ataxia, delay in motor development, and mild sideroblastic anemia with obviously increased erythrocyte protoporphyrin. In this case, he had new symptoms that had not been reported in other cases such as epilepsy and cryptorchidism. We also discuss the possible molecular mechanism linking ABCB7 gene mutations to sideroblastic anemia and ataxia.

scholarly journals A systematic review assessing the existence of pneumothorax-only variants of FLCN. Implications for lifelong surveillance of renal tumours

2021 ◽  
Author(s):  
Kenki Matsumoto ◽  
Derek Lim ◽  
Paul D. Pharoah ◽  
Eamonn R. Maher ◽  
Stefan J. Marciniak
Keyword(s):  
Systematic Review ◽  
Skin Lesions ◽  
Confounding Factors ◽  
Lower Prevalence ◽  
Pathogenic Variants ◽  
Age Related ◽  
Pubmed Database ◽  
Renal Tumours ◽  
Pulmonary Cysts ◽  
Genetic Features

AbstractIndividuals with Birt–Hogg–Dubé syndrome (BHDS) may develop fibrofolliculomas, pneumothorax and/or renal cell carcinoma (RCC). Currently, all patients with pathogenic FLCN variants are recommended to have renal surveillance. It has however been suggested that some FLCN variants only cause pneumothorax, which would make surveillance unnecessary in certain cases. This review assesses this possibility. We provide an up-to-date analysis of clinical and genetic features of BHDS. The PUBMED database was systematically searched to find all articles describing patients with pathogenic FLCN variants. The relevant clinical and genetic features of these patients were recorded and analysed. The prevalence of pneumothorax, pulmonary cysts, RCC and characteristic skin lesions in BHDS were 50.9% (n = 1038), 91.9% (n = 720), 22.5% (n = 929) and 47.9% (n = 989), respectively. There was a higher prevalence of pneumothoraces (p < 0.0001) but lower prevalence of dermatological findings (p < 0.0001) in patients from East Asia compared to North America or Europe. Of the 194 pathogenic FLCN variants, 76 could be defined as ‘pneumothorax-only’. Pneumothorax only pathogenic variants (POPVs) were distributed throughout the gene, and there were no statistical differences in variant type. The majority of POPVs (65/76) affected no more than three individuals. Individuals with ‘POPVs’ also tended to be younger (45 vs. 47 years, p < 0.05). Many apparent POPVs in the literature could result from variable expressivity, age-related penetrance and other confounding factors. We therefore recommend that all individuals found to carry a pathogenic FLCN variant be enroled in lifelong surveillance for RCC.

scholarly journals  Erythema multiforme minor in a dog following inappropriate intranasal Bordetella bronchiseptica vaccination: a case report

2011 ◽  
Vol 56 (No. 11) ◽  
pp. 568-572 ◽  
Author(s):  
MH Kang ◽  
HM Park
Keyword(s):  
Case Report ◽  
Erythema Multiforme ◽  
Clinical Signs ◽  
Skin Lesions ◽  
Bordetella Bronchiseptica ◽  
Hydropic Degeneration ◽  
First Case ◽  
History Of ◽  
One Year

A one-year-old, intact female, Yorkshire terrier dog was presented with a six-month history of multifocal, polycyclic erythematous lesions with epidermal collarette formation at the axillae, the trunk and ventral abdomen. The dog had a history of an inappropriate vaccine administration one day prior to the onset of clinical signs. The histopathology of the lesions revealed apoptosis of keratinocytes in the overlying epidermis, hydropic degeneration and lymphocytic exocytosis. The clinical signs and histopathology of the lesions were compatible with erythema multiforme. The skin lesions resolved after treatment with prednisolone combined with azathioprine for one month. No recurrence of clinical signs occurred during the follow-up period (four months). This is the first case report of erythema multiforme associated with an accidental subcutaneous injection of a Bordetella bronchiseptica vaccine. &nbsp;

Iatrogenic Hyperadrenocorticism in 12 Cats

2006 ◽  
Vol 42 (6) ◽  
pp. 414-423 ◽  
Author(s):  
Yu-Hsin Lien ◽  
Hui-Pi Huang ◽  
Pen-Heng Chang
Keyword(s):  
Rare Condition ◽  
Skin Lesions ◽  
Term Treatment ◽  
Corticosteroid Withdrawal ◽  
Long Term Treatment ◽  
History Of ◽  
The Mean ◽  
Mean Time ◽  
Secondary Complication

Iatrogenic hyperadrenocorticism is an extremely rare condition in cats. Twelve cats with a medical history of progressive skin lesions and long-term treatment with corticosteroids were retrospectively studied. Noncutaneous signs in the cats were variable and included anorexia, lethargy, polydipsia, polyuria, and atrophy of the thigh muscles. Laboratory abnormalities included leukocytosis, elevated alanine aminotransferase levels, and hyperglycemia. Transient diabetes mellitus was a secondary complication in four cats, and transient hypothyroidism was suspected in four cats. The mean time for regression of signs was 4.9 months after corticosteroid withdrawal.

scholarly journals Change in a child’s naevus prompts referral to a dermatology service

2014 ◽  
Vol 6 (2) ◽  
pp. 123 ◽  
Author(s):  
Harriet Cheng ◽  
Amanda Oakley ◽  
Marius Rademaker
Keyword(s):  
Skin Lesions ◽  
Non Melanoma Skin Cancer ◽  
Specialist Referral ◽  
Spindle Cell Tumours ◽  
History Of ◽  
Melanocytic Naevi ◽  
The Mean ◽  
Sole Criterion ◽  
Referral Letters ◽  
Melanoma Skin

INTRODUCTION: Although melanoma is rare in children, parental concern about skin lesions often results in specialist referral and/or excision of benign lesions. AIM: To review dermatology referrals of children with skin lesions to determine reason for referral, macroscopic and dermatoscopic features of referred lesions, diagnosis, management and histology for excised lesions. METHODS: Referral letters, clinical and dermatoscopic images and outcomes were reviewed for skin lesions in children aged 0–18 years attending a teledermoscopy clinic over a 28-month period. RESULTS: Eighty-nine children with 128 lesions accounted for 9% of all referrals to the teledermoscopy clinic. The mean age of the children was 12 years (range 2–18 years). A ‘changing mole’ was the most common reason for referral (35 children; 39%), followed by ‘possible melanoma’ (19; 21%), and congenital naevus (9; 10%). The majority of lesions were benign melanocytic naevi (112 lesions; 88%). No lesions were diagnosed as melanoma or non-melanoma skin cancer. A history of change was given for 61/112 lesions (54%). Five lesions were excised; histopathological diagnoses were two spindle cell tumours of Reed, two compound naevi and one Spitz naevus. DISCUSSION: Change in a lesion, though a common trigger for referral, is less likely to indicate malignancy in children compared with adults and, as a sole criterion, does not necessitate specialist referral. Teledermoscopy clinics offer high quality macroscopic and dermatoscopic images and can assist in providing reassurance, where appropriate. KEYWORDS: Dermatology; dermoscopy; melanocytic naevi; melanoma

scholarly journals Familial Mediterranean Fever in Iran: A Report from FMF Registration Center

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Farhad Salehzadeh
Keyword(s):  
Abdominal Pain ◽  
Familial Mediterranean Fever ◽  
Mefv Gene ◽  
Positive Family History ◽  
Gene Mutations ◽  
Skin Lesions ◽  
Common Mutation ◽  
Clinical Criteria ◽  
Mediterranean Fever ◽  
The Mean

Background. Familial Mediterranean fever (FMF) is a periodic AR autoinflammatory disorder. This comprehensive study describes FMF in Iran as a country near Mediterranean area.Materials and Methods. From the country FMF registration center 403 patients according to Tel-Hashomer criteria enrolled this study, 239 patients had MEFV gene mutations analyses. Data, if needed, was analyzed by SPSS v20.Results. 175 patients (43.4%) were female and 228 patients (56.6%) were male. The mean age was 21.3 years. Abdominal pain was in 93.3% patients and 88.1% had fever. Abdominal pain was the main complaint of patients in (49.6%). The mean interval between attacks was36.5±29.6days and the mean duration of every episodes was43.3±34.5hours. 15.1% of patients had positive family history and 12.7% had previous surgery; in 52.3% of patients delay in diagnosis was more than three years. 12 common MEFV gene mutations were analyzed, 21.33% were without mutations, 39.7% had compound heterozygote, 25.52% showed heterozygous, and 13.38% showed homozygous results. The most common compound genotype was M694V-V726A (% 10.46) and in alleles M694V (% 20.9) and V726A (% 12.7) were the most frequent mutations, respectively.Conclusion. M694V was the most common mutation, and the most common compound genotype was M694V-V726A. Our genotype results are similar to Arabs and in some way to Armenians, erysipelas-like skin lesions are not common in this area, and clinical criteria are the preferred methods in diagnosis of FMF.

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