Letter to the Editor
A case of Birt–Hogg–Dubé syndrome
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Morais-Almeida, H. Pité, A.M. Pereira, M. Ferreira-Magalhães, J.A. Fonseca" "autores" => array:5 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Morais-Almeida" ] 1 => array:2 [ "nombre" => "H." "apellidos" => "Pité" ] 2 => array:2 [ "nombre" => "A.M." "apellidos" => "Pereira" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Ferreira-Magalhães" ] 4 => array:2 [ "nombre" => "J.A." "apellidos" => "Fonseca" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511516300628?idApp=UINPBA00004E" "url" => "/21735115/0000002200000006/v1_201612110145/S2173511516300628/v1_201612110145/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "A case of Birt–Hogg–Dubé syndrome" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "365" "paginaFinal" => "366" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "L. Martins, M. Caixeiro, C. Costa, S. Feijó, C. Bárbara" "autores" => array:5 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Martins" "email" => array:1 [ 0 => "lfpm84@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Caixeiro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Costa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "S." "apellidos" => "Feijó" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "C." "apellidos" => "Bárbara" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Pulmonary Medicine, Centro Hospitalar Lisboa Norte, Lisboa, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Infectious Diseases, Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 571 "Ancho" => 1500 "Tamanyo" => 103242 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Thoracoscopy shows cluster of cysts in the left superior lobe and (b) chest-CT shows multiple lung cysts with various size and irregular shape.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Birt–Hogg–Dubé syndrome (BHDS) or Hornstein–Knickenberg syndrome, is a rare autosomal dominant disorder, clinically characterized by skin fibrofolliculomas, pulmonary cysts, which can lead to spontaneous pneumothorax, and renal malignancy.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This condition is caused by germline mutations in the tumor suppressor gene folliculin (FCLN) (OMIM#135150), located in the short arm of chromosome 17 (17p11.2).<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The clinical manifestations are widely variable which may account for BHDS being underdiagnosed.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We present a case of a never-smoking, 57-year-old male, presented to the emergency department with a 3-week history of dyspnea and dry cough. His past medical history included a left spontaneous pneumothorax 20 years ago, which was conservatively managed, hypertension and chronic atrial fibrillation. On examination his chest revealed hyper-resonance and reduced breath sounds over the left lung. Chest X-ray showed a left-sided pneumothorax with complete lung collapse. Since it was his second episode, chest drainage was performed, followed by thoracoscopic pleurodesis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a). His chest-CT showed multiple bilateral sharply marginated pulmonary cysts (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b). No subdiaphragmatic abnormalities were identified. On further clinical examination, our patient was noted to have pale, flat macules over his face, neck and upper trunk, for at least 20 years. There was also a family history of similar skin lesions affecting his mother. The presence of these skin lesions together with recurrent pneumothorax was suggestive of BHDS, which was further confirmed by genetic testing. This revealed a pathogenic frameshift c.573_574delinsT (p.Lys192Argfs*31) mutation in heterozygosity on exon 6 of the FCLN gene, previously described by Lencastre et al.,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> which confirms the diagnosis of BHDS.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">This syndrome was first described in 1977 by Birt, Hogg and Dubé in a Canadian family in which several members had skin lesions consisting of fibrofolliculomas with trichodiscomas and acrochordons.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2</span></a> More than 20 years later, the gene locus was mapped to chromosome 17p11.2.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1–5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Nowadays, pathogenic FCLN mutations have been described in more than 200 families worldwide.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,3</span></a> FCLN is a tumor suppressor gene<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> expressed in many tissues like skin, type-1 pneumocytes in the lungs and distal nephron in the kidneys.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Cutaneous fibrofolliculoma is the most frequent clinical manifestation and consists of multiple, asymptomatic, dome-shaped pale whitish papules with 2–4<span class="elsevierStyleHsp" style=""></span>mm diameters located primarily in the face, neck and upper torso.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1–3</span></a> Lesions develop after 25 years in 82–92% of the affected individuals.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> The most feared complication of BHDS is renal cancer. There is a sevenfold increased risk of renal cancer compared to the general population.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,3</span></a> Lung cysts and recurrent pneumothorax can be the earliest and only manifestations of BHDS.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> Lung cysts have been described in 77–89% of BHDS affected individuals. Pulmonary function tests are usually normal despite the presence of multiple lung cysts.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">BHDS lung cysts are distinct from bullae and blebs. The characteristic chest CT findings are multiple lung cysts of various sizes with an irregular shape and thin wall, commonly located in the lower medial and subpleural regions of the lung.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> The pneumothorax incidence in these patients has been estimated to be 33–38%,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> that is a 50-fold increased risk compared to unaffected individuals.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1–3</span></a> Recently, Johannesma et al. stated that probably 5–10% of (apparentely) primary spontaneous pneumothorax are caused by BHDS.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">We established our patient's diagnosis according to the criteria proposed by Menko et al. which include BHDS clinical manifestations and positive DNA testing result.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">If genetic testing is positive, family members should be referred for genetic counseling and FCLN sequencing.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Whenever BHDS is suspected, chest CT is recommended to identify lung cysts or the presence of pneumothorax.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> As pneumothorax recurrence rate is high, treatment differs from the one recommended for primary spontaneous pneumothorax, and according to some authors pleurodesis should be considered as the first line treatment option.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pneumococcal</span> and annual <span class="elsevierStyleItalic">influenza</span> vaccination are recommended, as well as periodic pulmonary function testing if abnormal lung function is noticed.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Family members at risk of BHDS should start renal tumor screening with MRI when reaching the age of 21 years, and preferably every 3 years thereafter. Once a renal mass is detected, screening should become annual until the mass has 3<span class="elsevierStyleHsp" style=""></span>cm in diameter, surgery being recommended afterwards.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Cutaneous lesions in BHDS are asymptomatic and hence treatment is offered for psychological and cosmetic reasons only.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">This is to our knowledge the second reported case of BHDS in Portugal. Our aim is to alert to its existence in order to allow for early detection and prevention of the more serious complications, such as renal cancer, both in presenting patients and in relatives at-risk.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 571 "Ancho" => 1500 "Tamanyo" => 103242 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(a) Thoracoscopy shows cluster of cysts in the left superior lobe and (b) chest-CT shows multiple lung cysts with various size and irregular shape.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Birt–Hogg–Dubé syndrome: diagnosis and management" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.H. 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Smit" 5 => "R.J. van Moorselaar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.00196914" "Revista" => array:7 [ "tituloSerie" => "Eur Respir J" "fecha" => "2015" "volumen" => "45" "numero" => "4" "paginaInicial" => "1191" "paginaFinal" => "1194" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25537564" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735115/0000002200000006/v1_201612110145/S2173511516300239/v1_201612110145/en/main.assets" "Apartado" => array:4 [ "identificador" => "20584" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735115/0000002200000006/v1_201612110145/S2173511516300239/v1_201612110145/en/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511516300239?idApp=UINPBA00004E" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 10 | 9 | 19 |
| 2024 October | 35 | 32 | 67 |
| 2024 September | 42 | 21 | 63 |
| 2024 August | 39 | 29 | 68 |
| 2024 July | 36 | 40 | 76 |
| 2024 June | 40 | 33 | 73 |
| 2024 May | 38 | 38 | 76 |
| 2024 April | 44 | 25 | 69 |
| 2024 March | 36 | 18 | 54 |
| 2024 February | 29 | 29 | 58 |
| 2024 January | 34 | 27 | 61 |
| 2023 December | 48 | 19 | 67 |
| 2023 November | 36 | 32 | 68 |
| 2023 October | 19 | 30 | 49 |
| 2023 September | 31 | 33 | 64 |
| 2023 August | 25 | 13 | 38 |
| 2023 July | 32 | 29 | 61 |
| 2023 June | 24 | 13 | 37 |
| 2023 May | 37 | 20 | 57 |
| 2023 April | 21 | 11 | 32 |
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