Birt-Hogg-Dubé syndrome: A case report

Margallo Iribarnegaray, Juan; Revuelta Salgado, Fernando; Martínez Martínez, María Teresa

doi:10.1016/j.medcle.2020.02.013

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He worked as a maintenance manager, without exposure to pulmonary toxins, and did not report contact with animals. He claimed to have consumed about 200g of alcohol per week until a year ago, having been abstinent since then. No smoking or consumption of other street drugs.His personal history included hypertension, OSAS treated with CPAP, alcoholic liver disease and multiple skin lesions that appeared 10 years earlier in the form of brownish papules and scars distributed over the face, abdomen, and anterior thoracic region, with no clear diagnosis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a). Among his family history, his mother had been diagnosed with “kidney cysts”, without study or follow-up.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>At the follow-up visits to the gastroenterology department, an abdominal CT scan showed bilateral solid renal lesions, three in the right kidney, the largest measuring 31mm, and one in the left kidney measuring 23mm, suspicious of malignancy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b). Lung sections showed cystic lung lesions in the middle lobe, lingula and both lower lobes, most of them subcentimetric (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>c).For this reason, he was admitted to hospital 9 months before he was referred to our clinic, performing a CT-guided biopsy of the right kidney, with the anatomical pathology diagnosis of oncocytoma of trabecular morphology. Radiological follow-up was decided, and he was referred to our clinic for lung cysts evaluation.Given the presence of renal lesions, multiple skin papules and lung cysts, a suspected diagnosis of Birt-Hogg-Dubé syndrome (BHD) was established. A study of the FLCN gene was requested, identifying a germline variant c.754dupG, p.A252Gfs*40, considered pathogenic and associated with BHD syndrome.Respiratory function tests were normal except for mild diffusion impairment (DLCO 63%), and a chest CT confirmed the presence of multiple bilateral lung cysts, predominantly in the lower lobes.The patient underwent clinical and radiological follow-up by chest-abdominal CT, with no new symptoms or progression of the lesions. A genetic study for BHD syndrome was recommended to his immediate family members.A lung cyst is a lesion defined as an area of lucency, of round morphology, delimited by a thin wall of less than 2mm thick and with a well-defined air/lung interface. Diffuse cystic lung diseases (DCLD) are a rare and heterogeneous group of diseases characterized by the presence of multiple cysts that affect all the lung lobes.<a class="elsevierStyleCrossRef" href="#bib0030">1</a>Within the differential diagnosis of DCLD we must consider entities such as lymphangioleiomyomatosis, Langerhans cell histiocytosis, lymphoid interstitial pneumonia, amyloidosis, and BHD syndrome. Other less common causes of CIDD include infections, neoplasms, light chain deposition disease and others.<a class="elsevierStyleCrossRefs" href="#bib0035">2,3</a>BHD syndrome is an autosomal dominant genetic disease caused by a mutation in the FCLN gene located on chromosome 17p11.2 which encodes folliculin. The disease is characterized by involvement of the skin, kidney and lung.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>Skin involvement is associated with the appearance of multiple papular lesions typically affecting the face, neck, and trunk. Histologically, they correlate with benign tumours.From a nephrological point of view, the BHD syndrome has been associated with the occurrence of kidney tumours between the ages of 25 and 75, which are usually bilateral and multifocal. Regarding anatomical pathology, they are very heterogeneous neoplasms, with the hybrid oncocytoma being the most common type.Finally, in the lung, the disease is associated with the development of multiple bilateral cysts in most cases. Around 25% of patients have a pneumothorax during the course of the disease, secondary to the rupture of one of these cysts.In terms of follow-up and clinical management, nephrology is where the main complexity of these patients resides due to the risk of developing malignancies. In general, radiological screening and surgical intervention is recommended when the largest tumour reaches 3cm.<a class="elsevierStyleCrossRef" href="#bib0050">5</a>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Margallo Iribarnegaray J, Revuelta Salgado F, Martínez Martínez MT. Síndrome de Birt-Hogg-Dubé: descripción de un caso. Med Clin (Barc). 2021;156:529–530." ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1089 "Ancho" => 1500 "Tamanyo" => 212223 ] ] "descripcion" => array:1 [ "en" => "(a) Papule located in the right malar region; (b) 31mm solid cortical renal neoplasm located in the upper pole of the right kidney; (c) Lung cysts in the middle lobe and lingula." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diffuse cystic lung diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Ryu" 1 => "X. Tian" 2 => "M. Baqir" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11684-013-0269-z" "Revista" => array:6 [ "tituloSerie" => "Front Med" "fecha" => "2013" "volumen" => "7" "paginaInicial" => "316" "paginaFinal" => "327" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23666611" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diffuse cystic lung disease. Part I" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Gupta" 1 => "R. Vassallo" 2 => "K.A. Wikenheiser-Brokamp" 3 => "F.X. 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McCormack" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201411-2096CI" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2015" "volumen" => "192" "paginaInicial" => "17" "paginaFinal" => "29" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25906201" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Birt-Hogg-Dube syndrome: diagnosis and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.H. Menko" 1 => "M.A. van Steensel" 2 => "S. Giraud" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(09)70188-3" "Revista" => array:6 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2009" "volumen" => "10" "paginaInicial" => "1199" "paginaFinal" => "1206" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19959076" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and management of BHD-associated kidney cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. Stamatakis" 1 => "A.R. Metwalli" 2 => "L.A. Middelton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10689-013-9657-4" "Revista" => array:6 [ "tituloSerie" => "Fam Cancer" "fecha" => "2013" "volumen" => "12" "paginaInicial" => "397" "paginaFinal" => "402" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23703644" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015600000010/v1_202105151030/S2387020621001996/v1_202105151030/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015600000010/v1_202105151030/S2387020621001996/v1_202105151030/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621001996?idApp=UINPBA00004N"]

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Vol. 156. Issue 10.

Pages 529-530 (May 2021)

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