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Birt-Hogg-Dube syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature.

ABSTRACT: BACKGROUND:Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis characterized by benign growth of the hair follicles, the presence of pulmonary cysts, spontaneous pneumothorax, and bilateral renal tumors that are usually hybrid oncocytic or multifocal chromophobe renal cell carcinoma. The diagnosis is confirmed by the presence of a pathogenic variant in the tumor suppressor folliculin (FLCN) gene mapped at 17p11.2. Although the dermatological lesions typical of BHDS are benign and only cause aesthetic concerns, and the pulmonary manifestations are controllable, the greater tendency of patients with this syndrome to present benign or malignant renal tumors, often bilateral and multifocal, makes the diagnosis of this syndrome important for the prognosis of the patients. The objective was to report the case of a patient with BHDS, without pulmonary manifestations and with hyperplastic polyposis of the gastrointestinal tract, and to perform a literature review. CASE PRESENTATION:A 60-year-old man complained of abdominal pain and diarrhoea for 2?months. Physical examination was normal except for the presence of normochromic papules in the frontal region of the face associated with hyperkeratotic and hyperchromic papules in the dorsal region. The excisional biopsies of the skin lesions indicated trichodiscomas. Esophagogastroduodenoscopy, enteroscopy, and colonoscopy showed the presence of hyperplastic polyps in the stomach, duodenum, jejunum, colon, and rectum. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen revealed multiple expansive solid lesions in both kidneys, with necrotic and calcified areas. Renal magnetic resonance angiography also showed a solid lesion in the right kidney measuring 5?cm in diameter and another solid lesion in the left kidney measuring 8?cm in diameter, both suggestive of renal angiomyolipoma. CT scans of the skull, chest, and temporal bones were normal. The genetic study revealed the presence of a variant of FLCN in the intron 13. CONCLUSIONS:To the best of our knowledge, this is the first reported case of BHDS with the simultaneous finding of gastrointestinal hyperplastic polyposis, which may represent a possible phenotypic expression of this syndrome that has not yet been described.

SUBMITTER: Balsamo F

PROVIDER: S-EPMC7071710 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Birt-Hogg-Dubé syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature.

Balsamo Flávia F Cardoso Pedro Augusto Soffner PAS do Amaral Junior Sergio Aparecido SA Theodoro Therésè Rachell TR de Sousa Gehrke Flavia F da Silva Pinhal Maria Aparecida MA Bianco Bianca B Waisberg Jaques J

BMC medical genetics 20200314 1

<h4>Background</h4>Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant genodermatosis characterized by benign growth of the hair follicles, the presence of pulmonary cysts, spontaneous pneumothorax, and bilateral renal tumors that are usually hybrid oncocytic or multifocal chromophobe renal cell carcinoma. The diagnosis is confirmed by the presence of a pathogenic variant in the tumor suppressor folliculin (FLCN) gene mapped at 17p11.2. Although the dermatological lesions typical of BHDS ...[more]

PMID: 32171268

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Project description:ObjectiveTo clarify the epidemiological and clinical features of Birt-Hogg-Dubé syndrome (BHDS) in Chinese patients.MethodsWe identified reports on Chinese patients with BHDS by searching the China Academic Journals Database, Wanfang Chinese Database, and PubMed databases, either in Chinese or English languages published from January 1, 2008 to December 31, 2020. Studies without sufficient clinical data were excluded and cases under 18 years old were excluded.ResultsTwenty papers were included and comprised 120 families with 221 cases. Most families with BHDS were reported from institutions in Beijing (66.7%) and Jiangsu Province (15.8%); 80.8% of cases were reported within the past five years. The average duration from clinical presentation to diagnosis was 9.6 years. The average age was 47.0 ± 13.9 years (range, 18-84 years) and the ratio of male to female was 1:1.6. The most common manifestations of BHDS were multiple pulmonary cysts (92.4%), spontaneous pneumothorax (71.0%), skin lesions (18.1%) and renal tumors (3.6%). Pulmonary cysts were predominantly distributed in the lower lobe on chest CT imaging. Family history of spontaneous pneumothorax was identified in 84.7% of the families and average number of pneumothoraxes was 1.8 (range, 1-6). The FLCN gene mutation c.1285dupC/delC in exon 11 was the most frequent mutation observed (17.4% of patients). The recurrence rate of pneumothorax after conservative treatment (including tube thoracostomy) was 29/41 (71%) while the pneumothorax recurred after surgical treatment (pulmonary bullectomy or pleurodesis) in only 4/37 (11%).ConclusionsAlthough BHDS has been increasingly reported in the recent years, only minority of families were reported from institutions outside of Beijing and Jiangsu Province. The dominant clinical manifestations were pulmonary cysts associated with recurrent pneumothorax, while skin lesions and renal tumors were less commonly reported. Delayed diagnosis along with suboptimal management appear to represent critical challenges for Chinese patients with BHDS.

Project description:RationaleSpontaneous pneumothorax is a common complication of Birt-Hogg-Dubé syndrome (BHD).ObjectivesThe optimal approach to treatment and prevention of BHD-associated spontaneous pneumothorax, and to advising patients with BHD regarding risk of pneumothorax associated with air travel, is not well established.MethodsPatients with BHD were recruited from the Rare Lung Diseases Clinic Network and the BHD Foundation and surveyed about disease manifestations and air travel experiences.ResultsA total of 104 patients completed the survey. The average age at diagnosis was 47 years, with an average delay from first symptoms of 13 years. Pulmonary cysts were the most frequent phenotypic manifestation of BHD, present in 85% of patients. Spontaneous pneumothorax was the presenting manifestation that led to the diagnosis of BHD in 65% of patients, typically after the second episode (mean, 2.4 episodes). Seventy-nine (76%) of 104 patients had at least one spontaneous pneumothorax during their lifetime, and 82% had multiple pneumothoraces. Among patients with multiple pneumothoraces, 73% had an ipsilateral recurrence, and 48% had a subsequent contralateral spontaneous pneumothorax following a sentinel event. The mean ages at first and second pneumothoraces were 36.5 years (range, 14-63 yr) and 37 years (range, 20-55 yr), respectively. The average number of spontaneous pneumothoraces experienced by patients with a sentinel pneumothorax was 3.6. Pleurodesis was generally performed after the second (mean, 2.4) ipsilateral pneumothorax and reduced the ipsilateral recurrence rate by half. A total of 11 episodes of spontaneous pneumothorax occurred among eight patients either during or within the 24-hour period following air travel, consistent with an air travel-related pneumothorax rate of 8% per patient and 0.12% per flight. Prior pleurodesis reduced the occurrence of a subsequent flight-related pneumothorax.ConclusionsSpontaneous pneumothorax is an important, recurrent manifestation of pulmonary involvement in patients with BHD, and pleurodesis should be considered following the initial pneumothorax to reduce the risk of recurrent episodes. In general, in patients with BHD, pneumothorax occurs in about 1-2 per 1,000 flights, and the risk is lower among patients with a history of prior pleurodesis.

Project description:Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant cancer syndrome characterised by benign skin tumours, renal tumours, and spontaneous pneumothorax. The gene has been mapped to chromosome 17p11.2 and recently identified, expressing a novel protein called folliculin. We report the clinical and genetic studies of four sporadic BHD cases and four families with a total of 23 affected subjects. Haplotype analysis of these families using BHD linked markers showed they did not share the same affected alleles, excluding common ancestry. Mutation analysis of the BHD gene identified two germline mutations on exon 11 (c.1733insC and c.1733delC) in three of four families as well as two of four sporadic cases. A novel somatic mutation, c.1732delTCinsAC, was detected in a BHD related chromophobe renal carcinoma. Our results confirmed the (C)8 tract in exon 11 as a mutational hot spot in BHD and should always be considered for future genetic testing. Our observation also indicated that the second hit (of Knudson's two hit theory) in some BHD related tumours is in the form of somatic mutation rather than LOH. In a large French family in which eight affected subjects carry the c.1733delC mutation, a phenocopy who has multiple episodes of spontaneous pneumothorax was identified. A total of five mutation carriers (aged between 37 to 66) did not have any evidence of BHD features, suggesting either reduced penetrance or late age of onset of the disease. In addition, six out of eight affected subjects who have positive germline mutation have confirmed neoplastic colonic polyps, indicating that colorectal neoplasia is an associated feature of BHD in some families. Our studies have observed several interesting genetic features in BHD: (1) the poly (C) tract in exon 11 as a mutational hot spot; (2) the existence of phenocopy; (3) reduced penetrance or late age of onset of disease; (4) association with colorectal neoplasia in some families; and (5) somatic mutation instead of LOH as the second hit in BHD tumours.

Dataset Information

Birt-Hogg-Dube syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature.

Publications

Birt-Hogg-Dubé syndrome with simultaneous hyperplastic polyposis of the gastrointestinal tract: case report and review of the literature.

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