A Case Report Of BHD Syndrome And Literature Review

Objective: Combining the clinical data of a patient with BHD syndrome,the clinical characteristics of BHD syndrome were discussed to deepen the understanding of BHD syndrome.Methods: the symptoms,laboratory examination,imaging examination,pathological features,diagnosis and treatment of a case of BHD syndrome in our hospital were reported,and the relevant literatures at home and abroad were reviewed to discuss the characteristics and diagnosis and treatment of BHD syndrome.Results:(1)Case report: A 32-year-old male with a history of pneumothorax for6 times and bilateral pneumothorax.The main symptoms are cough,chest pain and shortness of breath.Family history of pneumothorax denied.No papules were found on examination.Renal ultrasound showed no space-occupying lesions or cysts.Chest CT scan suggests bilateral medial and basal bullae.Gene testing revealed FLCN gene mutation(exon 12 c.1429 c >T heterozygous mutation),while the mother and brother of the patient showed the same gene mutation.(2)Literature review results:A total of 828 cases of BHD syndrome at home and abroad were collected,ranging in age from 5 months to 90 years old.There was no difference in onset between men and women.The median age of onset of pneumothorax was 33 years old(26,43),the median age of onset of renal cancer was 49 years old(77±14),and the median age of onset of rash was 30 years old(21,40).Clinical symptoms included skin lesions of 50.2%(416/828),lung cysts of 48.3%(400/828),pneumothorax of 53.1%(440/828),kidney cancer of 17.3%(143/828).The lung cysts are mostly located in the basal part,and then in the subpleural part.They are mostly located in both lungs,and most of the size is within 5 cm.Only 35.3%(292/828)showed pulmonary cysts/pneumothorax,of which China accounted for 64.0%(112/175),Followed by Japan 55.2%(79/143)and Europe and America 16.0%(68/425).FLCN gene detection was performed at 89.0%(737/828),and the new FLCN mutation was 12.1%(89/737).There were a total of 175 cases in China,including 62.9% of pneumothorax(110/175),77.1% of pulmonary cyst(135/175),7.4% of renal carcinoma(13/175),21.1%of skin lesions(37/175),98.3% of FLCN gene detection(172/175),and 23.3%of new FLCN mutations(40/172).There were 143 cases in Japan,including pneumothorax 73.4%(105/143),lung cyst 68.5%(98/143),skin lesion 30.8%(44/143),kidney cancer 16.8%(24/143),FLCN gene test 93.7%(134/143),new FLCN mutation 5.2%(7/134).In Chinese and Japanese patients with BHDS,there was no significant statistical significance in the manifestations of pulmonary cyst and skin lesions(P >0.05),but there was significant statistical significance in the manifestations of renal carcinoma(P<0.05),and the new mutation of FLCN was statistically significant in both countries(P< 0.05).There were 425 patients in Europe and the United States,including 61.9%(263/425)of skin lesions,17.4%(74/425)of kidney cancer,33.2%(141/425)of lung cysts,and 41.9%(178/425)of pneumothorax.FLCN gene detection was performed at 85.4%(363/425),and new FLCN mutations were detected at 9.9%(36/363).The clinical manifestations and new FLCN gene mutations of BHDS patients in China and Europe and the United States were statistically significant(P < 0.05).This type of mutation has been reported only in the United States and Europe,and no missense mutations have been reported in the Japanese cases.There were differences in mutation composition ratio between China and Japan,Europe and America(P<0.05).The differences in deletion,nonsense and missense mutations between China and Japan were statistically significant(P<0.05),while the differences in insertion/deletion and missense mutations between China and European and American countries were statistically significant(P<0.05).A total of 491 families were reported,of which 10.4%(86/828)of asymptomatic patients were found in the connoisseur examination,and 40.1%(197/491)had a family history of lung cysts/pneumothorax.Conclusion:(1)Birt-Hogg-Dubé(BHD)syndrome is an autosomal dominant genetic disorder characterized by fibrofolliculomas of the skin,recurrent pneumothorax or multiple lung cysts and renal tumors.(2)The clinical features of BHDS in China are different from those in Japan,Europe and America.Pneumothorax/pulmonary cysts are the main presentation of BHDS patients in China,and may be the only or first symptom.Renal carcinoma and skin lesions are rare.(3)Imaging features are characterized by bilateral multiple pulmonary cysts at the base of the lung,which are helpful in differentiating it from other cystic lung diseases.(4)FLCN gene test is the basis of diagnosis.The genetic characteristics of BHDS in China are different from those in Japan,Europe and America.The correlation between genes and clinical characteristics needs further study.(5)FLCN gene testing is recommended for patients with a family history of recurrent pneumothorax/multiple pulmonary cysts suspected of BHDS,regardless of skin or kidney lesions.At the same time,all at-risk relatives of patients with BHDS should be recommended for genetic counseling,FLCN genetic testing,and kidney follow-up.