To date, there have been no prospective studies attempting to diagnose BHD syndrome or literature reviews on BHD in Korea. Park et al. (2017) address this in their new study that aims to detect BHD prospectively in patients undergoing chest computed tomography (CT) scans and to classify the characteristics of BHD in Korea.
The authors reviewed the chest CT scans obtained from 10,883 patients from Korea. Eighteen of these patients were suspected of BHD and seventeen underwent screening for FLCN mutation. Six were confirmed to have BHD by FLCN gene test. These patients were classified into a BHD group (n=6) and the remaining (negative for FLCN mutation) into a non-BHD group (n=11). Spontaneous pneumothorax tended to be more frequent in the BHD group than in the non-BHD group. The prevalence of kidney and skin lesions was not significantly different between the groups. None of the patients had a family history of kidney or skin BHD symptoms.
The maximum size of the pulmonary cysts observed on chest CT in the BHD group was significantly larger than that in the non-BHD group. In addition, unlike the non-BHD patients, all the patients in the BHD group had cysts with variable morphology. One third of patients with BHD had multiseptated cysts but no cysts of this type were found in the non-BHD group. However, there was no significant difference in the number of cysts and their location, and costophrenic angle (CPA) involvement between the two groups.
In the BHD group, typical skin and kidney lesions were not observed in any patients. However, some atypical lesions were found. Within the four patients who underwent a skin examination, a fibroma was found on the nose of one patient. Within the four patients with renal imaging available, one had multiple renal cysts, and one clear cell-type renal cell carcinoma (RCC). All patients had normal lung function.
The authors then analysed a total of twelve Korean patients with BHD: six diagnosed in the present study (Patients 1–6), plus six previously diagnosed with BHD in the literature (Patients 7–12). The male to female ratio was 5:7, and the mean age was 50 years. Nine patients had a history of pneumothorax. None of the nine patients who underwent renal imaging had typical lesions, although atypical renal cyst or clear cell RCC was present in three patients. Two of the ten patients who underwent skin examination had typical skin lesions and three had atypical lesions (fibromas or papules with lymphocyte infiltration). Patient three had lung adenocarcinoma, however, lung pathology related to BHD was not found.
The most frequently observed FLCN mutations were c.1285dupC in four patients with two of them presenting typical skin lesions followed by c.1557delT. Patients 11 and 12 were related to patient 10 and the same mutation, c.882_884delTTC. In addition, c.1215C>G and c.1285delC mutations were each detected in one patient. There was no relationship between genotype and phenotype.
The prevalence and incidence of BHD in this study could not be determined because at least 2 years are needed to define this, the research was conducted at a single institution, and the patients were not representative of the general population.
BHD is considered to be the cause in 5–10% of spontaneous pneumothorax cases (Johannesma et al., 2015). However, the present study included patients with BHD who did not have pneumothorax history (50%). Therefore, careful review of the chest CT scans of patients with pulmonary cysts, even in patients without pneumothorax, might be helpful in identifying patients with BHD and their family members and radiologists should be aware of this.
Typical skin lesions are observed in ~90% of patients with BHD in the USA and Europe, but less frequently in Asia (Murakami et al., 2014; Toro et al., 2008; Furuya et al., 2013). This study found typical skin lesions in only 20% of Korean cases. In addition, the authors did not identify typical renal lesions in the Korean cases. In the USA and Europe, typical renal lesions are present in 15–35% of patients with BHD, but less frequently in Asia (Ding et al., 2015). In the USA and Europe, spontaneous pneumothorax has been reported to occur in 24–41% of cases (Skolnik et al., 2016; Toro et al., 2007), but has been reported in 68% of cases in China (Ding et al., 2015), in accordance with the also high prevalence of spontaneous pneumothorax (75%) in this study. However, it is important to address that the detection rate of skin, renal lesions and pneumothorax depends on the design of the study.
The small number of patients with BHD in the study does not allow reaching conclusions regarding demographic differences. Therefore, further studies comparing the prevalence of BHD symptoms according to nationality are needed.
- Park HJ, Park CH, Lee SE, Lee GD, Byun MK, Lee S, Lee KA, Kim TH, Kim SH, Yang SY, Kim HJ, & Ahn CM (2017). Birt-Hogg-Dube syndrome prospectively detected by review of chest computed tomography scans. PloS one, 12 (2) PMID: 28151982