Birt-Hogg-Dubé Working Group, Department of Dermatology, VU University Medical Centre, Amsterdam, The Netherlands.
J Am Acad Dermatol. 2012 Feb;66(2):259.e1-9. doi: 10.1016/j.jaad.2010.11.039. Epub 2011 Jul 26.
Previously, we proposed that familial multiple trichodiscomas (OMIM 190340) is distinct from Birt-Hogg-Dubé syndrome (BHD) (OMIM #135150). BHD is characterized by multiple fibrofolliculomas/trichodiscomas, lung cysts, pneumothorax, and renal cell cancer. Germline FLCN mutations can be detected in most but not all BHD families.
We sought to evaluate familial multiple trichodiscomas at a clinical and genetic level. We now renamed this condition "familial multiple discoid fibromas" (FMDF) to emphasize the distinction from BHD.
In 8 additional families with an autosomal dominant pattern of multiple discoid fibromas we assessed the clinical findings and the histopathological features of skin lesions. FLCN germline mutation analysis was completed in 7 families. In two of these families segregation analysis was performed using polymorphic DNA markers in and around the FLCN locus.
The clinical findings in FMDF are different from those in BHD with early onset of skin lesions, prominent involvement of the pinnae, and discoid fibromas without the follicular epithelial component characteristic of the fibrofolliculoma/trichodiscoma spectrum of BHD. In addition, there were no evident pulmonary or renal complications. In none of the families were pathogenic FLCN germline mutations identified. Using segregation analysis we could exclude involvement of the FLCN locus in the two kindreds tested.
The prevalence of FMDF is presently unknown. The underlying gene defect has not yet been identified.
FMDF is clinically distinct from BHD and is not linked to the FLCN locus.
此前，我们提出家族性多发性毛发角化瘤（OMIM 190340）与 Birt-Hogg-Dubé 综合征（BHD）（OMIM #135150）不同。BHD 的特征是多发性纤维毛囊瘤/毛发角化瘤、肺囊肿、气胸和肾细胞癌。大多数但不是所有 BHD 家族都可以检测到种系 FLCN 突变。
我们旨在从临床和遗传水平评估家族性多发性毛发角化瘤。我们现在将这种情况重新命名为“家族性多发性盘状纤维瘤”（FMDF），以强调与 BHD 的区别。
在另外 8 个具有常染色体显性遗传模式的多发性盘状纤维瘤家族中，我们评估了皮肤病变的临床发现和组织病理学特征。在 7 个家族中完成了 FLCN 种系突变分析。在其中的两个家族中，使用 FLCN 基因座内和周围的多态性 DNA 标记进行了分离分析。
FMDF 的临床发现与 BHD 不同，其皮肤病变的发病年龄较早，耳廓受累明显，且盘状纤维瘤无滤泡上皮成分，这是 BHD 纤维毛囊瘤/毛发角化瘤谱的特征。此外，没有明显的肺部或肾脏并发症。在没有一个家族中发现致病性 FLCN 种系突变。使用分离分析，我们可以排除在两个测试的家族中涉及 FLCN 基因座。
目前尚不清楚 FMDF 的流行率。尚未确定潜在的基因缺陷。
FMDF 与 BHD 在临床上不同，与 FLCN 基因座无关。
