Abstract：
To report a rare case of Birt-Hogg-Dubé Syndrome (BHD) with progressive chorioretinopathy.
Case report.
A 55-year-old woman presented with longstanding nyctalopia attributed to a congenital retinal dystrophy, but no prior genetic testing. Her posterior pole examination demonstrated retinal pigment epithelium (RPE) mottling with extensive macular drusen and paracentral chorioretinal atrophy, consistent with a fleck retinopathy. Her past medical history was remarkable for nephrectomy for unilateral renal malignancy, parotid tumors and thyroid nodules. Dark adaptation time was prolonged, and electroretinography (ERG) revealed abnormal waveforms with depressed amplitudes. Genetic testing confirmed a deletion mutation in the folliculin (FLCN) gene and was negative for other relevant mutations, including EFEMP1 responsible for autosomal dominant macular and peripapillary drusen in Doyne honeycomb retinal dystrophy and TIMP3 responsible for Sorsby Fundus Dystrophy.
BHD is a rare autosomal-dominant disorder with multi-systemic clinical manifestations caused by a mutation in the FLCN gene. Affected individuals are prone to renal and pulmonary cysts, renal cancer, and fibrofolliculomas. Reports on ocular manifestations of BHD include eyelid fibrofolliculomas, flecked chorioretinopathy, choroidal melanoma, choroidal melanoma with sector melanocytosis, and retinal pigment epithelial micro-detachments. In this case of BHD, we note a fleck retinopathy with bilateral chorioretinal atrophy, displaying a phenotype of extensive chorioretinopathy associated with impaired dark adaptation and ERG abnormalities.
BHD: Birt-Hogg-Dubé syndrome; FLCN: Folliculin. RPE: retinal pigment epithelium; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye). OU: Oculus uterque (both eyes); ERG: electroretinogram; mfERG: multifocal electroretinography. ffERG: full-field electroretinography; FAF: fundus autofluorescence; OCT: optical coherence tomography; FA: fluorescein angiography; DA: dark-adapted; LA: light-adapted; mTOR: mammalian target of rapamycin; EFEMP1: epithelial growth factor-containing fibulin-like extracellular matrix protein 1; VPS13B: Vacuolar Protein Sorting 13 Homolog B; AGBL5: AATP/GTP-Binding Protein Like 5; ALMS1: Alstrom Syndrome 1; COL1BA1: Collagen Type I Beta, Alpha Chain 1; PDE6A: Rod Phosphodiesterase 6-alpha; USH2A: Usherin 2a; VCAN: Versican; RP: Retinitis pigmentosa; AR: Autosomal recessive.
Case report.
A 55-year-old woman presented with longstanding nyctalopia attributed to a congenital retinal dystrophy, but no prior genetic testing. Her posterior pole examination demonstrated retinal pigment epithelium (RPE) mottling with extensive macular drusen and paracentral chorioretinal atrophy, consistent with a fleck retinopathy. Her past medical history was remarkable for nephrectomy for unilateral renal malignancy, parotid tumors and thyroid nodules. Dark adaptation time was prolonged, and electroretinography (ERG) revealed abnormal waveforms with depressed amplitudes. Genetic testing confirmed a deletion mutation in the folliculin (FLCN) gene and was negative for other relevant mutations, including EFEMP1 responsible for autosomal dominant macular and peripapillary drusen in Doyne honeycomb retinal dystrophy and TIMP3 responsible for Sorsby Fundus Dystrophy.
BHD is a rare autosomal-dominant disorder with multi-systemic clinical manifestations caused by a mutation in the FLCN gene. Affected individuals are prone to renal and pulmonary cysts, renal cancer, and fibrofolliculomas. Reports on ocular manifestations of BHD include eyelid fibrofolliculomas, flecked chorioretinopathy, choroidal melanoma, choroidal melanoma with sector melanocytosis, and retinal pigment epithelial micro-detachments. In this case of BHD, we note a fleck retinopathy with bilateral chorioretinal atrophy, displaying a phenotype of extensive chorioretinopathy associated with impaired dark adaptation and ERG abnormalities.
BHD: Birt-Hogg-Dubé syndrome; FLCN: Folliculin. RPE: retinal pigment epithelium; OD: Oculus dexter (right eye); OS: Oculus sinister (left eye). OU: Oculus uterque (both eyes); ERG: electroretinogram; mfERG: multifocal electroretinography. ffERG: full-field electroretinography; FAF: fundus autofluorescence; OCT: optical coherence tomography; FA: fluorescein angiography; DA: dark-adapted; LA: light-adapted; mTOR: mammalian target of rapamycin; EFEMP1: epithelial growth factor-containing fibulin-like extracellular matrix protein 1; VPS13B: Vacuolar Protein Sorting 13 Homolog B; AGBL5: AATP/GTP-Binding Protein Like 5; ALMS1: Alstrom Syndrome 1; COL1BA1: Collagen Type I Beta, Alpha Chain 1; PDE6A: Rod Phosphodiesterase 6-alpha; USH2A: Usherin 2a; VCAN: Versican; RP: Retinitis pigmentosa; AR: Autosomal recessive.
摘要：
■报告一例罕见的Birt-Hogg-Dubé综合征（BHD）伴进行性脉络膜视网膜病变。
■病例报告。
■一名55岁的女性因先天性视网膜营养不良而长期出现夜盲症，但之前没有基因检测.她的后极检查显示视网膜色素上皮（RPE）斑点伴有广泛的黄斑玻璃疣和中央旁脉络膜视网膜萎缩，与斑点视网膜病变一致。她的既往病史是单侧肾脏恶性肿瘤的肾切除术，腮腺肿瘤和甲状腺结节。黑暗适应时间延长，和视网膜电图（ERG）显示异常波形，振幅降低。基因检测证实foliculin(FLCN)基因存在缺失突变,其他相关突变均为阴性,包括在Doyne蜂窝状视网膜营养不良中负责常染色体显性遗传性黄斑和乳头状玻璃疣的EFEMP1和负责Sorsby眼底营养不良的TIMP3。
■BHD是一种罕见的常染色体显性遗传病，由FLCN基因突变引起的多系统临床表现。受影响的个体容易出现肾和肺囊肿，肾癌,和纤维叶瘤。关于BHD的眼部表现的报告包括眼睑纤维囊瘤，斑点脉络膜视网膜病变,脉络膜黑色素瘤,脉络膜黑色素瘤伴有扇形黑素细胞增多，和视网膜色素上皮微脱离。在BHD的案例中,我们注意到伴有双侧脉络膜视网膜萎缩的斑点视网膜病变，显示与暗适应受损和ERG异常相关的广泛脉络膜视网膜病变的表型。
■BHD：Birt-Hogg-Dubé综合征；FLCN：Folliculin。RPE：视网膜色素上皮；OD：Oculusdexter（右眼）；OS：Oculussinister（左眼）。OU：Oculus子宫（双眼）；ERG：视网膜电图；mfERG：多焦视网膜电图。ffERG：全视野视网膜电图；FAF：眼底自发荧光；OCT：光学相干断层扫描；FA：荧光素血管造影术；DA：暗适应；LA：光适应；mTOR：哺乳动物雷帕霉素靶；EFEMP1：含上皮生长因子的腓骨蛋白样细胞外基质蛋白1；VPS13B：液泡蛋白分选13同系物B；AGBL5：AALTP-1，类胶原：Alα链1；PDE6A：杆磷酸二酯酶6-α；USH2A：Usherin2a；VCAN：Versican；RP：色素性视网膜炎；AR：常染色体隐性。
■病例报告。
■一名55岁的女性因先天性视网膜营养不良而长期出现夜盲症，但之前没有基因检测.她的后极检查显示视网膜色素上皮（RPE）斑点伴有广泛的黄斑玻璃疣和中央旁脉络膜视网膜萎缩，与斑点视网膜病变一致。她的既往病史是单侧肾脏恶性肿瘤的肾切除术，腮腺肿瘤和甲状腺结节。黑暗适应时间延长，和视网膜电图（ERG）显示异常波形，振幅降低。基因检测证实foliculin(FLCN)基因存在缺失突变,其他相关突变均为阴性,包括在Doyne蜂窝状视网膜营养不良中负责常染色体显性遗传性黄斑和乳头状玻璃疣的EFEMP1和负责Sorsby眼底营养不良的TIMP3。
■BHD是一种罕见的常染色体显性遗传病，由FLCN基因突变引起的多系统临床表现。受影响的个体容易出现肾和肺囊肿，肾癌,和纤维叶瘤。关于BHD的眼部表现的报告包括眼睑纤维囊瘤，斑点脉络膜视网膜病变,脉络膜黑色素瘤,脉络膜黑色素瘤伴有扇形黑素细胞增多，和视网膜色素上皮微脱离。在BHD的案例中,我们注意到伴有双侧脉络膜视网膜萎缩的斑点视网膜病变，显示与暗适应受损和ERG异常相关的广泛脉络膜视网膜病变的表型。
■BHD：Birt-Hogg-Dubé综合征；FLCN：Folliculin。RPE：视网膜色素上皮；OD：Oculusdexter（右眼）；OS：Oculussinister（左眼）。OU：Oculus子宫（双眼）；ERG：视网膜电图；mfERG：多焦视网膜电图。ffERG：全视野视网膜电图；FAF：眼底自发荧光；OCT：光学相干断层扫描；FA：荧光素血管造影术；DA：暗适应；LA：光适应；mTOR：哺乳动物雷帕霉素靶；EFEMP1：含上皮生长因子的腓骨蛋白样细胞外基质蛋白1；VPS13B：液泡蛋白分选13同系物B；AGBL5：AALTP-1，类胶原：Alα链1；PDE6A：杆磷酸二酯酶6-α；USH2A：Usherin2a；VCAN：Versican；RP：色素性视网膜炎；AR：常染色体隐性。
