Abstract：
To report the concurrent presentation and management of IQCB1-associated Leber Congenital Amaurosis and NDP-associated Familial Exudative Vitreoretinopathy (FEVR).
A 6-month-old Caucasian infant presented with poor visual response, high hypermetropia, and infantile-nystagmus with a provisional diagnosis of Leber Congenital Amaurosis based on clinical findings. Genetic counseling and testing were performed with a 285 gene retinal dystrophy panel (Blueprint Genetics). Clinical characteristics, presentation, ancillary testing results, and management are described.
Two previously reported heterozygous pathogenic variants in ICQB1 were identified (c.1518_1519del (p.His506Glnfs*13) and c.1381C>T, p.Arg461*) segregating in trans. In addition, a variation of uncertain significance (VUS) was found in NDP (c.280C>T; p.His94Tyr). Fluorescein angiography was performed demonstrating peripheral avascularity and retinal telangiectasia without frank neovascularization. Peripheral ablative laser was applied to the avascular zone.
The NDP VUS likely represents a pathogenic variant given the FEVR phenotype in addition to retinal degeneration, creating a rare dual phenotype. The combination of low oxygen demand from the IQCB1-associated retinal degeneration and NDP variant may have led to a more attenuated FEVR presentation with uncertain prognosis. A molecular diagnosis informed ocular and renal surveillance, as well as the recurrence risk for future offspring.
A 6-month-old Caucasian infant presented with poor visual response, high hypermetropia, and infantile-nystagmus with a provisional diagnosis of Leber Congenital Amaurosis based on clinical findings. Genetic counseling and testing were performed with a 285 gene retinal dystrophy panel (Blueprint Genetics). Clinical characteristics, presentation, ancillary testing results, and management are described.
Two previously reported heterozygous pathogenic variants in ICQB1 were identified (c.1518_1519del (p.His506Glnfs*13) and c.1381C>T, p.Arg461*) segregating in trans. In addition, a variation of uncertain significance (VUS) was found in NDP (c.280C>T; p.His94Tyr). Fluorescein angiography was performed demonstrating peripheral avascularity and retinal telangiectasia without frank neovascularization. Peripheral ablative laser was applied to the avascular zone.
The NDP VUS likely represents a pathogenic variant given the FEVR phenotype in addition to retinal degeneration, creating a rare dual phenotype. The combination of low oxygen demand from the IQCB1-associated retinal degeneration and NDP variant may have led to a more attenuated FEVR presentation with uncertain prognosis. A molecular diagnosis informed ocular and renal surveillance, as well as the recurrence risk for future offspring.
摘要：
报告IQCB1相关的Leber先天性黑蒙和NDP相关的家族性渗出性玻璃体视网膜病变（FEVR）的并发表现和管理。
一名6个月大的白种人婴儿视觉反应不佳，高远视眼,和婴儿眼球震颤，根据临床发现暂时诊断为Leber先天性黑蒙。使用285基因视网膜营养不良面板（蓝图遗传学）进行遗传咨询和测试。临床特征,介绍,辅助测试结果，和管理进行了描述。
在ICQB1中鉴定出两个先前报道的杂合致病变体（c.1518_1519del（p。His506Glnfs*13）和c.1381C>T，p.Arg461*）反式分离。此外,在NDP中发现了不确定显著性(VUS)的变化(c.280C>T;p.His94Tyr)。进行荧光素血管造影术，显示外周血管无血管化和视网膜毛细血管扩张，无明显的新生血管形成。外周消融激光应用于无血管区。
除了视网膜变性外，考虑到FEVR表型，NDPVUS可能代表一种致病变异，创造了一种罕见的双重表型。IQCB1相关的视网膜变性和NDP变异的低氧需求的组合可能导致更减弱的FEVR表现，预后不确定。分子诊断告知眼部和肾脏监测，以及未来后代的复发风险。
一名6个月大的白种人婴儿视觉反应不佳，
在ICQB1中鉴定出两个先前报道的杂合致病变体（c.1518_1519del（p。
除了视网膜变性外，考虑到FEVR表型，NDPVUS可能代表一种致病变异，
