Abstract：
OBJECTIVE: To report clinical and genetic characteristics of familial exudative vitreoretinopathy (FEVR) in the Finnish population.
METHODS: Detailed clinical and genetic data of 35 individuals with heterozygous pathogenic variants in FZD4 were gathered and analysed.
RESULTS: Thirty-two individuals with FZD4 c.313A>G variant and three individuals with FZD4 c.40_49del were included in the study. The clinical phenotype was variable even among family members with the same FZD4 variant. Only 34% (N = 12/35) of variant-positive individuals had been clinically diagnosed with FEVR. The median age of the onset of symptoms was 2.3 years, ranging between 0 to 25 years. Median visual acuity was 0.1 logMAR (0.8 Snellen decimal), ranging between light perception and -0.1 logMAR (1.25 Snellen decimal). Most (N = 33/35, 94%) were classified as not visually impaired. Despite unilateral visual loss present in some, they did not meet the criteria of visual impairment according to the WHO classification. Two study patients (N = 2/35, 6%) had severe visual impairment. The most common FEVR stage in study patient\'s eyes (N = 28/70 eyes, 40%) was FEVR stage 1, that is, avascular periphery or abnormal vascularisation. Most of FZD4-variant-positive study patient\'s eyes (N = 31/50 eyes, 62%) were myopic. Two individuals presented with persistent hyperplastic primary vitreous expanding the phenotypic spectrum of FEVR. Shared haplotypes extending approximately 0.9 Mb around the recurrent FZD4 c.313A>G variant were identified.
CONCLUSIONS: Most study patients were unaffected or had mild clinical manifestations by FEVR. Myopia seemed to be overly common in FZD4-variant-positive individuals.
METHODS: Detailed clinical and genetic data of 35 individuals with heterozygous pathogenic variants in FZD4 were gathered and analysed.
RESULTS: Thirty-two individuals with FZD4 c.313A>G variant and three individuals with FZD4 c.40_49del were included in the study. The clinical phenotype was variable even among family members with the same FZD4 variant. Only 34% (N = 12/35) of variant-positive individuals had been clinically diagnosed with FEVR. The median age of the onset of symptoms was 2.3 years, ranging between 0 to 25 years. Median visual acuity was 0.1 logMAR (0.8 Snellen decimal), ranging between light perception and -0.1 logMAR (1.25 Snellen decimal). Most (N = 33/35, 94%) were classified as not visually impaired. Despite unilateral visual loss present in some, they did not meet the criteria of visual impairment according to the WHO classification. Two study patients (N = 2/35, 6%) had severe visual impairment. The most common FEVR stage in study patient\'s eyes (N = 28/70 eyes, 40%) was FEVR stage 1, that is, avascular periphery or abnormal vascularisation. Most of FZD4-variant-positive study patient\'s eyes (N = 31/50 eyes, 62%) were myopic. Two individuals presented with persistent hyperplastic primary vitreous expanding the phenotypic spectrum of FEVR. Shared haplotypes extending approximately 0.9 Mb around the recurrent FZD4 c.313A>G variant were identified.
CONCLUSIONS: Most study patients were unaffected or had mild clinical manifestations by FEVR. Myopia seemed to be overly common in FZD4-variant-positive individuals.
摘要：
目的：报告芬兰人群家族性渗出性玻璃体视网膜病变（FEVR）的临床和遗传特征。
方法：收集并分析了35例FZD4杂合致病变异个体的详细临床和遗传数据。
结果：32名具有FZD4c.31A>G变体的个体和3名具有FZD4c.40_49del的个体被纳入研究。即使在具有相同FZD4变体的家族成员中,临床表型也是可变的。只有34%(N=12/35)的变异阳性个体被临床诊断为FEVR。出现症状的中位年龄为2.3岁,在0到25年之间。视力中位数为0.1logMAR（0.8Snellen十进制），介于光感知和-0.1logMAR（1.25Snellen十进制）之间。大多数（N=33/35，94％）被归类为非视力障碍。尽管有些人存在单侧视力丧失，根据WHO分类,他们不符合视力损害标准.两名研究患者（N=2/35，6％）有严重的视力障碍。研究患者眼睛中最常见的FEVR阶段（N=28/70眼，40%)是FEVR阶段1，即，无血管外周或异常血管化。大多数FZD4变异阳性研究患者的眼睛（N=31/50眼，62%)为近视。两个个体表现出持续的增生性原始玻璃体，从而扩大了FEVR的表型谱。鉴定了在复发的FZD4c.31A>G变体周围延伸约0.9Mb的共享单倍型。
结论：大多数研究患者未受到FEVR的影响或有轻微的临床表现。近视在FZD4变异阳性个体中似乎过于普遍。
方法：收集并分析了35例FZD4杂合致病变异个体的详细临床和遗传数据。
结果：32名具有FZD4c.31A>G变体的个体和3名具有FZD4c.40_49del的个体被纳入研究。即使在具有相同FZD4变体的家族成员中,临床表型也是可变的。只有34%(N=12/35)的变异阳性个体被临床诊断为FEVR。出现症状的中位年龄为2.3岁,在0到25年之间。视力中位数为0.1logMAR（0.8Snellen十进制），介于光感知和-0.1logMAR（1.25Snellen十进制）之间。大多数（N=33/35，94％）被归类为非视力障碍。尽管有些人存在单侧视力丧失，根据WHO分类,他们不符合视力损害标准.两名研究患者（N=2/35，6％）有严重的视力障碍。研究患者眼睛中最常见的FEVR阶段（N=28/70眼，40%)是FEVR阶段1，即，无血管外周或异常血管化。大多数FZD4变异阳性研究患者的眼睛（N=31/50眼，62%)为近视。两个个体表现出持续的增生性原始玻璃体，从而扩大了FEVR的表型谱。鉴定了在复发的FZD4c.31A>G变体周围延伸约0.9Mb的共享单倍型。
结论：大多数研究患者未受到FEVR的影响或有轻微的临床表现。近视在FZD4变异阳性个体中似乎过于普遍。
