目的表征中央凹发育不全（FH）的基因型和表型谱。
多中心，观察性研究。
总共907名确诊为白化病分子诊断的患者，PAX6,SLC38A8,FRMD7,AHR,或来自9个国家的12个中心的全色盲（n=523）或从以前报道的文献中公开提供的数据集（n=384）中提取。
在2011年1月至2021年3月期间，从12个中心或文献中确定了具有确认分子诊断和中央凹OCT扫描可用性的个体。通过序列分析证实了基因诊断。FH的分级来源于OCT扫描。
FH等级,是否存在感光器特化(PRS+与PRS-),分子诊断,和视敏度（VA）。
我们队列中典型FH最常见的遗传病因是白化病（67.5％），其次是PAX6（21.8%），SLC38A8（6.8%），和FRMD7（3.5％）变体。AHR变异罕见（0.4%）。在67.4%的色盲病例中发现非典型FH。色盲中非典型FH的VA明显低于典型FH（P<0.0001）。根据分子诊断，FH等级的光谱存在显着差异（卡方=60.4，P<0.0001）。SLC38A8例均为PRS-(P=0.003),所有FRMD7病例均为PRS+(P<0.0001)。白化病亚型分析显示，与眼白化病（OA）和Hermansky-Pudlak综合征（HPS）相比，眼皮肤白化病（OCA）的FH等级（卡方=31.4，P<0.0001）和VA（P=0.0003）存在显着差异。与OCA相比，眼白化病和HPS的FH等级更高，VA更差。与FH相关的其他诊断相比，FRMD7变体之间的VA存在显着差异（P<0.0001）。
我们表征了FH的表型和基因型谱。非典型FH的预后比所有其他形式的FH更差。在典型的FH中，我们的数据表明，在SLC38A8，OA，HPS,和AHR变体以及后来的FRMD7变体。OCA和PAX6变体的中央凹发育停滞的定义时间段似乎显示出更多的变异性。我们的发现提供了对与FH相关的疾病的机械见解，并具有重要的预后和诊断价值。
To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH).
Multicenter, observational study.
A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384).
Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans.
Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA).
The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH.
We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.
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