背景:小头症伴或不伴脉络膜视网膜病变,淋巴水肿,或智力低下是一种罕见的常染色体显性遗传疾病,由KIF11突变引起,破坏EG5蛋白功能,由于其在视网膜感光纤毛中的表达,影响视网膜和淋巴结构的发育和维持。MCLMR的主要眼部发现是脉络膜视网膜病变。额外的功能可以包括小眼症,闭角型青光眼,持续性增生性原发性玻璃体,白内障,假性结肠瘤,持续性玻璃样动脉,和近视或远视散光。脉络膜视网膜病变的外观为白色至粉红色,圆形,没有血管的非升高的萎缩性区域类似于艾卡迪综合征的腔隙。由于缺乏对病变的系统描述和显着的表型变异性,每个案件都需要一份详细的报告。
方法:一名在妊娠晚期发现小头畸形的儿童,由于视觉上无意义的白内障,开始在眼科随访。不久之后,她出现了眼球震颤和交叉固定的大角度交替内斜视。她的眼底最初显示出苍白的视盘和色素变化,此后发展视网膜腔隙和视网膜褶皱。她的鉴别诊断伴随着眼底的动态变化,其中包括先天性感染,Leber先天性黑蒙和艾卡迪综合征。在19个月大的时候,遗传检测确定了杂合突变(c.1159C>T,p.Arg387*)在KIF11基因中。患者在2岁时因持续性内斜视接受了双侧内侧直肌收缩手术,有显著的改进。屈光度显示双眼远视散光(0.25-2.50×180OD和0.75-2.00×170OS)。她仍然需要每天2小时的右眼修补。
结论:该病例报告通过展示独特的视网膜特征组合,扩展了MCLMR的表型谱,为Aicardy综合征的鉴别诊断提供了新的思路。我们的发现强调了与MCLMR相关的显着表型变异性,尤其是眼部受累。这强调了详细的临床评估和全面报告病例的重要性,以提高我们对疾病谱和基因型-表型相关性的理解。
BACKGROUND: Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation is a rare autosomal dominant disease caused by mutations in KIF11 which disrupt EG5 protein function, impacting the development and maintenance of retinal and lymphatic structures due to its expression in the retinal photoreceptor cilia. The primary ocular finding in MCLMR is chorioretinopathy. Additional features can include microphthalmia, angle-closure glaucoma, persistent hyperplastic primary vitreous, cataract, pseudo-coloboma, persistent hyaloid artery, and myopic or hypermetropic astigmatism. The appearance of the chorioretinal lesions as white to pinkish, round, non-elevated atrophic areas devoid of blood vessels resembles the lacunae in Aicardy syndrome. Due to the lack of systematic description of the lesions and significant phenotypical variability, there is an impending need for a detailed report of each case.
METHODS: A child with microcephaly detected in the third trimester of gestation began her following in the ophthalmology department due to a non-visually significant cataract. Shortly after, she developed nystagmus and large-angle alternating esotropia with cross-fixation. Her fundus initially showed a pallid optic disc and pigmentary changes, developing thereafter retinal lacunae and a retinal fold. Her differential diagnosis accompanied the dynamic changes in her fundus, which included congenital infections, Leber´s Congenital Amaurosis and Aicardy syndrome. At 19 months old, genetic testing identified a heterozygous mutation (c.1159 C > T, p.Arg387*) in the KIF11 gene. The patient underwent bilateral medial rectus muscle recession surgery at 2 years old for persistent esotropia, with significant improvement. Refraction revealed a hyperopic astigmatism in both eyes (+ 0.25 -2.50 × 180 OD and + 0.75 -2.00 × 170 OS). She continues to require right eye patching for 2 hours daily.
CONCLUSIONS: This case report expands the phenotypic spectrum of MCLMR by demonstrating a unique combination of retinal features which sheds new light on differential diagnosis from Aicardy syndrome. Our findings emphasize the significant phenotypic variability associated with MCLMR, particularly regarding ocular involvement. This underscores the importance of detailed clinical evaluation and comprehensive reporting of cases to improve our understanding of the disease spectrum and genotype-phenotype correlations.