Abstract：
Raine syndrome (MIM 259775) is a rare autosomal recessive disorder, first described by Raine et al. in 1989, with an estimated prevalence of <1/1,000,000. This is due to pathogenic variants in FAM20C characterized by osteosclerosis, typical craniofacial features, and brain calcifications. Here, we report a novel variant in FAM20C, describe a uniquely severe craniofacial and CNS phenotype of Raine syndrome, and correlate it with prenatal findings. Fetal phenotyping was based on ultrasound and MRI. Solo exome sequencing was performed from DNA extracted from postmortem skin biopsy. Targeted parental variant testing was subsequently performed. A homozygous missense variant NM_020223.4 (c.1445 G > A (p.Gly482Glu)) was identified in FAM20C associated with Raine syndrome. The infant had the characteristic dysmorphic features seen in Raine syndrome. He had particularly significant CNS manifestations consisting of multisuture craniosynostosis with protrusion of the brain parenchyma through fontanelles and cranial lacunae. Histological sections of the brain showed marked periventricular gliosis with regions of infarction, hemorrhage, and cavitation with global periventricular leukomalacia. Numerous dystrophic calcifications were diffusely present. Here, we demonstrate the identification of a novel variant in FAM20C in an infant with the characteristic features seen in Raine syndrome. The patient expands the characteristic phenotype of Raine syndrome to include a uniquely severe CNS phenotype, first identified on prenatal imaging.
摘要：
雷恩综合征（MIM259775）是一种罕见的常染色体隐性遗传病，首先由Raine等人描述。1989年，估计患病率<1/1,000,000。这是由于FAM20C中的致病变体以骨硬化为特征，典型的颅面特征,脑钙化.这里,我们报道了FAM20C中的一个新变体，描述一个独特的严重的颅面和中枢神经系统表型的雷恩综合征，并将其与产前发现相关联。胎儿表型基于超声和MRI。从死后皮肤活检提取的DNA进行Solo外显子组测序。随后进行靶向亲本变体测试。纯合错义变体NM_020223.4（c.1445G>A（p。Gly482Glu））在FAM20C中与雷因综合征相关。婴儿具有雷恩综合征中的特征性异形特征。他的中枢神经系统表现特别明显，包括多缝线颅骨融合，脑实质通过font门和颅腔隙突出。大脑的组织学切片显示明显的脑室周围胶质增生，并伴有梗死区域，出血,和空化伴整体脑室周围白质软化。弥漫性存在许多营养不良性钙化。这里,我们证明了FAM20C在具有雷恩综合征特征性特征的婴儿中的新变异体的鉴定。患者扩大了雷恩综合征的特征性表型，包括一个独特的严重CNS表型，首次在产前成像中发现。
