Cerebellofaciodental syndrome (MIM #616202) is an autosomal recessive condition characterized by intellectual disability, microcephaly, cerebellar hypoplasia, dysmorphic features, and short stature. To date, eight patients carrying biallelic BRF1 variants have been reported. Here, we describe two siblings with congenital microcephaly and corpus callosum hypoplasia, pre and postnatal growth retardation, congenital heart defect and severe global developmental delay. We also detected additional findings not previously reported in this syndrome, including bilateral sensorineural hearing impairment and inner ear malformation. Whole exome sequencing identified a novel homozygous missense variant (c.654G>C, p.[Trp218Cys]) in BRF1, predicted to affect the protein structure. Expression assessment showed extremely low BRF1 protein expression caused by the identified variant, supporting its causal involvement. The description of new patients with cerebellofaciodental syndrome is essential to better delineate the phenotypic and genotypic spectrum of the disease.

中文翻译：

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扩大小脑-面部-牙齿综合症的表型：BRF1中具有新变异的两个兄弟姐妹。

小脑口齿综合症（MIM＃616202）是常染色体隐性遗传病，特征是智力残疾，小头畸形，小脑发育不全，畸形和身材矮小。迄今为止，已经报道了八名携带双等位基因BRF1变体的患者。在这里，我们描述了先天性小头畸形和体发育不全的两个兄弟姐妹，产前和产后发育迟缓，先天性心脏缺陷和严重的整体发育延迟。我们还检测到了以前未在该综合征中报告的其他发现，包括双侧感觉神经性听力障碍和内耳畸形。整个外显子测序鉴定了新的纯合错义变异体（c.654G> C，第[Trp218Cys]）在BRF1，预计会影响蛋白质结构。表达评估表明，由鉴定出的变异引起的BRF1蛋白表达极低，支持其因果关系。对新的小脑口齿综合征患者的描述对于更好地描述该疾病的表型和基因型谱至关重要。