Introduction: Primary autosomal recessive microcephalies (MCPHs) are characterized by primary dwarfism with MCPH and may present delayed psychomotor development and visual impairment. Biallelic loss of function variants in the PLK4 gene, which encodes the polo-like kinase 4 protein involved in centriole biogenesis, has been recently identified in several patients with MCPH and various ethnic backgrounds. Case Presentation: Here, we describe 2 siblings of different sex from Equatorial Guinea harboring a homozygous frameshift mutation in PLK4 (c.1299_1303del, p.Phe433Leufs*6). A Seckel syndrome spectrum phenotype was present in both siblings, with short stature, severe MCPH, reduced brain volume, and distinctive facial features. They also presented severe intellectual disability, lissencephaly/pachygyria, subependymal heterotopia, and ophthalmological impairment. One of them suffered from deafness, and scoliosis was observed in the other. Discussion/Conclusion: Biallelic variants in PLK4 lead to a syndrome where severe short stature, MCPH, and cognitive impairment are constant features. However, ocular, skeletal, and other neurological manifestations can vary upon the same genetic basis.
Horm Res Paediatr

中文翻译：

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两个兄弟姐妹的 PLK4 突变导致的原发性侏儒症、小头畸形和脉络膜视网膜病变

简介：原发性常染色体隐性遗传小头畸形 (MCPHs) 的特征是伴有 MCPH 的原发性侏儒症，可能会出现精神运动发育迟缓和视力障碍。PLK4基因中的双等位基因功能缺失变体编码参与中心粒生物发生的 polo 样激酶 4 蛋白，最近已在几名 MCPH 和不同种族背景的患者中发现。案例介绍：在这里，我们描述了来自赤道几内亚的 2 个不同性别的兄弟姐妹，它们在PLK4中具有纯合移码突变（c.1299_1303del，p.Phe433Leufs*6）。两个兄弟姐妹都存在 Seckel 综合征谱表型，身材矮小、严重 MCPH、脑容量减少和独特的面部特征。他们还表现出严重的智力障碍、无脑回畸形/脑回症、室管膜下异位和眼科障碍。其中一人耳聋，另一人出现脊柱侧弯。讨论/结论： PLK4中的双等位基因变异导致严重身材矮小、MCPH 和认知障碍是持续特征的综合征。然而，眼部、骨骼和其他神经系统表现在相同的遗传基础上可能会有所不同。
儿科荷尔蒙