Primary Dwarfism, Microcephaly, and Chorioretinopathy due to a PLK4 Mutation in Two Siblings

Abstract

<b><i>Introduction:</i></b> 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 <i>PLK4</i> gene<i>,</i> 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. <b><i>Case Presentation:</i></b> Here, we describe 2 siblings of different sex from Equatorial Guinea harboring a homozygous frameshift mutation in <i>PLK4</i> (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. <b><i>Discussion/Conclusion:</i></b> Biallelic variants in <i>PLK4</i> 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.