Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation associated with KIF11 pathogenic variant: case report and genotype-phenotype correlation analysis.

backgroundMicrocephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) is a rare autosomal dominant disease caused by variants in the KIF11 gene. Additionally, recent advances in genetic testing have led to the increasing identification of KIF11 gene variants in FEVR patients. Harboring similar point variants in the KIF11 gene, patients exhibit striking variability in clinical manifestations. However, comprehensive clinical characterization of MCLMR patients with KIF11 variants are only mentioned by a few case reports and the genotypic and phenotypic variability in KIF11-associated disease was not thoroughly investigated. Therefore, one case is discussed alongside a systematic review of published MCLMR cases to clarify genotype-phenotype correlations. CASE PRESENTATION: An 8-year-old boy was referred to our clinic due to poor vision. Clinical evaluation revealed microcephaly, characteristic chorioretinopathy and mild developmental delay, in the absence of primary lymphedema. Additional findings included special facial features, bilateral simian crease and metabolic abnormalities featuring elevated urine glucose and ketone bodies despite normoglycemia. Brain magnetic resonance imaging (MRI) demonstrated microcephaly with simplified gyration, delayed myelination, and cortical thickening. Whole exome sequencing (WES) identified a previously reported synonymous variant in KIF11 (c.2922G > A, p.Pro974=), which was confirmed and co-segregated by Sanger sequencing.

conclusionsA Chinese boy was diagnosed with MCLMR following the identification of a pathogenic KIF11 gene point variant, as classified according to ACMG guidelines. Combined with previously reported literature, a total of 55 pathogenic KIF11 variants have been identified, distributed throughout the entire gene. A recurrent mutational hotspot (c.1159 C > T, p.Arg238*) was observed. Additionally, frameshift and splicing variants collectively account for over 50% of cases. Notably, missense variants are associated with more severe phenotypic manifestations, suggesting a genotype-phenotype correlation. This case, supported by comprehensive clinical data, contributes to a more complete elucidation of the phenotypic spectrum of KIF11-related disorders.