Novel KIF11 Variants with New Clinical Features: Expanding the Clinical Phenotype.

Monoallelic KIF11 variants are associated with Microcephaly with or without Chorioretinopathy, Lymph-edema, or Impaired Intellectual Development (MCLMR) (OMIM:152950). This study presents seven patients from two distinct families, exhibiting extreme clinical heterogeneity, along with novel clinical findings and genetic variants. Patient 1 presented with learning difficulties, epilepsy, behavioral abnormalities, and various ocular anomalies, in addition to microcephaly and facial dysmorphism. Patient 2 was prenatally diagnosed with dorsal pedal edema, which was confirmed postnatally, alongside facial dysmorphic features and the need for craniosynostosis surgery at four months. Peripheral blood samples were obtained for DNA isolation, and Whole Exome Sequencing (WES) was performed for molecular analysis. Whole-exome sequencing (WES) revealed a de novo heterozygous frameshift variant in the KIF11 gene (NM_004523.4: c.2224_2225del; p. Asn742TyrfsTer6) in patient 1, and a novel heterozygous frameshift variant (NM_004523.4: c.2946dup; p. Leu983SerfsTer6) in the same gene in patient 2. Segregation analysis demonstrated that Patient 2's variant was inherited from the mother and was also present in the maternal grandmother, sister, and two aunts. Our findings highlight the broad clinical heterogeneity of MCLMR syndrome, as Patient 1 exhibited keratoconus, optic nerve hypoplasia, behavioral problems, and seizures, which are rarely reported. Additionally, Patient 2 represents the first documented patient of prenatal lymphedema detection in MCLMR syndrome. Furthermore, craniosynostosis, identified in two patients (P2 and P5), has not been previously described, suggesting a potential novel phenotypic feature. These findings expand the genotypic and phenotypic spectrum of KIF11-related disease.