Expansion of Phenotyping and Genotypic Spectra of KIF7-Related Intellectual Disability: Case Report and Review of Literature.

Neurodevelopmental disorders (NDDs), which typically emerge in childhood, affect nervous system development. Recent studies have linked KIF7 mutations, which disrupt the Hedgehog signaling pathway essential for embryonic development, to certain features of NDDs. Here, we report two male siblings with intellectual disability, short stature, macrocephaly, epilepsy, Dandy-Walker malformation, dysmorphic facial features, cryptorchidism, and skeletal anomalies. Both siblings exhibited absence of fifth distal and middle phalanges bilaterally, which has never been previously reported. Whole-genome sequencing of both siblings and their parents demonstrated that the siblings were homozygous for a novel frameshift mutation, c.2975_2988del (p.Leu992ArgfsTer51) in KIF7, while their parents were heterozygous for the variant. These findings expand the phenotypic and mutational spectra of KIF7-associated intellectual disability. Additionally, we analyzed all previously reported cases of KIF7 mutations to investigate genotype-phenotype correlations, but no specific mutation type or functional domain was definitively associated with a particular phenotype.