title: Congenital microcephaly and chorioretinopathy due to de novo heterozygous KIF11 mutations: five novel mutations and review of the literature.
abstract: The microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome is a distinct microcephaly syndrome. The hallmark features, microcephaly, chorioretinopathy, and lymphedema are frequently recognized at birth. Another clinical entity, the chorioretinal dysplasia, microcephaly and mental retardation syndrome (CDMMR) is a highly overlapping syndrome characterized by more variable lymphedema. Recently, heterozygous mutations in KIF11, a gene encoding a critical spindle motor protein of the Kinesin family, have been reported in individuals with MLCRD, and in individuals with CDMMR. This finding is suggestive of a single clinically variable spectrum. Here, we report on de novo novel mutations of KIF11 in five individuals with severe microcephaly, marked simplification of the gyral pattern on neuroimaging, bilateral chorioretinopathy, and developmental delay. Three patients had congenital lymphedema, and one had congenital bilateral sensorineural hearing loss. This report, therefore, further expands the clinical and molecular spectrum of KIF11-associated microcephaly.
authors.affiliation: Division of Genetic Medicine, Department of Pediatrics, University of Washington and Center for Integrative Brain Research Seattle Children's Research Institute, Seattle, Washington; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
authors.forename: Ghayda M
authors.initials: GM
authors.lastname: Mirzaa
authors.forename: Laura
authors.initials: L
authors.lastname: Enyedi
authors.forename: Gretchen
authors.initials: G
authors.lastname: Parsons
authors.forename: Sarah
authors.initials: S
authors.lastname: Collins
authors.forename: Livija
authors.initials: L
authors.lastname: Medne
authors.forename: Carissa
authors.initials: C
authors.lastname: Adams
authors.forename: Thomas
authors.initials: T
authors.lastname: Ward
authors.forename: Bradley
authors.initials: B
authors.lastname: Davitt
authors.forename: Alma
authors.initials: A
authors.lastname: Bicknese
authors.forename: Elaine
authors.initials: E
authors.lastname: Zackai
authors.forename: Helga
authors.initials: H
authors.lastname: Toriello
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: Susan
authors.initials: S
authors.lastname: Christian
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005091:Exons; D019066:Facies; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D016547:Kinesins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D015792:Retinal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome
chemical_list: C470243:KIF11 protein, human; D016547:Kinesins
keywords: KIF11; chorioretinopathy; lymphedema; microcephaly