Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR): review of phenotype associated with KIF11 mutations

Abstract

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing.

Optical coherence tomography of macular atrophy associated with microcephaly and presumed intrauterine Zika virus infection

“…The definitive laboratory method to diagnose ZIKV infection is real time-PCR, which has limited utility after the acute stage (2) . Chorioretinal disorders are associated with microcephaly of varying etiologies, including infections (STORCH complex) (3) and ge netic conditions (4) . Intrauterine infection with the West Nile Virus, another flavivirus, was also reported to cause chorioretinal scarring (3) .…”

Novel compound heterozygous variants in PLK4 identified in a patient with autosomal recessive microcephaly and chorioretinopathy

“…8 A persistent hyperplastic primary vitreous is included in the chorioretinopathy caused by the mutations in KIF11. 9 The clinical features of our current patient accorded with those of MCCRP.…”

A Novel Mutation of KIF11 in a Child with 22q11.2 Deletion Syndrome Associated with MCLMR

“…EG5 possibly also has a role in the cilia [Birtel et al, 2017]. Jones et al [2014] assessed 37 individuals with KIF11 mutations and found microcephaly, ocular abnormality, lymphedema, epilepsy, and cardiac anomaly as major clinical features. The OFCs of the patients ranged from -9.5 to -1.1 SDs.…”

“…KIF11 encodes a homotetrameric protein, EG5, which drives microtubule sliding and contributes to the assembly of the mitotic spindle [Valentine et al, 2006;Jones et al, 2014]. EG5 also has non-mitotic functions such as involvement in endothelial cell lineage proliferation, secretory protein trans portation, and protein translation [Bar- , 2011;Exertier et al, 2013;Wakana et al, 2013].…”