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 #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 sixteen families worldwide. This is a review of the condition based on the clinical features of thirty seven individuals from twenty two 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 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.