A novel KIF11 mutation in a Turkish patient with microcephaly, lymphedema, and chorioretinal dysplasia from a consanguineous family

Abstract

Microcephaly–lymphedema–chorioretinal dysplasia (MLCRD) syndrome is a rare syndrome that was first described in 1992. Characteristic craniofacial features include severe microcephaly, upslanting palpebral fissures, prominent ears, a broad nose, and a long philtrum with a pointed chin. Recently, mutations in KIF11 have been demonstrated to cause dominantly inherited MLCRD syndrome. Herein, we present a patient with MLCRD syndrome whose parents were first cousins. The parents are unaffected, and thus a recessive mode of inheritance for the disorder was considered likely. However, the propositus carries a novel, de novo nonsense mutation in exon 2 of KIF11. The patient also had midline cleft tongue which has not previously been described in this syndrome. © 2012 Wiley Periodicals, Inc.

Ocular manifestations of microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) syndrome associated with mutations in KIF11

“…As in the present series, ERG data from one family with confirmed KIF11 mutation (Hazan et al. ) and another with dominant inheritance but without molecular data (Simonell et al. ) showed subnormal and delayed rod and cone ERGs.…”

“…In this series, the ERGs were of borderline timing in case 1 but all others showed some evidence of significant delay in at least one ERG parameter, suggesting generalized retinal dysfunction. There are few reports of retinal electrophysiology in association with MCLID in the literature (Manning et al 1990;Feingold & Bartoshesky 1992;Atchaneeyasakul et al 1998;Hazan et al 2012), and most previously published data were acquired prior to the identification of KIF11 as the causative gene, with the largest ERG series acknowledging the likelihood of heterogeneity (Atchaneeyasakul et al 1998). As in the present series, ERG data from one family with confirmed KIF11 mutation (Hazan et al 2012) and another with dominant inheritance but without molecular data (Simonell et al 2002) showed subnormal and delayed rod and cone ERGs.…”

“…; Hazan et al. ), and most previously published data were acquired prior to the identification of KIF11 as the causative gene, with the largest ERG series acknowledging the likelihood of heterogeneity (Atchaneeyasakul et al. ).…”

Congenital microcephaly and chorioretinopathy due to de novo heterozygous KIF11 mutations: Five novel mutations and review of the literature

“…Heterozygous mutations in KIF11 , a gene encoding a spindle motor protein (EG5) of the Kinesin family, have been identified in 43 individuals from 25 families [Hazan et al, ; Ostergaard et al, ; Jones et al, ]. The most consistent features of mutation‐positive individuals are congenital MIC, ranging from mild to severe, and chorioretinal abnormalities.…”

Lymphatic Vessel Network Structure and Physiology

“…Tbx1 mutations are associated with DiGeorge syndrome; however, lymphatic defects so far have been reported only once as abdominal lymphatic dysplasia in patients with DiGeorge syndrome (649, 1162). Although the developmental function of Kruppel Like Factor 11 ( KLF11 ) remains unclear, its mutations cause microcephaly-lymphedema-chorioretinal dysplasia (MLCRD) syndrome (427, 823). More recently, homozygous and compound heterozygous mutations in PIEZO1 (encodes a mechanically activated ion channel), resulting in an autosomal recessive form of generalized lymphatic dysplasia (GLD) with a high incidence of non-immune hydrops fetalis and childhood onset of facial and four limb lymphedema.…”