Joern Bullerdiek; Andreas Dotzauer; Ingrid Bauer

“ MLCRD (microcephaly, primary lymphedema, and chorioretinal dysplasia) syndrome (MIM 152950, OMIM) and CDMMR (chorioretinal dysplasia, microcephaly, and mental retardation) syndrome (MIM 156590) [9] , [10] . In MLCRD the main ocular abnormalities are bilateral chorioretinopathy, but optical nerve abnormalities do occur as well [11] . Interestingly, in both syndromes heterozygous mutations of the KIF11 (Kinesin Family Member 11) gene encoding EG5, a spindle motor protein of the kinesin-5 family were found [10] . ”

“ In addition to microcephaly associated with other syndromic features, most of the genetic causes of ‘primary’ developmental microcephaly are known to be associated with dysfunction of centrosomal proteins controlling the mitotic spindle assuring normal cell proliferation during mitosis [8] . Akin to isolated microcephaly, the combination of microcephaly with chorioretinal abnormalities also seems to be related to mutations of genes involved in proper spindle function:
As for autosomal-dominant inheritance, a phenotypic overlap can be noted between two syndromes i.e. ”

“ After termination of the pregnancy, the presence of ZIKV was demonstrated in the fetal brain and the whole genome of ZIKV was recovered by using next generation sequencing [4] , (GenBank deposition number KU527068) . A causal relationship has been presumed [5] , [6] and this association was the major reason that prompted the WHO to declare a Public Health Emergency of International Concern (PHEIC) . ”

“ Vice versa, as a straightforward approach one might also consider testing newborns with microcephaly that may be associated with maternal ZIKV infection for germline mutations of the genes mentioned but the rarity of these syndromes makes such an explanation unlikely. ”