Autosomal recessive missense Rotatin (RTTN) mutations are responsible for syndromic forms of malformation of cortical development, ranging from isolated polymicrogyria to microcephaly associated with primordial dwarfism and other major malformations.
RTTN mutations have been reported in seven families and are associated with two phenotypes: polymicrogyria associated with seizures and primary microcephaly associated with primordial dwarfism.
Homozygous mutations in RTTN gene have been described in bilateral diffuse isolated polymicrogyria and, more recently, in microcephalic primordial dwarfism (PD).
Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration.