Neuropediatrics 2015; 46 - PS01-15
DOI: 10.1055/s-0035-1550682

Postnatal Microcephaly, Dyskinesia, and Agenesis of the Corpus Callosum as Indication of FOXG1-Related Disorders: A Case Report

S. Karch 1, N. Dikow 2, A. Seitz 3, J. Pietz 1
  • 1Neuropädiatrie, Zentrum für Kinder- und Jugendmedizin, Heidelberg, Germany
  • 2Institut für Humangenetik, Heidelberg, Germany
  • 3Abteilung Neuroradiologie, Neurologische Klinik, Heidelberg, Germany

Introduction: Point mutations or copy number variations in the FOXG1 gene result in developmental encephalopathy, also called congenital variant of Rett Syndrome (MIM 613454). Clinical features include severe mental retardation, absent speech, autistic behavior, and epilepsy. Furthermore, deletions of 14q12 including FOXG1 or intragenic mutations are associated with severe postnatal microcephaly, dyskinesia, and malformations of the corpus callosum. Patients carrying duplications of 14q12 show in contrast normal head size and corpus callosum morphology.

Case Report: The boy was born at term to healthy parents after normal pregnancy with 3,530 g birth weight (P41), 52 cm (P39) height, and 33.5 cm (P5) head circumference. During the first 3 months, irritability and a poor sleep pattern appeared; later poor eye contact and decelerating head circumference were noticed. On examination at 12 months of age, hypotonia and dystonic hand movements were observed. Psychomotor development was significantly retarded. At the age of 2.5 years, he was able to grasp, to turn, and to crawl. He could speak four to five single words. He never had epileptic seizures. Multiple EEGs revealed no epileptic activity. His brain MRI displayed an agenesis of the corpus callosum and a delayed myelination. Routine chromosome analysis and array CGH as well as metabolic diagnostic yielded normal results. By sequencing FOXG1, a pathogenic mutation (c.256delC, p.Q86Rfs*106) in the heterozygous state was detected.

Discussion: Even in the absence of epilepsy, a FOXG1-related disorder should be considered for children showing a severe postnatal microcephaly, severe mental retardation, dyskinesia, and malformation of the corpus callosum. In these cases, a detailed genetic analysis including sequencing of FOXG1 is required.

Keywords: FOXG1, postnatal microcephaly, mental retardation, agenesis of the corpus callosum.