Abstract
Rett syndrome is a well-defined neurodevelopmental disorder comprising characteristic clinical features of gait abnormalities, loss of purposeful hand movements, stereotypies, and autistic features. Mutations in the FOXG1 gene have been associated with a congenital variant of Rett syndrome. This is a report on the outcome of routine genetic testing to identify FOXG1 mutations in a patient population presenting with features of the FOXG1 syndrome, an entity thought to be distinct, but similar, to the congenital variant of Rett syndrome. We performed PCR and sequencing analysis of FOXG1 in MECP2-negative patients (n = 12) with phenotypic features of FOXG1 syndrome. FOXG1 MLPA analysis was also carried out. No mutations in FOXG1 were identified using this approach. We were unable to identify patients with features of the FOXG1 syndrome as having aberrant FOXG1 gene loci. Clinical notes are inherently subjective and may lack sufficient detail to reliably identify those with a syndromal spectrum. The results call into question the objectivity of outlining a complex syndrome according to clinical manifestations and highlight the need for a greater involvement of molecular diagnostic techniques in the diagnosis of Rett-like disorders.