This website provides information on patients with mutations in the ARFGEF1 gene, including clinical data, molecular data, management and research options.

The syndrome caused by mutations in the ARFGEF1 gene is mainly a neurodevelopmental disorder, characterized by a variable association of developmental delay, mild to severe intellectual disability, behavioural problems, and epilepsy ranging from focal motor epilepsy to Lennox-Gastaut like syndromes.

Clinical assessment may also reveal mild morphological features that typically include large and low-set ears, wide mouth, high forehead, bulbous nasal tip, and thin long facies.

Brain MRI may also be of interest in ARFGEF1 patients by revealing signs evocative of myelination delay (relative brain atrophy, enlarged ventricles, posterior and deep white matter hyperintensities) but also low-set cerebellar tonsils and most strikingly periventricular heterotopia.

Not all individuals with a mutation in the ARFGEF1 gene have all these features and some patients may have mild forms with isolated and mild developmental delay, sometimes only affecting speech.

However, ARFGEF1 patients do not seem to have symptoms beyond the neurological sphere, for instance no patient has been reported to carry significant cardiac or pulmonary malformation.

Interestingly, ARFGEF1 pathogenic variants may be inherited from a mildly affected or even clinically asymptomatic father. This feature has never been observed from a mother, raising the question that women with ARFGEF1 pathogenic variants may have reduced fertility.

This website was created to share and collect information about clinic, management and research projects to gather more knowledge and provide better treatment of patients with mutations in the ARFGEF1 gene.

Quentin Thomas, MD, PhD, Reference Center for Rare Neurogenetic disorders, Dijon Burgundy Hospital, University of Burgundy Europe, Dijon, France, Quentin.thomas@chu-dijon.fr

Antonio Vitobello, PhD, Team GAD, University of Burgundy Europe, Dijon, France, Antonio.vitobello@ube.fr