The TFE3-associated neurodevelopmental syndrome is caused by mutations in the TFE3gene and is characterized by the triad of abnormal linear skin pigmentation, intellectual disability, and lysosomal storage-like features, mainly coarse facial features. Epilepsy, hypotonia, obesity, growth retardation, autistic behaviour, visual and hearing impairment are frequent associated features.
This X-linked lysosomal genetic condition is rare and has only been reported in around 20 individuals. Patients are usually female, but at least 5 males have been reported with the characteristic triad, and 2 of them have been mosaic in blood. All patients described to date have a de novovariant in TFE3gene. All are missense variants and localized in exons 3 and 4 of the gene, except for one splice site variant localized in intron 4. Four are recurrent variants.
Genetic counselling:since the pathogenic variant occurred de novo in all patients, the recurrence risk in siblings of probands is low, limited to the theoretical possibility of germline mosaicism.
Management:treatment is symptomatic and multidisciplinary.
TFE3