Families

The TFE3-associated neurodevelopmental syndrome is caused by mutations or changes 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.

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. Some male patients have been found to be mosaic for the TFE3gene change. This means that they have two different cell lines in blood, one with a normal gene copy and the other cell line with the TFE3gene change or mutation.

All the individuals (adults and children) with TFE3-associated neurodevelopmental disorder have delayed psychomotor development, usually noticeable from the first months of life. They latter develop moderate to severe intellectual disability. All share distinctive and coarse facial features.

Most of them have other neurological anomalies, such as epilepsy, hypotonia (low muscle tone) or autism. Pigmentation anomalies (darker or whiter lines on the skin, like stripes on the back or limbs), obesity and growth retardation are also frequent.

Common features are sleep disturbance, regression in the development of a child, flat feet, hyperlordosis (spinal curve), hearing and vision issues, recurrent infections.

Rarer, affected individuals can have skeletal problems (hip dislocation, knee anomalies), neonatal hepatomegaly (enlargement of the liver), lung disease, umbilical hernia, neonatal hypoglycaemia (low sugar in blood).