Clinical Characteristics

The two major neuroradiological findings observed in individuals with a heterozygous pathogenic end-truncating variant are:
•    An episodic memory dysfunction of the hippocampal type starting during the sixth decade
•    confluent, extensive homogeneous, bilateral, and symmetrical white matter hyperintensities. The periventricular, deep, and superficial hemispheric white matter are involved simultaneously, without lobar predominance, leading to a diffuse leukoencephalopathy.

The prevalence and penetrance of these mutations are currently unknown.

Several differential diagnoses can be raised due to this unusual clinical and MRI association, including i) Alzheimer- like disease because of the similarity of cognitive impairments ii) cerebral small vessel diseases because of the diffuse leukoencephalopathy iii) leukodystrophy or neurometabolic inherited conditions because of the diffuse leukoencephalopathy detected on MRI.