Leukodystrophies and other hereditary leukoencephalopathies comprehensive panel [142 genes]

Leukodystrophies are a heterogeneous group of inherited disorders that affect the white matter of the central nervous system (CNS), regardless of the involved structural component, affected molecular processes, disease progression, or whether the peripheral nervous system is also affected. Numerous inherited conditions also affect white matter secondarily; these are known as genetic or inherited leukoencephalopathies. Thus, while primary leukodystrophies mainly affect glial cells, inherited leukoencephalopathies are disorders with primary neuronal, vascular, or systemic involvement in which changes in white matter are considered secondary. Therefore, although all leukodystrophies can be considered inherited leukoencephalopathies, not all inherited leukoencephalopathies are leukodystrophies.

These two groups of diseases include pathologies with onset from the neonatal period to adulthood, and, although each disease can have different characteristics, all of them show white matter abnormalities on magnetic resonance imaging (MRI) or CNS pathologies, and movement disorders usually dominate the clinical picture, particularly in younger individuals. Due to their complex diagnosis, the true prevalence and incidence of leukodystrophies as a group is difficult to establish, and combined incidence is estimated to be between 1/50 000 and 1/7,663 live-born infants. Generally, early recognition of a leukodystrophy can be complicated, since they are often insidious and clinically heterogeneous, and therefore usually not considered until abnormalities are detected on MRI. Even then, due to the limited knowledge on their etiology, they can go undiagnosed or be incorrectly diagnosed. While advances in pattern recognition in neuroimaging have improved diagnostic yield, current treatments are limited, and a definite diagnosis is essential for the correct management of symptoms, prognosis, and genetic counseling.