Leukodystrophies with spinal cord involvement on MRI panel [5 genes]
One of the hallmark characteristics of a particular group of leukodystrophies is spinal cord involvement. Among these diseases, it is worth highlighting adult-onset autosomal dominant leukodystrophy (ADLD), caused by heterozygous duplications in the LMNB1 gene and clinically characterized by autonomic dysfunction, pyramidal signs, and cerebellar ataxia with onset between the 4th and 5th decades of life. In this case, abnormalities on MRI (hyperintensity on T2 or FLAIR imaging) are more prominent in frontoparietal white matter, cerebellar peduncles, corticospinal tract, and the corpus callosum.
Other disorders with spinal cord involvement are adrenoleukodystrophy, Alexander disease, hypomyelination with brainstem and spinal cord involvement and leg spasticity, and leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation, caused by alterations in ABCD1, GFAP, DARS, and DARS2, respectively.
Priority Genes : Genes where there is sufficient evidence (clinical and functional) to consider them associated with the disease; they are included in the clinical practice guidelines.
Secondary Genes: Genes related to the disease, but with a lower level of evidence or that constitute sporadic cases.
* Candidate Genes: Not enough evidence in humans, but potentially associated with the disease.
- GFAP: Alexander disease
- DARS: Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL)
- LMNB1: Adult-onset autosomal dominant leukodystrophy (ADLD)
- DARS2: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL)