ALS and CHARGE syndrome: a clinical and genetic study

Amyotrophic Lateral Sclerosis and CHARGE syndrome are complex neurological disorders, which never occurred together in the same family and, to date, no putative correlation between them has been described on PubMed Central. Due to our aim was to evaluate the presence of different genetic variants involved in these pathologies, we reported a clinical and genetic description of two sisters affected by these two different disorders. In the CHARGE patient, molecular analysis of the CHD7 gene revealed the c.8016G >A de novo variant in exon 37. The ALS patient had been screened negative for mutations in SOD1, TARDBP, FUS/TLS, C9orf72 and KIF5A genes. Anyway, targeted next generation sequencing analysis identified known and unknown genetic variations in 39 ALS-related genes: a total of 380 variants were reported, of which 194 in the ALS patient and 186 in the CHARGE patient. To date, although the results suggest that the occurrence of the two syndromes in the same family is co-incidental rather than based on a causative genetic variant, we could hypothesize that other factors might act as modulators in the pathogenesis of these different phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13760-018-1029-2) contains supplementary material, which is available to authorized users.