Phenotypic and genotypic heterogeneity in a series of cases associated with dopa-responsive dystonia

Dopa-responsive dystonia (DRD) includes a group of neurological disorders that manifest with lower limb dystonia and an excellent response to levodopa. Parkinsonism is commonly associated with DRD, and many cases of GCH1 gene mutations without dystonia but with evidence of nigrostriatal pathway degeneration, indistinguishable to idiopathic Parkinson's disease (PD), have been recently described. This phenotypic variability has been observed even among members of the same family.

Clinical and genetic description of 14 patients from 4 different families with DRD associated mutations.

The results showed GCH1 mutations in three of the four families, while one family had a mutation in the SPR gene. Within patients with GCH1 mutations, two showed DRD symptoms, five had PD phenotype, and four were asymptomatic. The only patient with SPR mutation clinically displayed symptoms of dystonia and parkinsonism. DaTscan® revealed degeneration of the nigroestriatal pathway in two PD patients. Furthermore, phenotypic variability of the same mutation was observed in two families.

DRD associated mutations have a heterogeneous clinical expression GCH1 gene mutations can be manifested with PD phenotype along with the degeneration of the nigroestiatal pathway. Therefore, GCH1 gene testing might be useful in cases of PD suggestive of genetic origin or with family history of dystonia.