Objective: The purpose of this observation is to demonstrate that autosomal recessive early parkinsonism is clinically and genetically heterogeneous

Background: Early Onset Parkinson’s disease is rare, more so in presence of atypia. We provided observations of two patients, a boy and a girl from an inbred (consanguine) Algerian family with autosomal recessive inheritance presenting an early onset Parkinson’s with atypia.
Both patients are carriers of a homozygous mutation p.R258Q of the gene SYNJ1 which codes for a protein synaptojanine1.

Method: It is the case of two patients, witch developed a Parkinsonism at age 21 and 26 respectively. Their background shows records of generalized tonic-clonic seizures , and an intellectual declin. The neurological exam established, beside the classical signs of early onset Parkinson’s:  dysarthria, sever cognitive deficiency and hypersalivation. The brain MRI showed no anomalies , copper levels serum was normal. The evolution under low dose dopaminergic treatment leads to a partial improvement of the clinical signs, but occurrence early and severe side-effects .The genetic study in this family revealed that these patients are carriers of a homozygous mutation p.R258Q of the gene SYNJ1.

Results: Usually , the recessive forms linked to Parkin mutations Pink1 & DJ1 have a homogenous phenotype without atypia, sensitive to the dopa therapy and its derivative. The phenotype of both our patients resulting from the homozygous mutation p.R258Q of gene SYNJ1 presents atypia :a response to dopa therapy, early and disabling side effects. This suggests that early onset Parkinson’s disease is clinically and genetically heterogeneous, thus evokes the term of Spectra of Parkinson’s disease.

Conclusion: Parkinson’s disease cases linked to a mutation of the gene SYNJ1 mentioned in literature are very rare. Our observations contribute to the extension of the clinical and genetic spectra of the disease. The mutation of gene SYNJ1 confirms the heterogeneity of early onset Parkinsonism ad opens research perspectives of the haplotypes of a common ancestor in a far-reaching (wide-ranging) study.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-a-new-homozygous-mutation-p-r258q-in-the-gene-synj1-of-an-algerian-consanguine-inbred-family-suffering-from-early-onset-atypical-parkinsonism/