Clinical and genetic study of familial Parkinson’s disease in Tunisia

Abstract

Objective: To determine inheritance patterns and clinical characteristics of familial PD (F-PD) in Tunisia.

Methods: Twenty-one index patients were selected on the basis of typical PD and a family history of PD. The 21 families of the index patients were visited at home, and clinical assessment of all available relatives, a total of 133 individuals, was made. Extensive pedigree data detected 67 additional cases. We ascertained medical history, age, age at onset, first sign at onset, course of the disease, dosage and duration of levodopa (LD) treatment, and associated diseases. One patient from each family was hospitalized to confirm response to LD by evaluation of untreated and treated Unified Parkinson’s Disease Rating Scale scores. The sex ratio, transmission pattern, ancestral secondary cases, and segregation ratio (SR) were determined by pedigree analysis.

Results: Eighty-eight patients were analyzed (44 men and 44 women; mean age at onset, 39.8 ± 14.4 years). Pedigree analysis showed 10 single-generation (SG) families (i.e., all affected members belonging to 1 generation) and 11 multigenerational (MG) families (i.e., affected members spanning >1 generation). Parental consanguinity was more frequent in SG families than in MG families. The SR in SG families was 0.23 ± 0.05, compatible with autosomal recessive (AR) inheritance. Analysis of MG pedigrees showed autosomal dominant (AD) inheritance with reduced penetrance in 9 of 10 families. Age at onset was younger than in sporadic PD. Intrafamilial variability of age at onset, symptom of onset, and clinical course was observed. There was no difference in clinical characteristics between SG and MG families apart from dystonic foot at onset, which was more frequent in SG families.

Conclusions: First, F-PD is clinically similar to sporadic PD apart from younger age at onset. Second, there is intrafamilial and interfamilial variability of all clinical features. Third, F-PD in Tunisia is genetically heterogenous with at least two inheritance patterns: AD and AR.