National & Kapodistrian University of Athens, Greece
Dr Serafeim Katsavos is a military neurologist and a PhD student of the National & Kapodistrian University of Athens (NKUA), examining the characteristics of familial Multiple Sclerosis in Greece. He gained expertise in Neuroimmunology as clinical fellow of the Dept of Clinical Neurosciences, in Addenbrooke’s CUH, and authored several scientific publications on Multiple Sclerosis pathophysiology and treatment.
Approximately 10% of Multiple Sclerosis (MS) patients have at least one relative who is also affected (familial MS/ fMS). Nevertheless, only scarce systematic attempts of further describing fMS have been done so far. In this study we examined the clinical, imaging and genetic profile traits of 123 fMS patients, compared to 275 sporadic cases (sMS). Methodology: Patients recruited underwent medical interview (demographic, clinical and family history data) and disability assessment, while their MRI-scans were analyzed for lesion distribution. HLA-DRB1 genotyping was performed for 53 non-related fMS and 52 sMS patients. Comparisons with HLA-DRB1 allelic frequencies, of a previously published sample of healthy controls (HC), were also performed. Findings: 47% of fMS cases had a 1st degree relative affected, while the rest had a 2nd or 3rd degree relative. Only the former subgroup had significantly younger age at disease onset (AAO) compared to sMS cases (mean AAO 28.3 vs 31.2 years, p=0.042). AAO anticipation was noted in younger generation fMS patients (mean AAO 23.3 years vs 40.3 years in older generation, p=0.001). With regard to MRI findings, brainstem lesions were less frequent in fMS (50.8% vs 63.2% in sMS patients, p=0.039). 1st degree relatives of fMS patients were more often diagnosed with Hashimoto’s (10.3% vs 3.3% in sMS relatives, p=0.02). HLA-DRB1*15 frequency was significantly increased in both sMS and fMS subgroups, compared to HC (34.6% & 32.1% vs 16.7% respectively, p=0.002), while HLA-DRB1*11 was significantly decreased only when comparing sMS with HC (30.8% vs 52%, p=0.002). Conclusions: fMS appears to differ from sMS in terms of lesion distribution. AAO observations could either be real or due to an ‘increased vigilance’ bias in fMS. Allelic distribution findings suggest that HLA polymorphisms are not the most important genetic risk factors for developing fMS, but rather their co-aggregation with multiple non-HLA genetic variations.