Molecularly confirmed pontocerebellar hypoplasia in a large family from Slovakia with four severely affected children.

BACKGROUND: Pontocerebellar hypoplasia type 1 (PCH1) is characterized by a central and peripheral motor dysfunction associated with anterior horn cell degeneration, similar to spinal muscular atrophy (SMA). OBJECTIVES: We analysed three probands (later discovered to be siblings) suspected to have severe SMA, however, not confirmed by genetic test. METHODS: Clinical-exome analysis (Illumina) was performed to identify causative variants, followed by Sanger sequencing confirmation in probands and other 10 family members. RESULTS: Homozygous pathogenic variant c.92G>C (p.(Gly31Ala)) in the Exosome Component 3 (EXOSC3) gene was found in all 3 probands, thus confirming the diagnosis of a severe form of PCH1B. The parents and six siblings were carriers, while one sibling was homozygous for a reference allele. This variant is frequent in the Czech Roma population, where it is considered a founder mutation. Haplotype analysis in this largest reported PCH1B family showed that our patients inherited from their father (of Roma origin) a haplotype identical to that found in the Czech Roma population, thus indicating these alleles have a common origin. CONCLUSION: This EXOSC3 variant is rare among the general population but most likely frequent also among Roma people in Slovakia. PCH1B should be considered for a differential diagnosis in infants manifesting SMA-like phenotype, especially if of Roma origin (Tab. 1, Fig. 1, Ref. 22). Text in PDF www.elis.sk Keywords: pontocerebellar hypoplasia, PCH1B, EXOSC3, SMA plus syndromes, pathogenic sequence variant.

Etiology, Risk Factors and Outcome of 1003 Cases of Infective Endocarditis from a 33-year National Survey in the Slovak Republic: An increasing proportion of elderly patients.

BACKGROUND: Infective endocarditis (IE) is still a significant cause of mortality in European hospitals, despite of the fact, that large nationwide studies were performed in last twenty years and pathogens are well known. The aim of the study was to assess risk factors, mortality, etiology and proportion of elderly patients within a longitudinal nation wide survey of infectious endocarditis in Slovakia. PATIENTS AND METHODS: Etiology, risk factors and outcome of 1003 cases of infective endocarditis (IE) in Slovakia over the last 33 years have been assessed. RESULTS: The majority of IE were caused by Staphylococci (28.3%), 15.6% were due to Viridans streptococci, 10% due to Enterococci, 8.2% by gram-negative bacteria, Acinetobacter baumannii and Pseudomonas aeruginosa, 3.7% by other organisms and 31.0% of all cases were culture negative. The following risk factors were recorded: age > 65 (36.8%), rheumatic fever (15.3%), dental surgery (8.7%), previous non-cardiological surgery (8.2 %), neoplasia (8.1%), diabetes (7.8%), any endoscopy (8.5%) and dialysis (4.6%). All patients were treated with antimicrobials, 507 (51%) also with surgery. Survival rate at day 60 after diagnosis was 88.1% (n=883). Only age >65 (34.3% vs. 49.5%, p=0.045) and persistent bacteremia (with three or more positive blood cultures 15.7% vs. 34.5%, p=0,001) were significantly associated with higher attributable mortality. Concerning risk factors, etiology and therapeutic strategies, rheumatic fever and neoplasia showed decrease in tendency. Dental surgery and tonsillitis were less frequent as well (26.7% vs. 2%, p<0,001 and 16% vs. 1%, p<0.001). There was a significant shift in etiology after 1997: culture-negative endocarditis was surprisingly more frequently observed in the 2007-2017 period than before and represented 10.7% of all cases in 1984-1990 in comparison to 25.1-25.6% in 2007-2010 and 2011-2017. Staphylococci decreased from 48% to 29.6% (2007-2017), but are still major pathogens. Persistent bacteremia (3 or more positive blood cultures 5.3% vs. 24.7%, p<0,001) was less commonly observed within the 1st period (1984-1990) in comparison to 2007-2010. More patients in the 1st period (1984-1990) had embolization complications of IE than in the fifth and sixth period (2007-2017) (76 vs. 16.3% p<0.001). CNS embolization decreased from 14% to less than 5% (p<0.003). Attributable mortality was lower too (26.7% vs. 9.5%, p<0.001) because of increased proportion of cardiac surgery in the treatment of IE in 2007-2017 in comparison to 1984-1990. CONCLUSIONS: Study has showed significant shifts in etiology, risk factors and complications over the observed time periods in Slovakia.