BackgroundNarcolepsy is a rare neurological sleep disorder especially in children who are younger than 10 years. In the beginning of 2010, an exceptionally large number of Finnish children suffered from an abrupt onset of excessive daytime sleepiness (EDS) and cataplexy. Therefore, we carried out a systematic analysis of the incidence of narcolepsy in Finland between the years 2002–2010.MethodsAll Finnish hospitals and sleep clinics were contacted to find out the incidence of narcolepsy in 2010. The national hospital discharge register from 2002 to 2009 was used as a reference.FindingsAltogether 335 cases (all ages) of narcolepsy were diagnosed in Finland during 2002–2009 giving an annual incidence of 0.79 per 100 000 inhabitants (95% confidence interval 0.62–0.96). The average annual incidence among subjects under 17 years of age was 0.31 (0.12–0.51) per 100 000 inhabitants. In 2010, 54 children under age 17 were diagnosed with narcolepsy (5.3/100 000; 17-fold increase). Among adults ≥20 years of age the incidence rate in 2010 was 0.87/100 000, which equals that in 2002–2009. Thirty-four of the 54 children were HLA-typed, and they were all positive for narcolepsy risk allele DQB1*0602/DRB1*15. 50/54 children had received Pandemrix vaccination 0 to 242 days (median 42) before onset. All 50 had EDS with abnormal multiple sleep latency test (sleep latency <8 min and ≥2 sleep onset REM periods). The symptoms started abruptly. Forty-seven (94%) had cataplexy, which started at the same time or soon after the onset of EDS. Psychiatric symptoms were common. Otherwise the clinical picture was similar to that described in childhood narcolepsy.InterpretationA sudden increase in the incidence of abrupt childhood narcolepsy was observed in Finland in 2010. We consider it likely that Pandemrix vaccination contributed, perhaps together with other environmental factors, to this increase in genetically susceptible children.

The unequal expression levels of TTN transcripts in 5 probands suggested severely reduced expression of the frameshift mutated allele, probably through nonsense-mediated decay, explaining the more severe phenotypes. The Iberian TMD mutation may cause a more severe TMD rather than LGMD2J when homozygous. The Finnish patient compound heterozygous for the FINmaj TMD mutation and the novel A-band titin missense mutation showed a phenotype completely different from previously described titinopathies. Our results further expand the complexity of muscular dystrophies caused by TTN mutations and suggest that the coexistence of second mutations may constitute a more common general mechanism explaining phenotype variability.

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Gene amplification using polymerase chain reaction (PCR) was carried out on DNA samples from a total of 92 normal subjects and 52 subjects with myotonic dystrophy (DM) from European and Japanese populations, to determine the copy number of the CTG repeat associated with DM for each group. In the two populations, the number of repeats on normal chromosomes only were compared, as CTG copy number on DM chromosomes was difficult to determine by PCR alone. In this study, normal chromosomes were found which had as many as 35 copies of the repeat, which is larger than the normal range reported previously but still does not overlap with the repeat number associated with DM pathology, which is at least 50 copies. Using data from normal chromosomes from unrelated subjects, the frequencies of five, 11, and 13 copies of the CTG repeat were found to be significantly different between the two populations, with five and 11 copies more commonly seen in the European population and 13 copies in the Japanese population. This difference may be the result of natural divergence of the normal chromosomes between the population groups.

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