Infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations.

Familial cases of West syndrome have been reported only in Japan. In that study no chromosomal analyses were made. It has been suggested that microarray analysis should be included in the diagnostic evaluation of patients with infantile spasms and developmental delay, when an evaluation for structural brain lesions and metabolic disorders reveal no abnormal findings. We report here the first case of infantile spasms and 15q11.2q13.1 chromosome duplication in two successive generations. The daughter and mother with infantile spasms, and the autistic son had the duplication. The clinical course of infantile spasms was very similar in the mother and daughter. The spasms were primarily considered to be of unknown aetiology. Chromosomal microarray analysis revealed a 6.2 Mb size 15q11.2q13.1 duplication. The duplication belongs to the 15q11q13 duplication syndrome (OMIM 608636) which when maternally derived is characterised by neuro-behavioural disorders like autism, hypotonia, cognitive deficit, language delay and epilepsy. The proportion of patients with unknown aetiology for infantile spasms will decrease when more careful chromosomal studies are made. Our report expands the phenotype of chromosome 15q duplication syndrome and is the first report of this abnormality in two successive generations of infantile spasms.

Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland.

BACKGROUND: Narcolepsy 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. METHODS: All 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. FINDINGS: Altogether 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. INTERPRETATION: A 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.

Primary human herpesvirus-6 infection in the central nervous system can cause severe disease.

Human herpesvirus-6 (HHV-6) infection is common in infancy, and symptoms are usually mild. However, encephalitis and other neurologic complications have been reported. Primary HHV-6 infection has been rarely confirmed in the central nervous system. We studied 21 children with suspected HHV-6 infection, drawn from a prospective, large-scale study of neurologic infections in Finland. Human herpesvirus-6 polymerase chain reaction was performed on cerebrospinal fluid samples, and antibody tests were performed on serum and cerebrospinal fluid. We identified nine children, aged 3 to 24 months, who had HHV-6-specific nucleic acid in cerebrospinal fluid. Primary infection was confirmed by seroconversion of specific antibodies in six, whereas one had a fourfold increase, and one had a fourfold decrease, in the antibody titer supporting recent infection. Generalized and prolonged seizures appeared in six children, four had a rash, four had ataxia, and four had gastroenteritis. All but two had a high fever. At follow-up, four children had evident neurologic sequelae, ataxia, and developmental disability, and needed special education. Primary HHV-6 infection may invade the central nervous system, and can cause neurologic symptoms and potentially permanent disability in children aged