Clinical correlations of mutations in the SCN1A gene: from febrile seizures to severe myoclonic epilepsy in infancy.

Mutations in the alpha-subunit of the first neuronal sodium channel gene SCN1A have been described in isolated patients with severe myoclonic epilepsy in infancy or Dravet syndrome and in families with generalized epilepsy with febrile seizures plus. To find phenotype/genotype correlations, we reviewed all published cases of mutations in SCN1A in addition to four new patients reported here. A total of 60 mutations were observed. Approximately 52% (31/60) are truncating mutations correlating with de novo cases of classical Dravet syndrome in 32 of 34 (94%) patients. Missense mutations in the pore-forming part constitute 27% (16/60) and correspond to a classical type in 12 of 16 (75%) patients. Missense mutations in the voltage sensor were present in 12% (7/60) and correlate with a clinical picture ranging from febrile seizures plus to severe myoclonic epilepsy in infancy. Outside these regions missense mutations are rare and account for only 10% (6/60), corresponding mostly with febrile seizures plus. These results illustrate that the clinical spectrum of SCN1A mutations ranges from febrile seizures, febrile seizures plus, over a milder type to the classical form of severe myoclonic epilepsy in infancy, and confirm the clinical experience that severe myoclonic epilepsy in infancy is the most severe form on this spectrum.

Childhood chronic inflammatory demyelinating polyneuroradiculopathy--three cases and a review of the literature.

BACKGROUND: Chronic inflammatory demyelinating polyneuroradiculopathy (CIDP) is an autoimmune disease of the peripheral nervous system, causing demyelination and even axonal degeneration. In children, abnormal gait as a first sign of muscle weakness is a frequent reason to seek medical attention. Diagnosis is made on the basis of clinical characteristics, electromyography and nerve conduction studies, and elevated protein in cerebrospinal fluid. AIMS: We present three new cases of CIDP. The literature was reviewed in order to obtain more information on presentation, outcome and treatment strategies world-wide. RESULTS: The course of disease can be relapsing-remitting or chronic-progressive. From case series it is known that first-line immunotherapy (intravenously administered immunoglobulin, corticosteroids or plasmapheresis) is initially of benefit in most children with CIDP. There is little evidence, however, on second-line therapies as azathioprine, cyclosporine A, mycophenolate mofetil, methothrexate, cyclophosphamide and IFN alpha. Although the outcome of children with CIDP is generally regarded to be good, disease related disability can be severe. CONCLUSION: Childhood CIDP is rare. In general and in comparison to adults, children tend to have a more acute progressive onset, with more severe symptoms. Showing a higher tendency towards a relapsing-remitting course, children often show a better and faster improvement after therapy, and a more favorable outcome. Swift recognition of CIDP and empiric start of treatment are considered important to avoid potentially irreversible axonal damage and associated disability. Response to first-line therapies is usually favorable, however recommendations regarding the choice of second-line therapy can only be made on the basis of current practice described in case reports. Safety and efficacy data are insufficient. The cases described show that trial and error are often involved in finding an optimal treatment strategy, especially in those patients refractory to first-line treatment or with a prolonged course. Clinical experience with immunomodulatory treatment is paramount when treating children with CIDP.