[Show abstract][Hide abstract] ABSTRACT: To test the hypothesis that predisposition to childhood herpes simplex virus (HSV) type 1 encephalitis (HSE) may be determined in part by human genetic factors.
A genetic epidemiologic survey of childhood HSE (onset at age 3 months to 15 years) over a 20-year period (1985-2004) was conducted throughout France (comprising 29 university hospital neuropediatric centers). A total of 85 children fulfilled the diagnostic criteria for inclusion. Family and personal histories were obtained by face-to-face interview for 51 patients.
No familial cases of HSE were identified in our survey; however, a high proportion (20%) of the children interviewed had a relevant family history: parental consanguinity (12% of patients), early-onset herpetic keratitis in a first-degree relative (6%), or both (2%). The narrow window of high susceptibility to HSE before age 3 years (62% of patients) further indicates that predisposition to HSE is tightly age-dependent.
This survey suggests that childhood HSE, although sporadic, may result from Mendelian predisposition (from autosomal recessive susceptibility in particular), at least in some children. There likely is incomplete penetrance, however, which may reflect, at least in part, the impact of age at the time of HSV-1 infection.
Full-text · Article · Oct 2010 · The Journal of pediatrics
[Show abstract][Hide abstract] ABSTRACT: Herpes simplex virus-1 (HSV-1) encephalitis (HSE) is the most common form of sporadic viral encephalitis in western countries.
Its pathogenesis remains unclear, as it affects otherwise healthy patients and only a small minority of HSV-1–infected individuals.
Here, we elucidate a genetic etiology for HSE in two children with autosomal recessive deficiency in the intracellular protein
UNC-93B, resulting in impaired cellular interferon-α/β and -λ antiviral responses. HSE can result from a single-gene immunodeficiency
that does not compromise immunity to most pathogens, unlike most known primary immunodeficiencies. Other severe infectious
diseases may also reflect monogenic disorders of immunity.