Age-dependent Mendelian predisposition to herpes simplex virus type 1 encephalitis in childhood.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Abel
Laurent
L
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM (National Institute of Health and Medical Research), Paris, France. laurent.abel@inserm.fr
Plancoulaine
Sabine
S
Jouanguy
Emmanuelle
E
Zhang
Shen-Ying
SY
Mahfoufi
Nora
N
Nicolas
Nathalie
N
Sancho-Shimizu
Vanessa
V
Alcaïs
Alexandre
A
Guo
Yiqi
Y
Cardon
Annabelle
A
Boucherit
Soraya
S
Obach
Dorothée
D
Clozel
Thomas
T
Lorenzo
Lazaro
L
Amsallem
Daniel
D
Berquin
Patrick
P
Blanc
Thierry
T
Bost-Bru
Cécile
C
Chabrier
Stéphane
S
Chabrol
Brigitte
B
Cheuret
Emmanuel
E
Dulac
Olivier
O
Evrard
Philippe
P
Héron
Bénédicte
B
Lazaro
Leila
L
Mancini
Josette
J
Pedespan
Jean-Michel
JM
Rivier
François
F
Vallée
Louis
L
Lebon
Pierre
P
Rozenberg
Flore
F
Casanova
Jean-Laurent
JL
Tardieu
Marc
M
D000212:Acyclovir / Q000627:therapeutic use; D000293:Adolescent; D000367:Age Factors; D017668:Age of Onset; D000998:Antiviral Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D020803:Encephalitis, Herpes Simplex / Q000188:drug therapy / Q000235:genetics* / Q000821:virology*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D012307:Risk Factors; D018139:Simplexvirus; D051196:Toll-Like Receptor 3 / Q000235:genetics*; D055815:Young Adult
D000998:Antiviral Agents; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D000212:Acyclovir