Investigators in Genetics, Pediatrics, Neurology, and Immunology, at Mansoura Un., Mansoura, Egypt found a gene frequency of 0.284 (c.f. 0.093 in controls) and a highly significant association between HLA-B5 antigen and febrile convulsions in 39 patients compared to 380 healthy controls. The high frequency of HLA-B5 antigen (48.7 in patients c.f., 17.6 in controls) reflected a significantly high relative risk and indicated that children having antigen B5 are 4.4 times more susceptible to febrile convulsions than those without that antigen. The means of IgA (89 mg%) and E-rosette (54%) were significantly low c.f. controls (151 and 64, respectively). The authors suggest that the genetic control of febrile convulsions is in linkage disequilibrium with HLA-B5, low IgA and low total T-cells and that this altered immune function may predispose to acute infections and high fever which precipitate the febrile convulsions. [1]

COMMENT: Ehrengut W and Ehrengut J [2] found a lack of immunoglobulins beta-2A and beta-2M and a reduction of gamma globulin in 4 of 6 patients and postulated a weakness of defense mechanisms against infection as a possible cause of febrile convulsions. This report was the first and only reference to hypoimmunoglobulinemia cited in the monograph Febrile Convulsions 1968 MacMillan, N.Y., which included a review of world literature published in English and foreign languages. Isaac et al [3] reported low serum IgA in children with febrile convulsions and Grob and Herold [4] and others have found IgA deficiency among epileptics receiving anticonvulsants, especially hydantoins (see Hafez et al).

The multifactorial inheritance of febrile seizures is alluded to in the 6th annual Merritt-Putnam Symposium [5]. Siblings have approximately a 8-12% risk of alio having febrile seizures. If the index child and one parent are affected, the risks to siblings are 30-40% (50% if both parents are affected). A high proportion of probands and their siblings develop EEG abnormalities 3-5 years after the febrile seizure, including generalized spike-and-wave and a photoconvulsive response (Hauser et al 1985; Millichap, 1968).