Febrile Convulsions as a Problem in Waiting Times

A simple hypothesis on the occurrence of febrile convulsions is posed. This is (1) that certain children are genetically predisposed, and (2) that for such children, the probability of the first attack occurring in year 1, 2, etc., is essentially constant up to the end of the period during which the attacks can take place. These assumptions lead to a probability model which agrees well with data on age at first attack in the Town of Tecumseh, Mich. It appears that susceptibility does not gradually diminish, but rather disappears abruptly. The calculation yields an estimate of the proportion of children, among those susceptible, who will have at least one attack before they exceed the age of suceptibility. Penetrance of the condition, measured in this way, is nearly complete: 93.8% will have manifested the condition by age 7. The population frequency of the susceptible type of child is found to be 3.90%. If one assumes the simple dominant mode of inheritance of Frantzen et al. to be correct, this estimate of population frequency leads to an estimate of the gene frequency. This is approximately p = 0.02. The homozygote would therefore have a frequency of 4 per 10,000. Some speculations on verifying this theory of inheritance by identifying the homozygote are given. RÉSUMÉ On Émet une hypothÈse simple sur la survenue des convulsions fÉbriles, À savoir (1) que certains enfants sont gÉnÉtiquement prÉdisposÉs et (2) que pour ces enfants la probabilitÉ d'apparition de la premiÈre crise dans la premiÈre, la seconde annÉe, etc. est essentiellement constante jusqu'À la fin de la pÉriode pendant laquelle les crises peuvent survenir. De telles suppositions conduisent ÀÉtablir un modÈle de probabilite qui concorde bien avec les donnÉes sur l'Âge de la premiÈre crise, dans la ville de Techumseh, dans le Michigan. Il en ressort que cette prÉdisposition ne diminue pas progressivement, mais au contraire, disparaÎt brusquement. Les calculs permettent d'estimer la proportion d'enfants prÉdisposÉs qui auront au moins une crise, avant d'avoir dÉpassÉ l'Âge limite de la prÉdisposition. La pÉnÉtrance de cette condition, ainsi ÉvaluÉe, est presque complÈte: 93.8% des enfants auront manifestÉ cette condition À l'Âge de 7 ans. La frÉquence des enfants prÉdisposÉs dans la population est de 3.90%. Si l'on considÈre que le mode d'hÉrÉditÉ dominante simple de Frantzen est valable, cette estimation de la frÉquence dans la population conduit À une Évaluation de la frÉquence du gÈne. Celle-ci est approximativement de p = 0.02; l'homozygote aurait done une frÉquence de 4/10.000. Les possibilitÉs de vÉrifier cette thÉorie des modalitÉs hÉrÉditaires par l'identification de l'homozygote sont discutÉes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65705/1/j.1528-1157.1972.tb05265.x.pd

The “maternal effect” on epilepsy risk: Analysis of familial epilepsies and reassessment of prior evidence

Objective: Previous studies have observed that epilepsy risk is higher among offspring of affected women thanoffspring of affected men. We tested whether this “maternal effect” was present in familial epilepsies, which areenriched for genetic factors that contribute to epilepsy risk.Methods: We assessed evidence of a maternal effect in a cohort of families containing ≥3 persons with epilepsyusing three methods: (1) “downward-looking” analysis, comparing the rate of epilepsy in offspring of affectedwomen versus men; (2) “upward-looking” analysis, comparing the rate of the epilepsy among mothers versusfathers of affected individuals; (3) lineage analysis, comparing the the proportion of affected individuals withfamily history of epilepsy on the maternal versus paternal side.Results: Downward-looking analysis revealed no difference in epilepsy rates among offspring of affectedmothers versus fathers (prevalence ratio 1.0, 95% CI 0.8, 1.2). Upward-looking analysis revealed more affectedmothers than affected fathers; this effect was similar for affected and unaffected sibships (odds ratio 0.8, 95%CI 0.5, 1.2) and was explained by a combination of differential fertility and participation rates. Lineage analysisrevealed no significant difference in the likelihood of maternal versus paternal family history of epilepsy.Interpretation: We found no evidence of a maternal effect on epilepsy risk in this familial epilepsy cohort.Confounding sex imbalances can create the appearance of a maternal effect in upward-looking analyses andmay have impacted prior studies. We discuss possible explanations for the lack of evidence, in familialepilepsies, of the maternal effect observed in population-based studie

Paternal and maternal influences on differences in birth weight between Europeans and Indians born in the UK.

BACKGROUND: Ethnic groups differ significantly in adult physique and birth weight. We aimed to improve understanding of maternal versus paternal contributions to ethnic differences in birth weight, by comparing the offspring of same-ethnic versus mixed-ethnic unions amongst Europeans and South Asian Indians in the UK. METHODOLOGY AND PRINCIPAL FINDINGS: We used data from the UK Office for National Statistics Longitudinal Study (LS) and the Chelsea and Westminster Hospital (CWH), London. In the combined sample at all gestational ages, average birth weight of offspring with two European parents was significantly greater than that of offspring with two Indian parents [Δ = 344 (95% CI 329, 360) g]. Compared to offspring of European mothers, the offspring of Indian mothers had lower birth weight, whether the father was European [Δ = -152 (95% CI -92, -212) g] or Indian [Δ = -254 (95% -315, -192) g]. After adjustment for various confounding factors, average birth weight of offspring with European father and Indian mother was greater than that of offspring with two Indian parents [LS: Δ = 249 (95% CI 143, 354) g; CWH: Δ = 236 (95% CI 62, 411) g]. Average birth weight of offspring with Indian father and European mother was significantly less than that of offspring with two European parents [LS: Δ = -117 (95% CI -207, -26) g; CWH: Δ = -83 (-206, 40) g]. CONCLUSIONS/SIGNIFICANCE: Birth weight of offspring with mixed-ethnic parentage was intermediate between that of offspring with two European or two Indian parents, demonstrating a paternal as well as a maternal contribution to ethnic differences in fetal growth. This can be interpreted as demonstrating paternal modulation of maternal investment in offspring. We suggest long-term nutritional experience over generations may drive such ethnic differences through parental co-adaptation

Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition

Collateral fattening refers to the process whereby excess fat is deposited as a result of the body’s attempt to counter a deficit in lean mass through overeating. Its demonstration and significance to weight regulation and obesity can be traced to work on energy budget strategies in growing mammals and birds, and to men recovering from experimental starvation. The cardinal features of collateral fattening rests upon (i) the existence of a feedback system between lean tissue and appetite control, with lean tissue deficit driving hyperphagia, and (ii) upon the occurrence of a temporal desynchronization in the recovery of body composition, with complete recovery of fat mass preceeding that of lean mass. Under these conditions, persistent hyperphagia driven by the need to complete the recovery of lean tissue will result in the excess fat deposition (hence collateral fattening) and fat overshooting. After reviewing the main lines of evidence for the phenomenon of collateral fattening in body composition autoregulation, this article discusses the causes and determinants of the desynchronization in fat and lean tissue recovery leading to collateral fattening and fat overshooting, and points to their significance in the mechanisms by which dieting, developmental programming and sedentariness predispose to obesity

Whole Brain Size and General Mental Ability: A Review

We review the literature on the relation between whole brain size and general mental ability (GMA) both within and between species. Among humans, in 28 samples using brain imaging techniques, the mean brain size/GMA correlation is 0.40 (N = 1,389; p < 10−10); in 59 samples using external head size measures it is 0.20 (N = 63,405; p < 10−10). In 6 samples using the method of correlated vectors to distill g, the general factor of mental ability, the mean r is 0.63. We also describe the brain size/GMA correlations with age, socioeconomic position, sex, and ancestral population groups, which also provide information about brain–behavior relationships. Finally, we examine brain size and mental ability from an evolutionary and behavior genetic perspective