Patterns of inheritance in Irish and Italian families with neural tube defects: comparison between high and low rate areas.

Neural tube defects (NTDs) may result from a genetic susceptibility interacting with environmental exposures occurring early in pregnancy. Current research is concerned with enlarging our understanding of the action of folic acid, a B group vitamin, which has been shown to prevent the occurrence of NTDs in clinical trials. Despite the epidemic waves in the incidence of NTDs and the existence of areas with very high rates, there have been few studies that explored the genetic contribution to NTDs in high rates versus low rate areas. We investigated the genetic epidemiologic factors that occur in NTD families and compared their frequency in a high rate area-Ireland-with a low rate area-Italy. We explored the existence of three features indicative of hereditary factors and found that all three factors were higher in Ireland than in Italy. These factors were (i) sibling recurrence risk (3.3% vs 1.6%; p = 0.2), (ii), other malformations in siblings (11.5% vs 3.3%; p < 0.001) and (iii) average number of children in mothers' families vs fathers' families (average difference in Ireland 1.0 vs 0.4 in Italy; p < 0.1). These results support the motion that geographic differences in occurrence of NTDs are due at least in part to differing prevalences of genetic susceptibility factors. Further epidemiological and molecular studies are needed to confirm this observation. In addition, studies of the interactions between environmental agents and genetic susceptibility will be important in determining their relative contributions.

Multigeneration maternal transmission in Italian families with neural tube defects.

Periconceptional vitamin supplementation with folate prevents about three-quarters of expected cases of neural tube defects (NTDs) in clinical trials. However, vitamin action may be regulated at the level of the gene, and individual susceptibility to environmental agents, including dietary components, also may be under genetic control. We investigated the presence of familial factors in a retrospective case control study of neural tube defects in Genoa, Italy. Cases included all patients treated at a single pediatric neurosurgical service. Controls matched on age and sex came from the same hospital. We found strong evidence for the contribution of genetic factors in this study. There was an excess risk of 14 for the occurrence of NTDs in first-degree relatives compared to controls (P < .0005). There was no difference in sex ratio in any group of relatives, but maternal grandparents of children with a high spinal lesion had 14% fewer off-spring than paternal grandparents (P < .005), possibly because of excess miscarriages. Our study is the first to show complex patterns of inheritance in spina bifida families affecting three generation in one clinical subgroup and preferentially on the mother's side. These results support a role for genomic imprinting and highlight the value of multidisciplinary epidemiologic and clinical studies that include multiple generations. New studies incorporating dietary and genetic approaches will help clarify and extend these findings.

Cytogenetics of the tissue involved in neural tube defects.

Cytogenetic techniques were used to study the tissue involved in neural tube defects. Eighteen patients have been evaluated and no specific alterations have been detected. We conclude that, whatever are the mechanisms that lead to neural tube defect, their origins must be searched for at the molecular level.

[The Bartter-like syndrome in 2 twins]. / Sindrome Bartter-like in due gemelli.

We present a case of two twins, admitted to our department at the age of 9 years and 9 months for poor stature-ponderal growth. Hematochemical tests showed hypokalemia, hypomagnesemia, metabolic alkalosis, renin increase, normal aldosterone values, hypocalciuria. Arterial pressure values were normal in both patients. Renal hypokalemia with metabolic alkalosis was hypothesized and therefore tubular functions during diuresis induced by intravenous 5% dextrose in water were evaluated and fractionated tubular resorption values of chlorides were identified. The two patients presented many characteristics typical of Bartter syndrome (suggestive facies, short stature, hypokalemia, metabolic alkalosis, renin increase, decreased chloride resorption) and of Gitelman syndrome (late onset, few symptoms, hypomagnesemia, hypocalciuria, normal renal concentration). The definition "Bartter-like syndrome" seems to be more suitable for these patients, since it can include all the clinical characteristics and biochemical anomalies observed.

[Juvenile fibromyalgia syndrome: 2 clinical cases]. / Sindrome fibromialgica giovanile: due casi clinici.

We report two cases (F. 11 years, M. 7 years) with juvenile fibro-myalgic syndrome, diagnosed because of the presence of musculo-skeletal pain, tender points and associated symptoms, and after exclusion of any other known etiology. Both patients improved after treatment with antidepressant serotoninergic (amitriptyline, trazodone).