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The decisive conclusions to be drawn from the available epidemiological data, mostly geography and prevalence, of MS are: (1) a north-south (as well as west-east in the United States) gradient exists independent of genetic/racial factors; (2) major differences in prevalence occur in the absence of latitude differences; (3) individuals from the same ethnic derivation have either similar prevalence rates or very different prevalence rates in widely separated geographical areas and (4) specific resistant isolates are shown to exist regardless of latitude. Existing information leads to the almost inescapable conclusion that the epidemiology of MS cannot be explained by any single known environmental or genetic factor(s) in isolation. A combination of a heterogeneous distribution of both genetic and environmental factors appears to be required to explain the available data on MS.

The amyloid precursor protein (APP) gene codes for the precursor to the beta-protein found in the amyloid deposits of Alzheimer disease (AD). Recently Goate et al. identified in codon 717 of this gene a missense mutation which segregates with AD in a familial AD (FAD) kindred. The same mutation was also found in affected subjects from a second FAD family but not in other FAD families or in normal controls. The following work was undertaken to determine the frequency of the codon 717 mutation in FAD and nonfamilial AD cases and in normal controls. We tested 76 FAD families, 127 "sporadic" AD subjects, 16 Down syndrome cases, and 256 normal controls for this mutation, and none were positive. We also tested for the APP codon 693 mutation associated with hereditary cerebral hemorrhage with amyloidosis-Dutch type, for PRIP gene missense mutations at codons 102, 117, and 200, and for the PRIP insertion mutations which are associated with Creutzfeld-Jakob disease and Gerstmann-Straussler Scheinker syndrome. No examples of these mutations were found in our population. Thus these APP and PRIP mutations are rare in both FAD and nonfamilial AD.

Since more and more women in developed countries are delaying childbearing to an older age, it is important to find out whether birth defects, other than those resulting from chromosomal anomalies, are related to maternal age. We have studied all 26,859 children with birth defects of unknown aetiology identified among 576,815 consecutive livebirths in British Columbia. All these cases' records were linked with provincial birth records to allow determination of maternal age at birth. We excluded children with chromosomal anomalies and those with other birth defects of known aetiology. Only 3 of the 43 birth defect categories studied showed significant maternal-age-specific trends: there were decreasing linear trends with maternal age for patent ductus arteriosus (chi 2 = 36.65, 1 df, p less than 0.01) and hypertrophic pyloric stenosis (chi 2 = 4.90, 1 df, p less than 0.05) and a bell-shaped curve (risk increasing to maternal age 30 then falling) for congenital dislocatable hip/hip click. The findings from this population-based analysis of no association between the incidence of birth defects of unknown aetiology and advancing maternal age should be reassuring to healthy women who opt to delay childbearing.

British Columbia (B.C.) provides an excellent opportunity to study the accuracy of assigning Underlying Cause of Death (UCOD) in Down syndrome. The study was designed to evaluate the effect of inappropriate interpretation of guidelines for completing the death certificate. All B.C. livebirths identified as having Down syndrome during the period 1952-1981 were collected from the records of the B.C. Health Surveillance Registry. Of the 1,337 affected individuals identified, 324 (24.2%) had died. The death certificates on these individuals were reviewed to assess from the information on the death certificate whether the underlying cause of death appeared to have been assigned in accordance to World Health Organization coding guidelines. The UCOD appeared to be assigned appropriately for 165/315 cases (52.4%). It is possible that in the situation where an easily recognizable condition such as Down syndrome is present, the need to identify the actual UCOD may be viewed as less urgent compared with cases where an apparently "normal" individual dies.

Once diagnosed to have MS, relatives of persons who have been previously diagnosed frequently ask whether their disease course will follow that of their relative(s) with MS. The present study compared the following clinical manifestations of MS among 43 index cases and 47 of their relatives, all of whom were diagnosed to have MS and regularly attended the MS Clinic in Vancouver, British Columbia: (i) age of onset of MS, (ii) clinical course, (iii) lesion site(s) and (iv) initial symptom(s) of MS. The results from the present study are preliminary because of the small size of the study group. However, these data suggest that apart from possibly age of onset between sibling pairs, the clinical manifestations of MS are not correlated among relatives who are assessed according to the same methodology. This is significant for counselling newly diagnosed relatives of longstanding MS patients.

Life expectancy in Down syndrome was calculated to 68 years, using data for 1610 Down syndrome liveborn individuals among over 1.5 million consecutive British Columbia livebirths. Overall, although survival is significantly poorer than for the general population, over half of Down syndrome individuals can be expected to survive into their fifties, and 13.5% will still be alive at age 68. The data are presented as a life table, a practical format for the clinician and planner.

Reports of an apparent decline in the incidence of neural tube defects (NTDs) have come from various parts of the world. If these findings are consistent they would have an important impact on prenatal diagnosis and on screening programs. The incidence of NTDs over a 10-year period was examined in British Columbia, a province that has a population-based health surveillance registry through which there is virtually complete ascertainment of liveborn infants with NTDs. The results showed a significant decrease in incidence only for stillborn infants with anencephaly. The increased use of ultrasonography and the subsequent termination of pregnancies in which the fetus has been found to have anencephaly may explain this observation.

There is little available literature on survival data in the form of lifetables for babies born with anencephaly. These data would be valuable in advising parents, who often request very specific information on the length of time their child might survive. Survival is examined for a cohort of anencephalic infants in a well-defined population. Sex-specific survival tables are given, since these are the most practical to use for counselling purposes. These data show that over 40 percent of liveborn anencephalic infants (51% males; 34% females) survive longer than 24 hours, and of these, 5 percent are still alive on the seventh day. Data also are presented on the types of malformations observed in addition to anencephaly.

A family with familial Alzheimer's disease (FAD) inherited as an apparent autosomal dominant trait is presented. Twelve individuals (6 females; 6 males) in 4 generations were affected. The disease had its onset in the late 30's, early 40's with death by age 50. Although FAD which appears to be transmitted as an autosomal dominant trait is relatively rare, such families must be identified and carefully counselled with respect to recurrence risks for subsequent generations. In this family, there are currently 20 members of Generation IV, aged 15-37, and 9 members of Generation V, aged 1-11. The majority of these individuals appear to have a 50% risk for developing this disease.

To look at the underlying cause of death (U.C.O.D.) data for Down syndrome (DS), we studied 324 DS individuals who died out of a total of 1,337 DS births occurring in 1,066,508 consecutive live births during the years 1952-81 inclusive. U.C.O.D. rates, separated into ICD-9 classifications, for the DS population were compared with those of the age-matched general population. In general, an individual with DS is significantly more likely to die than the age-matched general population over all ages studied up to age 30. The greatest absolute likelihood of dying is under 1 year, but the age group with the greatest relative risk of dying (17.2) is very definitely between ages 1-9. In order, the three categories for causes of death in DS with the greatest relative risk are congenital anomalies, circulatory system, and respiratory system.