Genetic counseling and presenilin-1 Alzheimer's disease: "Research Family" members share some thoughts.

Genetic counseling is a 2-way street between counselor and the counseled. In this article, both share experiences gained through more than 25 years of searching for the gene, finding the presenilin-1 Alzheimer's disease gene, and waiting for a cure. "Research Families" made research models a reality. Few family members requested presymptomatic testing.

Genetic aspects of Alzheimer's disease, Pick's disease, and other dementias.

Although genetic testing is available for some degenerative diseases, in most types of dementia, both genetic and environmental factors are involved. Overall, dementing diseases can be either sporadic or inherited, and in general, the earlier the onset, the more likely a disease is to be inherited. Before genetic testing is performed, the ethical issues, such as the effect the tests might have on asymptomatic children, should be considered. The ethical use of DNA samples in research is another genetic testing issue to be considered.

Caring for children of parents with frontotemporal degeneration: a report of the AFTD Task Force on Families With Children.

The Association for Frontotemporal Degeneration (AFTD) organized a 7-person Task Force on Families With Children to explore the concerns of families when a parent of young children or teens is diagnosed with FTD. This report summarizes the findings of the task force and highlights the need for additional attention to this topic. The task force conducted a review of related literature and existing resources and compiled issues identified by spouses/partners, teens, and adult children within an affected family. The project confirmed a significant lack of information and support for parents caring for a spouse with FTD and for their children. Recommendations include developing resources and strategies that promote comprehensive family support, including those that build resiliency in the well parent and the children, and strengthen the changing family unit. Avenues for additional research in this area of need in the FTD community are suggested.

Latent class subtyping of attention-deficit/hyperactivity disorder and comorbid conditions.

OBJECTIVE: Genetic studies of attention-deficit/hyperactivity disorder (ADHD) generally use discrete DSM-IV subtypes to define diagnostic status. To improve correspondence between phenotypic variance and putative susceptibility genes, multivariate classification methods such as latent class analysis (LCA) have been proposed. The aim of this study was to perform LCA in a sample of 1,010 individuals from a nationwide recruitment of unilineal nuclear families with at least one child with ADHD and another child either affected or clearly unaffected. METHOD: LCA models containing one through 10 classes were fitted to data derived from all DSM-IV symptoms for ADHD, oppositional defiant disorder, and conduct disorder (CD), as well as seven items that screen for anxiety and depression from the National Initiative for Children's Healthcare Quality Vanderbilt Assessment Scale for Parents. RESULTS: We replicated six to eight statistically significantly distinct clusters, similar to those described in other cross-cultural studies, mostly stable when comorbidities are included. For all age groups, anxiety and depression are strongly related to Inattentive and Combined types. Externalizing symptoms, especially CD, are strongly associated with the Combined type of ADHD. Oppositional defiant disorder symptoms in young children are associated with either conduct disorder or anxiety-related symptoms. CONCLUSIONS: Methods such as LCA allow inclusion of information about comorbidities to be quantitatively incorporated into genetic studies. LCA also permits incorporation of milder but still impairing phenotypes than are allowed using the DSM-IV. Such methods may be essential for analyses of large multicenter datasets and relevant for future clinical classifications. This population-based ADHD classification may help resolve the contradictory results presented in molecular genetic studies.

Prothrombotic factors in children with stroke or porencephaly.

OBJECTIVE: This study compared the frequencies of genetic and functional coagulation abnormalities in children with arterial ischemic stroke or porencephaly with frequencies in previously published studies. METHODS: A series of 59 children (age 0-18 years) with arterial ischemic stroke or porencephaly were referred to the National Institutes of Health. A blood sample, buccal smear sample, questionnaire, and pedigree were requested for each child. Blood samples were analyzed for protein C (PC); protein S; antithrombin (AT); activated PC resistance (APCR); lipoprotein (a) [Lp(a)]; lupus anticoagulant; anticardiolipin antibodies; and the methylenetetrahydrofolate reductase C677T (MTHFR), factor V G1619A, factor II G20210A (PT), plasminogen activator inhibitor-1 4G6755G, and tissue factor pathway inhibitor C536T mutations. The frequency of each coagulation abnormality was compared with published international pediatric stroke case and control rates. RESULTS: At least 1 prothrombotic abnormality was identified in 63% (36 of 57) of children studied, including plasminogen activator inhibitor-1 4G6755G (15 of 56), MTHFR (12 of 56), elevated Lp(a) (12 of 59), APCR (11 of 58), factor V G1619A (5 of 57), PT (3 of 57), PC deficiency (1 of 59), and AT deficiency (1 of 59). The MTHFR mutation, elevated Lp(a), the PT mutation, and AT deficiency rates were similar to rates in cases and more common than control subjects in previously published studies. The rate of children with APCR or multiple abnormalities was higher than in previous pediatric stroke studies. A family history of early thrombosis was identified in one third of the children with a prothrombotic abnormality. CONCLUSIONS: Two thirds of children in this study had at least 1 of the prothrombotic risk factors tested, and several children had multiple risk factors. These results provide additional evidence that prothrombotic abnormalities are common among children with AIS or porencephaly.