Psychiatric disorders in clinical genetics II: Individualizing recurrence risks.
ABSTRACT This is the second article of a two-part professional development series on genetic counseling for personal and family histories of psychiatric disorders. It is based on an Educational Breakout Session presented by The Psychiatric Special Interest Group of the National Society of Genetic Counselors at the 2006 Annual Education Conference. While the first article in this two part series dealt with addressing family histories of psychiatric disorders in clinical practice, the following discussion deals with the generation and provision of individualized recurrence risks for psychiatric disorders, based on empiric risk data. We present four cases that illustrate important components of and process for generating individualized risk assessment for family histories of psychiatric disorders.
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ABSTRACT: Most new mutations are observed to arise in fathers, and increasing paternal age positively correlates with the risk of new variants. Interestingly, new mutations in X-linked recessive disease show elevated familial recurrence rates. In male offspring, these mutations must be inherited from mothers. We previously developed a simulation model to consider parental mosaicism as a source of transmitted mutations. In this paper, we extend and formalize the model to provide analytical results and flexible formulas. The results implicate parent of origin and parental mosaicism as central variables in recurrence risk. Consistent with empirical data, our model predicts that more transmitted mutations arise in fathers and that this tendency increases as fathers age. Notably, the lack of expansion later in the male germline determines relatively lower variance in the proportion of mutants, which decreases with paternal age. Subsequently, observation of a transmitted mutation has less impact on the expected risk for future offspring. Conversely, for the female germline, which arrests after clonal expansion in early development, variance in the mutant proportion is higher, and observation of a transmitted mutation dramatically increases the expected risk of recurrence in another pregnancy. Parental somatic mosaicism considerably elevates risk for both parents. These findings have important implications for genetic counseling and for understanding patterns of recurrence in transmission genetics. We provide a convenient online tool and source code implementing our analytical results. These tools permit varying the underlying parameters that influence recurrence risk and could be useful for analyzing risk in diverse family structures.The American Journal of Human Genetics 09/2014; 95(4). DOI:10.1016/j.ajhg.2014.08.010 · 10.99 Impact Factor
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ABSTRACT: Despite being the most common congenital facial anomaly, little is understood about the genetic contribution to isolated clefts of the lip with or without cleft palate (CL/P). 'OzCleft', a family-based genotype/phenotype study, is investigating this further. Participation for families involves various clinical investigations of the child with the cleft, and their unaffected sibling(s) and parents. Informal feedback from individuals involved in OzCleft suggested that participation in this research programme had benefits for families. Taking a qualitative approach, this study sought to investigate this hypothesis further. Semi-structured in-depth interviews were conducted with nine parents who had participated in OzCleft. All parents described participation as a positive experience for themselves and their families. Perceived benefits included a greater appreciation of the cleft treatment experience by unaffected family members. Being involved in a genetic study raised issues for parents regarding the cause of clefting in their child. While some parents found the possibility of a genetic component reassuring, it also raised questions about the potential implications for future generations. Parents were largely unsure about how to communicate this information to their children and the predictive value of this information. This study suggests a lack of genetic understanding and/or perceived value of genetic information by parents of children with CL/P that, in turn, highlights the need for increased support from genetic health professionals in this area.Journal of community genetics 02/2014; DOI:10.1007/s12687-014-0183-3
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ABSTRACT: In the last decade, major advances have been made in our understanding of the genetic basis of epilepsy. Genetic testing for over two dozen epilepsy-related genes is now clinically available, and healthcare providers who manage patients with epilepsy are faced with incorporating genetic information into their assessment and treatment plans. Although the clinical applications of genetic test results in the setting of epilepsy may be somewhat limited, an argument for the utility of testing can be made based upon the potential impact on treatment options, the ability to provide prognostic information, and the psychological, medical, and reproductive implications for patients and their family members. Clinicians who incorporate genetic testing into their evalua-tion of patients with epilepsy must be knowledgeable about epilepsy phenotypes and epilepsy genes, have expertise in eliciting a genetic family history that encompasses not only epilepsy but a broader range of relevant medical conditions, and possess a thor-ough understanding of genetic testing methods and outcomes. Given the complexity of genetic test results, it is crucial that informed consent to discuss the risks, benefits, and limitations of genetic testing take place with patients prior to testing. In addi-tion, many patients may benefit from genetic counseling to discuss testing options or results, address family impact or reproductive issues, and obtain access to support resources.