Genetic ResearchPediatric Nursing: The State of

the Science

Janet K. Williams, PhD, RN, FAAN

MNRS 2009

Genetic Research: Pediatrics

• Genetic discoveries

• Research issues

• Research and children

• Knowledge gaps

Genetic Discoveries

• Traditional categories– Chromosomal abnormalities– Monogenic- Mendelian disorders– Multifactorial/polygenic disorders– Mitochondrial disorders

Genetic Discoveries

• Single gene– Mutations in one gene- ex. Cystic fibrosis

• >1600 known mutations• 5 mutation classes according to effect on CFTR

protein• Some mutations associated with clinical

manifestations, others less predictable

Genetic Discoveries

• Disorders in genome architecture-Mutations associated with dysmorphic syndromes• Sporadic inheritance• ex-microdeletion syndromes- DiGoerge, syndrome,

Williams syndrome

Genetic Discoveries

• Insights into taxonomy of human disease– Distinct forms of a condition- ex.diabetes

mellitus– Labeling account for mechanisms and

pathways of a disease rather than symptom description

– May resolve questions relating to variable symptoms, progression, response to therapy

Genetic Discoveries

• Genome wide association studies– Scan genome [not just the coding regions] to

generate hypotheses about genome regions associated with specific phenotypes

– Allow study of pathways from gene expression to common diseases or traits

– Association accepted when• Large effect• Replicated• Made sense

Genetic Discoveries

• GWAS- limitations• Small odds ratios• May need hundreds of associations needed to

account for heritability of a common disorder• Unknown environmental factors

• Current pediatric examples (PubMed)• GWAS and ADHD (ages 5-17, and parents)• GWAS and bone mineral density in childhood

(N=1518children in longitudinal child health study)

Genetic Discoveries

• Areas of relevance to children’s health – in press issue Journal of Pediatric Psychology

• 6 papers- parent decision making with new genetic testing, health care delivery systems, research on behavioral phenotypes (eating disorders), parental attitudes about genetic testing of children

– In press issue Journal of Pediatric Nursing• 3 papers- acquisition of concept of genetics,

therapy response in cancer and mental illness

Genetic Discoveries

• Areas of relevance to child health– In press issue Biological Research for Nursing

• Prior articles include clinical diagnoses for which children may be at risk based on family history- ex. cardiac arrythmias

– 2008 volume 17 special issue Psycho-oncology

• 14 papers-decision making, family communication, health behaviors

• Excellent future research discussion

Genetic Discoveries

• Genetic ‘information’-clarify terminology– Can refer to a person’s DNA and the

instructions in that DNA– Can refer to what is communicated by health

professionals regarding one’s risk for disease or risk to have offspring with a disease

Genetic Discovery Resources

• UI online courses– http://www.continuetolearn.uiowa.edu/ccp/de/regform.htm

• Postdoctoral fellowships– T32 funded- UI, U Pittsburgh, NIH

• NINR SGI– http://www.ninr.nih.gov/Training/TrainingOpportunitiesIntramural/

SummerGeneticsInstitute/

• NHGRI Summer Workshop in Genomics– http://www.genome.gov/10000217

• ISONG annual conference Oct 16-19– http://www.isong.org/

Funding opportunities

• NINR

• NHGRI/ELSI

• ANF

• Sigma Theta Tau chapters

Research issues

• Categories of nursing research in genetics and pediatrics– Studies are about children but children are not

the subjects– Children are members of families in studies– Children are subjects in studies

Research issues

• Theoretical/conceptual frameworks– Clinical problem– Theoretical relevance

• Research purpose– Response to having specific genetic

characteristics, family issues• Ex. Communication of risk, clinical decision

making, quality of life, emotional status, health behaviors

Research issues

• Human subjects concerns– Protection of children as a vulnerable

population– Sensitive topics– Parental permission, children assent

Research issues

• Population definition– Genetic characteristics of population as

inclusion criteria• Genetic heterogeneity in diagnosis?

• Methods– Appropriate measures for age groups– Sample size with rare conditions

About children

• Metcalfe, 2009– Role of genetics- population clients at end of life– Framework- professional practice quality evaluation– Purpose- nurse perceptions of importance and

confidence in caring for children with genetic conditions

– Sample- n=100 hospice nurses in UK– Methods- questionnaire with 4 scenarios– Findings-1 child/month, important, supporting child

and family is demanding, nurses need support

Study of family issue

• Clarke, 2008– Role of genetics- population women with BRCA1/2

mutation– Framework-clinical disclosure– Purpose-communication of risk information to offspring– Sample- 24 women with BRCA1/2 mutation in a

therapy group, 71% with children ages 2-30,45% with prior cancer diagnosis

– Methods-grounded theory approach– Findings- predisclosure, disclosure, impact of

disclosure phases

Study of family issue

• Norris, 2009– Role of genetics- population women with BRCA1/2

mutation– Framework- clinical response to risk– Purpose- family context of communication and

decision– Sample- 5 women with BRCA1/2 mutation, 3

husbands, 6 daughters, 3 sons (ages 15-25)– Methods- descriptive qualitative– Findings- disclosure varied, with some uncertain how

or when, children learn informally of risk

Study of children

• Christian, 2006– Role of genetics- population children with CF– Framework-Self management-development– Purpose- intervention for day to day disease management– Sample-n=116 children ages 8-12 with mild CF– Methods- randomized. E=finding out about dx, explaining

CF related differences, teasing, keeping up with peers. Home visit and small group.

– Findings E > C scores on impact of illness, < lonely, >global self worth. Functional health and physiologic health n.s.

Study of children

• Iles-2008– Role of genetics- population youth with CF– Framework- transition services and development – Purpose program evaluation in transitional clinic– Sample n=50,13-24 year old– Methods-interview, some completed a QOL measure– Findings- nurses were like family- hesitant to share

worries about future with nurses

Study of family issue

• Gallo, 2008– Role of genetics-population children with single gene

disorders– Framework- clinical parental concerns– Purpose- parental concerns re privacy, disclosure,

employment, insurability– Sample- n=142 parents in 86 families, children with

scd, cf, pku, nf, hemoplilia, thalassemia, Marfan syndrome

– Methods- semi-structured interview, thematic analysis– Findings- less concern re privacy than other topics

Study of children

• Giarelli, 2008– Role of genetics- population youth with MS, parents, hcp

– Framework-Transition to self management

– Purpose-identify basic psychologic issue in transition to self management

– Sample- n=37 children with MS ages 14-21, 16 young adults with MS ages 22-34, 39 parents (20 w MS), 16 hcp

– Methods-questionnaires and interviews

– Findings- becoming fit and fitting in- a survival goal. changes in knowledge, attitudes, behavior by all

Study of children

• Sparbel, 2008– Role of genetics- population teens with

parent/grandparent with HD– Framework- development– Purpose-explore experiences of teens living in HD

families – Sample- n=32 teens ages 14-18– Methods-descriptive qualitative, focus groups– Findings- watching & waiting, alone in the midst of

others, family life is kind of hard, having to be like an adult

Study of children

• Williams, in press– Role of genetics- population teens with

parent/grandparent with HD– Framework- Caregiving, development0– Purpose- examine caregiving by teens– Sample- n=24 teens ages 14-18– Methods-descriptive qualitative, focus groups– Findings- tasks and responsibilities, & subjective

burden similar to adult cg; cg in context of personal risk, & decisional responsibility unique to teens

Summary

• Genetic/Genomic pediatric nursing research – Interdisciplinary body of knowledge– Interdisciplinary research teams– Clear definition of genetic aspects of population– Clinical vs. community populations– Multiple site data collection for diversity and sample size– Programs of research extending from descriptive to

experimental designs– Citations available upon request