11.2.R1 Recommendation
Echocardiography for at-risk adults
- Strength of recommendation:
- Conditional for intervention
- Level of evidence:
- Very low
How the strength and level of evidence are graded
What the strength of a recommendation means
The strength of a recommendation reflects the extent to which a guideline panel is confident that desirable effects of an intervention outweigh undesirable effects, or vice versa, across the range of patients for whom the recommendation is intended.
Strong for (↑↑) or against (↓↓) intervention
For patients: Most individuals in this situation would want the recommended course of action and only a small proportion would not.
For clinicians: Most individuals should receive the recommended course of action.
Conditional for (↑) or against (↓) intervention
For patients: The majority of individuals in this situation would want the suggested course of action, but many would not.
For clinicians: Recognize that different choices will be appropriate for different patients, and that you must help each patient arrive at a management decision consistent with her or his values and preferences.
Neither intervention nor comparison (—)
The panel did not recommend for or against the intervention.
Source: GRADE Handbook, section 6.1, Table 6.1 (GRADE uses “weak” and “conditional” interchangeably).
For the rating of the strength of the recommendation, in addition to evidence from studies in FRDA, evidence from like conditions, clinical experience and expert consensus are taken into account when published evidence is not available.
The level of evidence is based on published evidence from studies in FRDA. If there is no published evidence in FRDA, evidence from other like conditions or clinical expertise may have been used to make the recommendation – this is graded as ‘very low’ or in some cases ‘low’ level evidence. See the table below for an explanation of the symbols used to grade recommendations.
| Strength of recommendation | Symbol | Level of evidence | Symbol |
| Strong for intervention | ↑↑ | High | ⨁⨁⨁⨁ |
| Conditional for intervention | ↑ | Moderate | ⨁⨁⨁◯ |
| Neither intervention nor comparison | — | Low | ⨁⨁◯◯ |
| Conditional against intervention | ↓ | Very low | ⨁◯◯◯ |
| Strong against intervention | ↓↓ |
We suggest that adult siblings of a person with Friedreich ataxia, who do not wish to have genetic testing to confirm whether or not they have Friedreich ataxia, be offered echocardiography to see if they have any cardiac signs that may require treatment.
Question
Should offering echocardiograms versus no echocardiograms be used for untested adult siblings of people with Friedreich ataxia?
Justification
Cardiac involvement is the main cause of mortality in Friedreich ataxia (6) and can be treated to reduce the chance of cardiac morbidity and mortality. Offering echocardiography can enable a person who does not wish to have genetic testing to avoid possible definitive diagnosis of Friedreich ataxia, while at the same time maintaining safety. Identification of cardiac abnormality by echocardiography may lead to treatment that can reduce morbidity and mortality. Normal echocardiography may result in reduced anxiety for the individual.
Subgroup consideration
This recommendation is for untested adult siblings of individuals with Friedreich ataxia.
Evidence to recommendation table (PDF)
Part of 11.2 Management of testing for adult siblings of a person with Friedreich ataxia
References (18)
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2. Candayan A, Yunisova G, Cakar A, Durmus H, Basak AN, Parman Y, et al. The first biallelic missense mutation in the FXN gene in a consanguineous Turkish family with Charcot-Marie-Tooth-like phenotype. Neurogenetics. 2020;21(1):73-8.
3. Delatycki MB, Paris DB, Gardner RJ, Nicholson GA, Nassif N, Storey E, et al. Clinical and genetic study of Friedreich ataxia in an Australian population. Am J Med Genet. 1999;87(2):168-74.
4. Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, et al. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med. 1996;335(16):1169-75.
5. Filla A, De Michele G, Cavalcanti F, Pianese L, Monticelli A, Campanella G, et al. The relationship between trinucleotide (GAA) repeat length and clinical features in Friedreich ataxia. Am J Hum Genet. 1996;59(3):554-60.
6. Tsou AY, Paulsen EK, Lagedrost SJ, Perlman SL, Mathews KD, Wilmot GR, et al. Mortality in Friedreich ataxia. J Neurol Sci. 2011;307:46-9.
7. Arbour L, Canadian Paediatric Society, Bioethics Committee. Guidelines for genetic testing of healthy children. Paediatr Child Health. 2003;8(1):42-52.
8. Borry P, Evers-Kiebooms G, Cornel MC, Clarke A, Dierickx K, Public, et al. Genetic testing in asymptomatic minors: background considerations towards ESHG Recommendations. Eur J Hum Genet. 2009;17(6):711-9.
9. Borry P, Fryns JP, Schotsmans P, Dierickx K. Carrier testing in minors: a systematic review of guidelines and position papers. Eur J Hum Genet. 2006;14(2):133-8.
10. Botkin JR, Belmont JW, Berg JS, Berkman BE, Bombard Y, Holm IA, et al. Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. Am J Hum Genet. 2015;97(1):6-21.
11. Vears DF, Ayres S, Boyle J, Mansour J, Newson AJ, Education E, et al. Human Genetics Society of Australasia position statement: Predictive and presymptomatic genetic testing in adults and children. Twin Res Hum Genet. 2020;23(3):184-9.
12. Borry P, Stultiens L, Goffin T, Nys H, Dierickx K. Minors and informed consent in carrier testing: a survey of European clinical geneticists. J Med Ethics. 2008;34(5):370-4.
13. Ross LF. Carrier detection in childhood: a need for policy reform. Genome Med. 2010;2(4):25.
14. Borry P, Goffin T, Nys H, Dierickx K. Attitudes regarding predictive genetic testing in minors: a survey of European clinical geneticists. Am J Med Genet C Semin Med Genet. 2008;148C(1):78-83.
15. Mand C, Gillam L, Duncan RE, Delatycki MB. "It was the missing piece": adolescent experiences of predictive genetic testing for adult-onset conditions. Genet Med. 2013;15(8):643-9.
16. Ackerman MJ, Priori SG, Willems S, Berul C, Brugada R, Calkins H, et al. HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA). Heart Rhythm. 2011;8(8):1308-39.
17. Hershberger RE, Lindenfeld J, Mestroni L, Seidman CE, Taylor MR, Towbin JA, et al. Genetic evaluation of cardiomyopathy--a Heart Failure Society of America practice guideline. J Card Fail. 2009;15(2):83-97.
18. Lowe GC, Corben LA, Duncan RE, Yoon G, Delatycki MB. "Both sides of the wheelchair": The views of individuals with, and parents of individuals with Friedreich ataxia regarding pre-symptomatic testing of minors. J Genet Couns. 2015;24(5):732-43.
Disclaimer, intended use and funding
Disclaimer
The Clinical Management Guidelines for Friedreich ataxia (‘Guidelines’) are protected by copyright owned by the authors who contributed to their development or said authors’ assignees.
These Guidelines are systematically developed evidence statements incorporating data from a comprehensive literature review of the most recent studies available (up to the Guidelines submission date) and reviewed according to the Grading of Recommendations, Assessment Development and Evaluations (GRADE) framework © The Grade Working Group.
Guidelines users must seek out the most recent information that might supersede the diagnostic and treatment recommendations contained within these Guidelines and consider local variations in clinical settings, funding and resources that may impact on the implementation of the recommendations set out in these Guidelines.
The authors of these Guidelines disclaim all liability for the accuracy or completeness of the Guidelines, and disclaim all warranties, express or implied to their incorrect use.
Intended Use
These Guidelines are made available as general information only and do not constitute medical advice. These Guidelines are intended to assist qualified healthcare professionals make informed treatment decisions about the care of individuals with Friedreich ataxia. They are not intended as a sole source of guidance in managing issues related to Friedreich ataxia. Rather, they are designed to assist clinicians by providing an evidence-based framework for decision-making.
These Guidelines are not intended to replace clinical judgment and other approaches to diagnosing and managing problems associated with Friedreich ataxia which may be appropriate in specific circumstances. Ultimately, healthcare professionals must make their own treatment decisions on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge and expertise.
Guidelines users must not edit or modify the Guidelines in any way – including removing any branding, acknowledgement, authorship or copyright notice.
Funding
The authors of this document gratefully acknowledge the support of the Friedreich Ataxia Research Alliance (FARA). The views and opinions expressed in the Guidelines are solely those of the authors and do not necessarily reflect the official policy or position of FARA.