Ethical implications of early genetic diagnosis in an infant with Lesch–Nyhan syndrome

Pathogenic variants in HPRT1 lead to deficiency in hypoxanthine‐guanine phosphoribosyltransferase and are responsible for a spectrum of disorders. The severe phenotype is termed Lesch–Nyhan syndrome (LNS) and is inherited in an X‐linked recessive manner. Most individuals with LNS have profound intel...

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Bibliographic Details
Published inJournal of genetic counseling Vol. 31; no. 6; pp. 1434 - 1437
Main Authors Zhang, Tian, Briere, Julie M., Leeman, Kristen T., Wojcik, Monica H., Agrawal, Pankaj B.
Format Journal Article
LanguageEnglish
Published United States Blackwell Publishing Ltd 01.12.2022
Subjects
Decision making
Diagnosis
Diagnostic tests
Early Diagnosis
Ethics
exome sequencing
Exons
Gene deletion
genetic diagnosis
Genetic screening
Genetic testing
HPRT1
Humans
Hypoxanthine
Hypoxanthine Phosphoribosyltransferase - genetics
Infants
Lesch-Nyhan Syndrome - diagnosis
Lesch-Nyhan Syndrome - genetics
Lesch–Nyhan syndrome
Male
Medical diagnosis
neonatal
Newborn babies
pediatrics
Phenotype
Phenotypes
Phosphoribosyltransferase
Physical disabilities
Variants
Lesch-Nyhan syndrome
exome sequencing
pediatrics
neonatal
genetic diagnosis
HPRT1
ethics
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Summary:Pathogenic variants in HPRT1 lead to deficiency in hypoxanthine‐guanine phosphoribosyltransferase and are responsible for a spectrum of disorders. The severe phenotype is termed Lesch–Nyhan syndrome (LNS) and is inherited in an X‐linked recessive manner. Most individuals with LNS have profound intellectual and physical disabilities throughout life including self‐mutilating behaviors. Here, we present the case of a male infant who was diagnosed with LNS at 3 weeks of age via rapid exome sequencing (ES), which revealed a hemizygous maternally inherited deletion of at least 1.3 Mb of Xq26.3, including exons 2 to 9 of HPRT1. We discuss the critical time points leading to this diagnosis while highlighting his parents' values that guided the decision‐making. Genetic testing provided an early diagnosis for this infant that led to important considerations regarding goals of care in addition to raising new ethical concerns. This highlights the important role that early and rapid diagnostic genetic testing can play in helping families make difficult decisions. Additionally, this case highlights the complexity of discussing rare genetic diagnoses with families and facilitating critical discussions to empower the family toward making an informed decision.
Bibliography:Funding information
Tian Zhang and Julie M. Briere should be considered joint first authors.
Monica H. Wojcik and Pankaj B. Agrawal should be considered joint senior authors.
MHW is supported by the National Institutes of Health under grant number K23HD102589
Revising draft: TZ, JMB, MHW, PBA, KTL
Conception or design of the work: PBA
Acquisition, analysis, or interpretation of data: TZ, JMB, MHW, PBA
Tian Zhang and Julie M. Briere should be considered joint first authors. Monica H. Wojcik and Pankaj B. Agrawal should be considered joint senior authors.
Author Contributions
Drafting the work: TZ, JMB, KTL
All of the authors gave final approval of this version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
ISSN:1059-7700
1573-3599
DOI:10.1002/jgc4.1616