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. 2021 Dec;100(6):752-757.
doi: 10.1111/cge.14057. Epub 2021 Sep 16.

Diagnostic yield of genetic testing in 324 infants with hypotonia

Sonal Sharma  1   2 , Elena Repnikova  3   4 , Janelle R Noel-MacDonnell  4   5 , Jean-Baptiste LePichon  1   4
Affiliations

Diagnostic yield of genetic testing in 324 infants with hypotonia

Sonal Sharma et al. Clin Genet. 2021 Dec.

Abstract

This retrospective cohort study was designed to determine the yield of genetic tests in hypotonic infants and develop a diagnostic algorithm. Out of 496 patients identified by International Classification of Diseases (ICD) 9/10 coding, 324 patients met the inclusion criteria. Diagnostic yields were 32% for karyotype, 19% for microarray, 30% for targeted genetic tests, 38% for gene panels, and 31% for exome sequencing. In addition, we considered the diagnostic contribution of ancillary tests, including neuroimaging, metabolic tests, and so forth. The combination of microarray and exome sequencing gave the highest diagnostic yield. None of the other tests added significant value in arriving at a diagnosis. Based on these results we propose that the vast majority of infants with congenital hypotonia should start with a microarray and proceed with exome sequencing, with the notable exception of infants with clearly syndromic features in whom karyotyping or targeted testing may be more appropriate.

Keywords: genetic testing; hypotonia; syndrome; whole exome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of diagnostic yield of genetic testing in study population
FIGURE 2
FIGURE 2
Infants with hypotonia require a step‐wise approach toward diagnosis. In the absence of clinical features associated with a specific genetic disease, the highest diagnostic yield can be achieved by microarray with reflex to whole exome sequencing
See this image and copyright information in PMC

References

    1. Sparks SE. Neonatal hypotonia. Clin Perinatol. 2015;42(2):363‐371. - PubMed
    1. Le Pichon JB, Shapiro S. Neonatal Hypotonia. In: Stevenson DK, Cohen RS, Sunshine P, eds. Neonatology: Clinical Practice and Procedures. McGraw‐Hill Education; 2015:211‐235.
    1. Bodensteiner JB. The evaluation of the hypotonic infant. Semin Pediatr Neurol. 2008;15:10‐20. - PubMed
    1. Lisi EC, Cohn RD. Genetic evaluation of the pediatric patient with hypotonia: perspective from a hypotonia specialty clinic and review of the literature. Dev Med Child Neurol. 2011;53(7):586‐599. - PubMed
    1. Laugel V, Cossée M, Matis J, et al. Diagnostic approach to neonatal hypotonia: retrospective study on 144 neonates. Eur J Pediatr. 2008;167(5):517‐523. - PubMed

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