Genomic testing using next-generation sequencing may be advantageous in diagnosing patients born small for gestational age (SGA) with persistent short stature, according to study findings published in The Journal of Clinical Endocrinology & Metabolism.

Children born SGA who continue to have short stature during childhood have a high probability of continuing to be below normal range into adulthood. With new genomic technologies, a genetic diagnosis can be made in many children with short stature of unknown cause, although no studies to date have focused on children born SGA with isolated short stature. In the current study, researchers evaluated the use whole exome sequencing and/or targeted panel sequencing in a cohort of 55 nonsyndromic children born SGA with persistent short stature. Patients with several dysmorphic features, major malformations, or other characteristics in addition to short stature were excluded.

The researchers reported heterozygous pathogenic or likely pathogenic genetic variants in 8 participants, with all of the variants identified in genes already implicated in growth disorders. Of these genes, 4 were associated with growth plate development: Indian hedgehog (IHH; n = 2), natriuretic peptide receptor 2 (NPR2; n = 2), short stature homeobox (SHOX; n = 1), and aggrecan (ACAN; n = 1). Two genes, protein-tyrosine phosphatase nonreceptor-type 11 (PTPN11; n = 1) and neurofibromin 1 (NF1; n = 1), were involved in the RAS-MAPK pathway. There were no clinical findings in any of the patients that would allow for a diagnosis.

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“Our results should encourage prospective studies that include patient well-being and economic cost-benefit evaluations to guide future recommendations for genetic testing using a genomic approach for children born SGA,” wrote the researchers.

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Freire BL, Homma TK, Funari MFA, et al. Multigene sequencing analysis of children born small for gestational age with isolated short stature [published online January 2, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2018-01971