AI Article Synopsis

  • Short stature (SS) refers to children who are significantly shorter than their peers and can be caused by various medical conditions, including genetic factors.
  • Researchers used next-generation sequencing (NGS) to investigate the genetic causes of SS in 125 Italian children with unknown origins of their condition.
  • The study found 43 potentially harmful genetic variants in 38 children, with some diagnosed with specific syndromic conditions, highlighting the importance of genetic analysis for accurate diagnosis and personalized treatment.

Article Abstract

Background: Short stature (SS) is defined as height more than 2 standard deviations below the mean for age and sex. Hypothyroidism, celiac disease, growth hormone deficiency, hormonal abnormalities, and genetic conditions are among its causes. A wide range of conditions often due to largely unknown genetic variants can elude conventional diagnostic workup.

Aim: We used next-generation sequencing (NGS) to better understand the etiology of SS in a cohort of Italian children.

Patients And Methods: The study sample was 125 children with SS of unknown origin referred to our Institute between 2015 and 2021. All had undergone complete auxological and hormonal investigations to exclude common causes of SS. Genetic analysis was performed using a NGS panel of 104 genes. Clinical data were reviewed to clarify the pathogenicity of the variants detected.

Results: In this cohort, 43 potentially causing variants were identified in 38 children. A syndromic genetic condition was diagnosed in 7: Noonan syndrome in 3, Leri-Weill syndrome in 3, and hypochondroplasia in 1. Moreover, 8 benign variants and other 37 like benign variants were found. In 88 children, 179 variants of uncertain significance (VUS) were identified. No variant was found in 16 children.

Conclusion: Genetic analysis is a useful tool in the diagnostic workup of patients with SS, in adapting management and treatment, and in identifying syndromes with mild atypical clinical features. The role of VUS should not be underestimated, particularly when multiple VUS with possible mutual worsening effects are present in the same child.

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Source
http://dx.doi.org/10.1007/s40618-023-02243-9DOI Listing

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