When to order genetic tests in pediatric endocrinology: Indications, modalities, interpretation, and practical pitfalls

Genetic testing plays an important role in pediatric endocrine disorders by establishing an etiological diagnosis, guiding targeted therapy, refining prognosis, and enabling appropriate genetic counseling. Test selection should be driven by clinical phenotype, biochemical findings, and the suspected genetic mechanism. Clinically available genetic testing methods can be broadly classified into three major categories: classical cytogenetics, molecular cytogenetic techniques, and sequencing-based approaches. Selecting the most appropriate test requires not only an understanding of the genetic basis of a disorder but also careful consideration of each method’s strengths and limitations. Herein, we first provide the readers with an overview of the commonly available genetic tests, with special reference to their application in diagnosing pediatric endocrine disorders. The case scenarios in the next section shall exemplify the above. Finally, in the era of high-throughput, massively parallel next-generation sequencing, it has become imperative to understand how to handle variants of uncertain significance, for which a guide is provided at the end of the review.