ESPE Abstracts

Background: The current era is marked by significant advancements in genomic medicine, characterized by innovative technologies in both cytogenetics and molecular methods. As these technologies evolve, costs decrease, making genetic testing more accessible and feasible. This trend is particularly evident in the field of genetic endocrine disorders. Presently, chromosomal microarrays and next generation sequencing are the predominant methods utilized. In the near future, whole genome sequencing, especially utilizing long-read technology, is expected to become a standard practice.

Objective: Our study aims to evaluate the necessity of karyotype testing in endocrine disorders, considering its advantages and disadvantages, and identifying scenarios in which karyotyping provides critical diagnostic information that advanced genomic techniques may miss.

Methods: We conducted an analysis of 353 pediatric patients who were referred to the endo-genetic clinic between January 2018 and May 2024. Data were collected retrospectively, focusing on the reason for referral, recommended genetic tests, and final diagnosis.

Results: Out of the 353 pediatric patients, 35 (~10%) were referred for karyotype testing. The most common reasons for referral were short stature, differences in sex development (DSD), and primary ovarian insufficiency. Of these patients, 23 (66%) completed the karyotype test. Abnormal karyotypes were detected in 14 patients (60%), including cases of classic Turner and Klinefelter syndrome, as well as more complex genotypes such as Turner syndrome with a ring chromosome, a male patient with an isodicentric Y chromosome, chromosomal translocations, and rare mosaicisms (e.g., a male patient with a 45X/46X, Ydelq karyotype and a female patient with 47XYY/45X mosaicism).

Conclusions: Chromosomal abnormalities are a common finding, especially in endocrine disorders, and are particularly prevalent in cases of short stature and differences in sex development (DSD). Hence, karyotype testing remains a valuable and cost-effective diagnostic tool for pediatric endocrine disorders. Despite the advancements in genomic methods, karyotyping can sometimes surpass more advanced techniques. It is particularly essential for diagnosing cases involving isodicentric chromosomes, ring chromosomes, complex mosaicism, and translocations, which are undetectable by most cytogenetic methods such as chromosomal microarray analysis or molecular techniques. However, the future holds significant change as long-read whole genome sequencing is expected to become a standard diagnostic tool. This technology will enable the diagnosis of sequence variants, structural variants, copy number variations, tandem repeats, and phasing, all within a single test.