Study Highlights Importance of Genetic Sequencing to Diagnosis of Growth Disorders
Published on February 19, 2024
In a groundbreaking study, researchers based in Brazil have shed light on the critical role of genetic sequencing in diagnosing growth disorders. Their findings, published in the Journal of Pediatrics, underscore the value of this cutting-edge technology in unraveling complex medical cases.
The Case of a Nine-Year-Old Boy
The study centers around a nine-year-old boy who was admitted to the hospital with a constellation of symptoms. His condition presented a diagnostic challenge due to overlapping features, including:
Short stature
Thin tooth enamel (dental enamel hypoplasia)
Moderate mental deficiency
Speech delay
Asthma
Mildly altered blood sugar
History of recurring infections in infancy
Given the complexity of the case, the research team turned to exome sequencing. This advanced technique focuses on analyzing only the protein-coding portion of the genome. Through this method, they identified genetic mutations in two specific genes: GCK and BCL11B. The final diagnosis? Monogenic diabetes and T-cell abnormality syndrome—both rare diseases.
Reducing the Diagnostic Odyssey
Dr. Alexander Augusto de Lima Jorge, the last author of the article, emphasized the significance of exome sequencing. He stated, "Exome sequencing is a very useful technology to reduce what we call the diagnostic odyssey—the long journey patients with rare or complex conditions have to undergo until they receive a proper diagnosis." Over the past decade, the cost of this test has significantly decreased, making it more accessible to patients.
The study involved 115 patients with syndromic growth disorders of unknown origin. Remarkably, 63 patients received a definitive diagnosis based on genetic analysis. Notably, 9.5% of these cases had multiple diagnoses, surpassing previous studies. Lima Jorge highlighted the importance of using broad genetic tests, such as whole exome or whole genome sequencing, to uncover rare diseases that contribute to complex clinical presentations.
Genetic Factors and Growth
While short stature or tall stature alone is not a diagnosis, it remains a crucial clinical finding. Dr. Lima Jorge explained, "In healthy children with short or tall stature as the only manifestation, there will probably be a polygenic basis [where stature is influenced by several genetic variants]. However, in syndromic growth disorders—where short or tall stature coexists with other features like mental deficiency, deafness, autism spectrum disorder, or malformation—an alteration in one or more genes is more likely to explain the complex phenotype."
With an estimated 5% to 10% of the world's population affected by rare diseases, advancements in genetic sequencing hold immense promise. As we continue to decode the intricacies of our DNA, we move closer to personalized and precise medicine.