A rare cause of short stature - A case report

Abstract

Silver-Russell Syndrome is a rare and clinically diverse condition characterized by growth restriction and various dysmorphias. Genetic testing confirms the diagnosis in up to 60% of cases, commonly revealing hypomethylation of the imprinted control region 1 (ICR1) on chromosome 11p15. This case report presents a five-year-old girl with SRS due to a de novo pathogenic variant (c.100G>A p. (Gly34Ser)) in the Insulin Growth Factor-2 (IGF2) gene. Despite normal thyroid function under levothyroxine, her height consistently fell below the third percentile. Clinical exome sequencing identified the IGF2 variant on the paternal chromosome, establishing the Silver-Russell Syndrome diagnosis. The child is undergoing follow-up with levothyroxine and growth hormone treatment. This case underscores the importance of genetic testing in diagnosing and managing short stature conditions, particularly in revealing rare etiologies like IGF2 variants. The Netchine-Harbison Clinical Scoring System aids in clinical diagnosis, while an interdisciplinary approach tailored to comorbidities is crucial for effective management. The prognosis for SRS is generally favorable, emphasizing the significance of genetic alterations in short stature for clinical follow-up and family genetic counseling.