Short Stature in Klinefelter Syndrome From Aggrecan Mutation

Despite tall stature being a characteristic feature of Klinefelter syndrome, occasional cases of short stature have been reported. These cases are often attributed to GH deficiency. This case report details a unique case of a 16-year-old male with Klinefelter syndrome exhibiting proportionate short stature resulting from a heterozygous, likely pathogenic, variant in the ACAN gene c.7141G > A (p.Asp2381Asn). This specific variant, previously identified once in a family with a recessive inheritance pattern is reported here for the first time in an individual with Klinefelter syndrome. This report emphasizes the importance of a thorough evaluation and consideration of genetic testing for an underlying diagnosis in short-statured individuals with Klinefelter syndrome. Timely detection would enable appropriate therapeutic interventions.