Concurrent mutations in RNU4ATAC, PLEC, and CD96 in a child with severe short stature and skeletal dysplasia: a case report.

Background: Polygenic mutations play a significant role in the etiology of various growth-related disorders and bone deformities, influencing multiple physiological processes. Understanding the impact of polygenic mutations is crucial for the diagnosis, genetic counseling, and management of these complex conditions.

Case presentation: A boy first evaluated at 9 years and 10 months for short stature was diagnosed with compound heterozygous mutations in PLEC, CD96, and RNU4ATAC genes, with comorbid congenital multiple epiphyseal dysplasia and growth hormone deficiency. These mutations collectively contributed to severe short stature, skeletal deformities, and delayed neurodevelopment. Orthopedic surgeries were performed at 9 years and 10 months (first intervention), 11 years and 6 months (second intervention), and 12 years and 9 months (third intervention), while growth hormone therapy (GHT) was initiated at 11 years and 10 months. Over 25 months of GHT, his height increased by 18 cm, bone age advanced by five years, and gait improved. Final clinical evaluation at 13 years and 11 months confirmed sustained improvements in height (137 cm) and motor function.

Conclusion: This case involves a child with short stature caused by rare mutations of PLEC, CD96, and RNU4ATAC. This is the first case report documenting the concurrent presence of all three rare mutations. Orthopedic surgery and GHT were employed to improve the patient's development and quality of life. We propose that early identification of high-risk factors, genetic screening, and comprehensive treatment can enhance therapeutic effectiveness and improve the patient's quality of life.