Multidisciplinary Approach to Managing Hypotonia and Developmental Delays Due to a Novel GTPBP3 Mutation

Introduction: Hypotonia in early life is often challenging to diagnose due to its diverse etiologies, with genetic disorders accounting for about one-third of cases. A precise diagnosis using a comprehensive, multidisciplinary approach is crucial for determining prognosis, guiding treatment, and providing genetic counseling. Case Presentation: We report the first case in Taiwan involving compound heterozygous mutations in the GTPBP3 gene. A 13-month-old girl presented with developmental delays and hypotonia despite normal prenatal screenings and a year of rehabilitation therapy. Next-generation sequencing revealed two novel mutations: c.785A>C (p.Gln262Pro), a missense mutation in Exon 5, and c.1175_1181dup (p.Ser395GlufsTer4), a frameshift duplication in Exon 7. Both variants were classified as likely pathogenic based on the American College of Medical Genetics and Genomics (ACMG) guidelines. Sanger sequencing confirmed a trans inheritance pattern, with the father carrying the c.785A>C mutation and the mother carrying the c.1175_1181dup mutation. The asymptomatic sibling carried only the c.785A>C variant, supporting an autosomal recessive model. The patient received individualized care from a multidisciplinary team, including a pediatric physiatrist, physical, occupational, and speech therapists, along with support from a social worker. By 46 months, the patient demonstrated significant progress in both motor and language skills. Conclusion: This case underscores the importance of early genetic testing in infants with unexplained hypotonia. Identifying compound heterozygous GTPBP3 mutations allowed for precise diagnosis and guided effective, personalized interventions, highlighting the value of integrating genetic evaluation into clinical management for rare developmental disorders.