Case Report: Clinical phenotypes and recombinant human growth hormone therapeutic exploration for a patient with Takenouchi-Kosaki syndrome harboring the CDC42 p.Arg68Gln variant.

This study reports a pediatric patient harboring the heterozygous CDC42 variant (c. 203G > A, p. Arg68Gln), an ultra-rare variant with limited clinical and genetic data worldwide. She presented with typical Takenouchi-Kosaki syndrome (TKS) manifestations, including severe growth retardation, characteristic craniofacial dysmorphism, persistent macrothrombocytopenia and progressive sensorineural hearing loss. Additional evaluations identified leukopenia, hypogammaglobulinemia and a humoral immunodeficiency. Compound heterozygous GJB2 variants were detected but unlikely to dominate the patient's profound hearing loss. Off-label recombinant human growth hormone (rhGH) therapy was administered for her short stature. During six months of follow-up, favorable catch-up growth was achieved. Literature review was conducted to clarify features of this variant. This study supplements the clinical data of the CDC42 p. Arg68Gln variant, provides preliminary evidence for rhGH intervention, and offers reference information for the clinical management and genetic counseling of patients with TKS.