Growth outcomes following recombinant human growth hormone therapy in Zhu-Tokita-Takenouchi-Kim syndrome.

Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare multisystem developmental disorder caused by heterozygous pathogenic variants in SON. Short stature is common, but data on endocrine function and response to recombinant human growth hormone (rhGH) are limited. We describe a female child with genetically confirmed ZTTK syndrome presenting with profound proportionate short stature, hypotonia, and developmental delay. Insulin-like growth factor 1 (IGF-1) of 91 ng/mL (Systeme international [SI]: 11.9 nmol/L; reference range, 33.6-170.5 ng/mL [SI: 4.4-22.3 nmol/L]) was normal, and peak growth hormone (GH) concentration on arginine stimulation testing was 7.2 ng/mL (SI: 21.6 mIU/L], above the UK diagnostic cutoff for GH deficiency (<6.7 ng/mL [SI: <20.1 mIU/L]). Given severely impaired linear growth and declining height velocity, a monitored trial of rhGH was initiated. Treatment with rhGH (0.035 mg/kg/day) resulted in >50% increase in height velocity from baseline (4.3-7.2 cm/year), suggesting a good response to rhGH, with sustained improvement over 2 years (height standard deviation score -4.16 to -3.40). Insulin-like growth factor 1, thyroid function, glucose, and glycated hemoglobin A1c remained normal. No adverse effects were observed. This case demonstrates a clinically significant growth response to rhGH in ZTTK syndrome despite absence of biochemical GH deficiency, supporting a supervised 12-month therapeutic trial.