THU169 Role Of Growth Hormone (GH) Therapy In Short Children With Skeletal Dysplasias And Pathogenic Variants In The COL2A1 Gene

Abstract Disclosure: L.D. Cellin: None. K.G. Guimaraes: None. N.L. Menezes De Andrade: None. G.A. Vasques: None. E.D. Goiano: None. M. Akkari: None. C. Santili: None. A.A. Jorge: None. A.C. Malaquias: None. Introduction: COL2A1 is the primary collagen synthesized by chondrocytes and plays a critical structural role in regulating cell growth, differentiation, and migration. Mutations in the COL2A1 gene may cause heterogeneous phenotypes ranging from skeletal dysplasia to nonsyndromic short stature. Clinical characteristics in COL2A1-related disorders are abnormalities in the ocular, skeletal, oro-facial, and audiological systems. Unfortunately, data were scarce about GH treatment in short children with pathogenic variants in COL2A1.Objective: To evaluate recombinant growth hormone (GH) treatment in short children carrying mutations in the COL2A1 gene. Methods: Retrospectively, we selected 8 prepubertal patients with short stature and pathogenic variants in the COL2A1 gene who were treated with GH (mean dose of 45.8 ± 7.9 µg/kg/d at the start). The primary outcomes were changes in height SDS and growth velocity in the 1st year and at the end of treatment. Results: Five patients were male; 3 were disproportionate, and 5 showed skeletal dysplasia signs. Two had familial short stature. At the start of the treatment, the mean calendar age was 8.1 ± 3.9 yr, and bone age was 6.9 ± 4.2 yr. The mean height SDS was -4.0 ± 0.9 for the CDC reference. In the 1st year of therapy, the growth velocity (GV) increased from baseline values of 5.2 ± 1.9 cm/yr to 7.4 ± 1.4cm/yr, an increment of 2.2 ± 2.2cm (p=0.02). GV SDS increased from -1.2 ± 1.5 to 1.2 ± 1.8 in the whole cohort during the 1st year of treatment (p=0.02). Height SDS showed a modest improvement after one year of therapy (from -4.0 ± 0.9 to -3.5 ± 0.9; p=0.005). To improve adult height, we treated two patients with GnRH analogs associated with GH. After a mean duration of therapy of 5.5 ± 2.5 years, 5 patients ended the treatment with rhGH (one prematurely stopped therapy due to poor growth response). No increment was observed in height SDS at the end of treatment (from -3.8 ± 0.9 to -3.4 ± 1.3; p=0.2). Four patients achieved adult height after 6.4 ± 1.7 years of therapy (height SDS ranging from -3.4 ± 0.4 to -2.9 ± 0.8; p=0.08). The mean gain in adult height SDS was 0.5 ± 0.4 (ranging from zero to 0,97). Conclusions: Our patients with COL2A1-associated disorders showed no response to GH therapy to improve adult height as a group. However, we need more studies to determine which patient will benefit from this treatment once there is considerable phenotype heterogeneity. GnRH analogs may help to improve adult height in association with GH. Also, alternative therapies might be evaluated to treat short children with these disorders. Presentation: Thursday, June 15, 2023