Abstrakt
CONTEXT: :Collagens are the most abundant proteins in the human body. In a growth plate, collagen types II, IX, X and XI are present.
Defects in collagen genes cause heterogeneous syndromic disorders frequently associated with short stature. Less is known about oligosymptomatic collagenopathies.
OBJECTIVES: :To evaluate the frequency of collagenopathies in familial short stature (FSS) children and to describe their phenotype, including growth hormone (GH) treatment response. DESIGN, SETTINGS AND PATIENTS: Eighty-seven FSS children (pretreatment height <=-2 SD in both patient/their shorter parent) treated with GH were included in the study.
Next-generation sequencing was performed to search for variants in COL2A1, COL9A1, COL9A2, COL9A3, COL10A1, COL11A1 and COL11A2 genes. The results were evaluated using ACMG guidelines.
The GH treatment response of affected children was retrospectively evaluated. RESULTS: A likely pathogenic variant in the collagen gene was found in 10/87 (11.5%) children.
Detailed examination described mild asymmetry with shorter limbs and mild bone dysplasia signs in 2/10 and 4/10 affected children, respectively. Their growth velocity improved from a median of 5.3 cm/year to 8.7 cm/year after one year of treatment.
Their height improved from a median of -3.1 SD to -2.6 SD and to -2.2 SD after one and three years of therapy, respectively. The final height reached by 4/10 children differed by -0.67 to +1.0 SD and -0.45 to +0.5 SD compared to their pretreatment height and their affected untreated parent's height, respectively.
CONCLUSION: Oligosymptomatic collagenopathies are a frequent cause of FSS. The short-term response to GH treatment is promising.