No abstract

We observed an improvement in bone and muscle parameters after cholecalciferol substitution in pediatric patients with IBD. Therefore, vitamin D substitution can be considered in such patients.

Context The C-type natriuretic peptide receptor encoded by the NPR2 gene is a paracrine regulator of the growth plate; heterozygous NPR2 variants cause short stature with possible presence of different signs of bone dysplasia. To date, the effect of growth hormone (GH) treatment has been described in a few individuals with NPR2 gene variants with inconsistent results. Objectives To identify NPR2 gene variants among children with familial short stature (FSS) and to describe their phenotype, including GH treatment response. Design, Settings and Patients Out of 747 patients with short stature treated with GH in a single center, 87 with FSS met the inclusion criteria (pretreatment height ≤ –2 standard deviation in both the patient and the shorter parent, unknown genetic etiology). Next-generation sequencing methods were performed to search for NPR2 gene variants. The results were evaluated using the American College of Medical Genetics and Genomics guidelines. The GH treatment response (growth velocity improvement and height standard deviation score development over the first 5 years of treatment) was evaluated. Results In 5/87 children (5.7%), a (likely) pathogenic variant in the NPR2 gene was identified (p.Ile558Thr [in 2], p.Arg205*, p.Arg557His, p.Ser603Thr). Two children had disproportionate short-limbed short stature, 1 a dysplastic 5th finger phalanx. The growth velocity in the first year of GH treatment accelerated by 3.6 to 4.2 cm/year; the height improved by 1.2 to 1.8 SD over 5 years of treatment. Conclusions NPR2 gene variants cause FSS in a significant proportion of children. Their GH treatment response is promising. Studies including final height data are necessary to assess the long-term efficacy of this therapy.

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.