Clinical and Genetic Characterization of a Cohort of Small-for-Gestational-Age Patients: Cost-Effectiveness of Whole-Exome Sequencing and Effectiveness of Treatment with GH.

Background/Objectives: Develop a clinical and genetic characterization, in a group of small-for-gestational-age (SGA) patients who did not experience catch-up growth Methods: In an ambispective cohort study with (SGA) patients. These patients received one treatment with growth hormone (GH) over 14 years. This study analyzes their response to treatment and conducts a genetic analysis in order to identify cases with specific phenotypic and auxological characteristics, defined as presenting two or more dysmorphic traits and/or a stature below -3 SDS (standard deviation score). Whole-exome sequencing (WES) was performed on selected patients. Results: Forty-four SGA patients were examined, with an average age of 6.4 (2.49) years and an initial size of -3.3 SDS. The pubertal growth was 24.1 (5.2) cm in boys and 14.7 (4.3) cm in girls. WES in 11 SGA patients revealed conclusive genetic variants in eight, including two pathogenic ACAN variants, one 15q26.2-q26.3 deletion, and four variants of uncertain significance in other genes. Conclusions: Treatment with GH in SGA patients was shown to be effective, with a similar response in the group with positive genetic results and in the group who did not undergo a genetic study. Genetic testing based on auxological and clinical criteria proved highly cost-effective.

Factors influencing height gain in children born small for gestational age treated with recombinant growth hormone: what extent is puberty involved?

Objective: The objective was to analyze the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) without catch-up growth treated before the onset of puberty, with follow-up until adult height. The influence of demographic and auxological factors on the final response evaluated as adult height and height gain was assessed. Patients and methods: A prospective longitudinal observational study performed in a tertiary hospital, involving SGA patients, who started treatment with rhGH between October 2003 and April 2015. Potential response predictors were evaluated by multiple regression analysis and receiver operating characteristic curves. Results: Of the initial 96 patients included, 61 patients (28 boys and 33 girls) reached adult height. Adult height gain in standard deviation (SDS) was 0.99 (0.8) and 1.49 (0.94), respectively (p < 0.05). An adult height greater than -2 SDS was reached in 75% of the girls but only in 53% of the boys. The pubertal height gain was 22.6 (5.8) cm in boys and 18.8 (4.5) cm in girls. The multiple regression model obtained for total height gain explained 42% of the variability in this variable including sex, height gain during the first year, and the difference from target height at the start of treatment. A first-year height gain of 0.69 SDS was the optimal point for assessing a final height gain greater than 1.5 SDS with a specificity of 70% and a sensitivity of 71%. Conclusion: Most SGA patients achieve normalization of height above -2 SD, the percentage being higher in girls. According to our predictive model, height gain in the first year is the most important variable for predicting good response to treatment. During puberty, there is a loss of height SDS, probably due to a lower total pubertal gain with respect to the reference population, which is more marked in boys.