Follow-Up Study of Growth Hormone Therapy in Children with Kabuki Syndrome: Two-Year Treatment Results

Abstract

Introduction: Kabuki syndrome (KS) is a genetic disorder with characteristic facial dysmorphisms, short stature, hypertension, and obesity later in life. The aim of this study was to evaluate catch-up growth and cardiovascular markers before and during growth hormone (rhGH) treatment in KS children. Methods: This prospective study included 18 children whose KS was genetically established. Each KS subject received rhGH for a period of 2 years. Several measurements were performed before and during treatment: anthropometry, glucose metabolism, lipid profile, markers for endothelial function, and low-grade inflammation. Results: This study found an increase in delta height standard deviation score (SDS) for the whole group of 1.1 SDS after 2 years of rhGH treatment. Baseline metabolic profiles showed no cardiometabolic abnormalities in these children. Although 4 out of 18 children were obese, there were no signs of the metabolic syndrome. During rhGH treatment, serum lowdensity lipoprotein cholesterol concentrations decreased significantly (2.16-1.91 mmol/L, p = 0.04). Apolipoprotein B100 concentrations also showed a reduction after 24 months of treatment, but the other lipid and (apo)lipoprotein parameters did not change. While other endothelial function markers were stable, only vascular cell-adhesion molecule-1 concentrations increased (1,084-1,161 pg/mL, p < 0.01) during rhGH therapy. Furthermore, BMI and waist circumference improved during treatment. There were no signs of hypertension. Conclusions: At baseline and during rhGH therapy, there were no signs of the metabolic syndrome. This is the first study demonstrating that rhGH treatment in KS children is a safe and effective therapy and that it positively influences linear height without exerting adverse effects on a wide array of cardiovascular risk markers.

Growth, body composition, and endocrine‐metabolic profiles of individuals with Kleefstra syndrome provide directions for clinical management and translational studies

“…Triglycerides were significantly increased in KLFS compared to sex‐ and age‐matched controls, while there were no differences in cholesterol, HDL, and LDL. Triglycerides remain significantly increased compared to an age‐ and BMI‐matched Kabuki syndrome cohort (van Montfort et al, 2021) (Supplementary File 5). With the inclusion of individuals having a BMI Z ‐score within the range of −1 to 1, the mean triglyceride levels in the KLFS group are 1.22 ± 0.65 mmol/L, whereas they are 0.61 ± 0.19 mmol/L in the Kabuki syndrome ( p < 0.03).…”

From Genotype to Phenotype—A Review of Kabuki Syndrome

“…There is limited research evaluating the impact of recombinant human growth hormone (rh-GH) therapy in children with KS. Several small studies have shown promising results, demonstrating statistically significant increases in linear growth following at least one year of rh-GH therapy, without negatively impacting cardiovascular health [ 123 , 124 , 125 ]. Without growth hormone therapy, adult height may fall anywhere from −5.57 SD and −1.08 SD below the mean for healthy controls, with females more severely affected than males [ 126 ].…”

Diabetes mellitus and insulin resistance associated with Kabuki syndrome—A case report and literature review

“…Growth hormone (GH) deficiency is one of the most common endocrine complications in KS patients (but not seen in the present case), and recombinant human GH had been recently found to be beneficial on linear height without adverse effects. 16 However, the association between GH administration and worsening insulin resistance should be cautioned in high‐risk patients as shown in a recent Japanese case report. 8 …”