Background: Costello syndrome (CS) is a rare autosomal dominant genetic disease, first described in 1971, part of neuro-cardio-facio-cutaneous syndrome (with RAS pathway genes mutations of MAPKinaza-RASopathies), characterized by short stature, delayed mental development, joint hiperlaxity, papillomas, congenital heart defects and increased risk to develop benign or malignant solid tumors.
Case: We present the case of a teenaged girl (15 years 7 months), the second child of an apparently healthy couple, evaluated at the Endocrinological Department in February 2014 for short stature. She presented congenital heart malformations (pulmonary valvular stenosis, interatrial septal defect type ostium secundum operated at 1 year and 3 months, with persistent slight pulmonary valvular stenosis), delayed psychomotor development and physical dysmorphies: curly hair, high forehead, thick eyebrows and lips, down implanted ears, dysplastic nails, multiple palmar skin folds. She was later genetically diagnosed with CS (HRAS gene mutation 11p 15.5). Physical exam confirmed the developmental delay height 142 cm (−3.81 SD), weight 33 kg, BIII PIIIII pubertal development. Bone age was delayed ~11 years. Hormonal balance revealed low basal GH 1.49 ng/ml, with insufficient response to induced hypoglycemia max value 9.95 ng/ml, low IGF1 level 114 ng/ml. GH treatment was decided in order to improve final height.
Conclusions: Patients with CS have high risk of developing malignancies or hypertrophic cardiomyopathy which may be (at least theoretically) favorised by the GH treatment. Actual studies did not show an increase of these complications in children with CS treated with hGH. However, due to the small number of treated children, it is not possible to exclude such an evolution. Given the important growth delay, the slight cardiac defect and the absence of solid tumors, together with the reduced risk and potential high benefits of the GH treatment, we decided to start it, with periodic evaluations.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology