SHOX haploinsufficiency (SHOX-D) is a cause of disharmonic short stature and a possible genetic cause of idiopathic short stature also in familial cases. We describe clinical, hormonal and genetic characteristics of patients with SHOX-D haploinsufficiency, followed and treated in the period 20142017, in a single Italian centre. The Rappold score was used to screen short children, to select those who needed a genetic analysis of SHOX gene by MLPA and sequencing. We selected 6 patients (5 females; 1 male; age: 1.211 years), with documented mutations of the SHOX gene or of the promoter. One patient was already treated with low doses of GH for GHD, documented by 2 tests. One patient had type 1 DM; GH treatment in a first phase worsened glycaemic control, otherwise corrected by an increased insulin dose. One patient was first diagnosed in another centre as GHD and was treated with substitutive doses of GH. She came to our centre for the follow up and we noted the disharmonic short stature. The genetic study confirmed SHOX-D. Hence, she progressively increased GH dose, for the low improvement in growth. Two patients born SGA: one for length; the other for weight. One patient was studied for the SHOX-D relieved in the short sister and in the mother. Rappold score was >7 in 50% of the patients. Younger children did not show radiologic signs of SHOX-D, well documented in 2 with Madelung deformity, radiographic lucency of the distal radius on the ulnar side, carpal pyramidalization. The male patient had a duplication of the regulatory region of the gene; 3 patients had a deletion of the regulatory region of SHOX gene; 2 patients had a punctiform mutation of SHOX gene. All the patients were treated with GH, at different dosages in relation to the first diagnosis and to the drug response in growth velocity, and significantly improved height velocity and the best results were obtained in patients who started earlier GH.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology