ESPE Abstracts

Aggrecan, encoded by the ACAN gene, is the main proteoglycan component in the extracellular cartilage matrix. A heterozygous ACAN mutation has been reported as a major cause of idiopathic short stature, it causes an accelerated bone age maturation and premature growth cessation. Recently, the effectiveness of GH treatment for achieving an appropriate adult height has been reported in several cases with ACAN mutations. We report the case of a 3 years and 2 months old boy, with height of 88 cm (SDS -2.5) and weight of 15 kg (0 SDS). He is the only son and he was born to non consanguineous parents. He was born at 39 weeks through cesarean delivery because of mother’s narrowed pelvis and with a birth weight of 3.5 kg. He presented with frontal bossing, a broad chest, a low posterior hairline and a short neck, Tanner stage 1. The mother's and father's heights were 143 cm (-3 SDS) and 173 cm (-0.5 SDS) respectively. The patient's bone age was 2 years more advanced than his chronological age using the standard Greulich-Pyle method. Pelvic and knees x-ray imaging did reveal a bilateral ostechondral defects, enlargement of the proximal tibial and distal femoral metaphyses, irregular femoral epiphysis and patellar contours. The patient's mother had short stature, and early-onset lumbar disc herniation, patellofemoral dysplasia, degenerative chondral involvement of the patella, and degenerative bone remodeling of the trochlea, were all confirmed with MRI in her 23 age. ACAN mutation was suspected. Exome sequencing of a targeted growth panel (ECCTV3 Short Stature Comprhensive Panel: 286 genes) revealed 2 new heterozygous ACAN vatriants: c.7127G>A (p.Arg2376His) and c.386G>A (p.Gly129Glu) in the boy. No endocrine abnormalities were detected except a probable partial GHD (GH peac in Glucagon stimulation test realised at 3 years and 7 months age: 6.79 ng/ml with normal pituitary MRI). rhGH treatement had been started at a dose of 1mg/m2 since 8 months. His height velocity ranged from 6 to 7.5 cm/year. Short stature is generally associated with a delayed bone age, and this case suggests that ACAN mutations may be the most likely etiology of short stature associated with an advanced bone age and should warrant early treatment. The response of GH treatment should be further examined with long-term outcomes.