ESPE Abstracts

Short stature is a frequent disorder in the pediatric population caused by multiple possible reasons. One of them it can be the mutation of the ACAN gene, with an autosomal dominant transmission, which also correlates with accelerated bone maturation and early osteoarthritis up to bone dysplasia. A 10.8-year-old patient came to our observation for poor statural growth (125.8 cm, -2.6 SDS) with a parental target of 150.4 cm +/- 8 cm (-2 SDS), on Triptorelin braking therapy, since she was ten years old, for central precocious puberty (CPP) diagnosed by another center. She was born full-term from regular pregnancy with eutocic delivery (birth weight 3.3 kg, length 46 cm, head circumference 36 cm; AGA); psychomotor development was normal and statural growth was always on the lower centiles for sex and age. Our patient had positive family history for short stature (maternal lineage and younger sister). At the first visit the objective examination showed B1 PH 2 of pubertal stages (Tanner Scale), vitiligo, plantar flatness, mild frontal bumps, alonate eyes, flat nasal filter, stubby fingers and toes, thickened articulation between I and II metacarpals and macrocephaly. In subsequent follow-up bone pain occurred (especially at knee level) and it was subsequently diagnosed as osteoarthritis. Several investigations were performed, among which serial first-level blood checks with assessment of IGF-1 (in normal range), Arginine stimulation test for GH (negative), hand x-ray (bone age and chronological age matched); MRI of the hypothalamic-pituitary axis (normal); karyotype analysis (46 XX), SHOX gene analysis (no alterations), genetic analysis for Noonan syndrome (negative) and Ehlers-Danlos syndromes (negative; but it was positive in her dad and in her sister), NGS panel for short stature was positive for variant in exon 12 of ACAN gene (pathogenic feature). Biosynthetic growth hormone therapy was administered, after Regional Commission approval, from when she was eleven to when she was sixteen, obtaining a constant good growth velocity. She continued therapy until reaching her final stature of 146.6 cm (1°; SDS -2.5 with a statural gain of -0.23 SDS from the start of GH treatment and 0.35 SDS from the interruption of braking therapy) with complete bone maturation, confirmed by hand x-ray. Bilateral osteoarthritis dissecans was treated with surgery and it is currently in orthopedic follow-up.