ESPE Abstracts

Introduction: Aggrecan, encoded by the ACAN gene, is an important component in the cartilage extracellular matrix. Mutations in the ACAN gene have been associated with idiopathic and familial short stature in the recent years. Bone age (BA) is often advanced, although it can be delayed or normal. Patients can have dysmorphic features like broad forehead, midfacial hypoplasia, prognathism, posteriorly rotated ears, broad and short thumbs. Bone and joint problems can be present. Despite that the growth hormone-IGF-1 axis is usually normal, growth hormone (GH) has been successfully used for treatment with or without gonadotropin releasing hormone agonists (GnRHa). We report a patient with familial short stature due to ACAN gene mutation.

Case Report: A 4.3-year-old girl presented for the first time with short stature. She was the first child from an in vitro pregnancy. The mother had uncontrolled hypertension during pregnancy. At 4 months of gestation cerclage was performed and intrauterine growth retardation was established on ultrasound. Prenatal genetic testing was performed which was normal. Placental abruption led to emergency delivery at 34+5 g.w. The patient was born small for gestational age (SGA) with weight 1300 g (-2.6 SDS), length 38 cm (-2.63 SDS) and head circumference 28 cm (-2.19 SDS, Fenton charts). By 1 year of age her height reached the 3rd percentile but after 3 years it dropped below the 3rd percentile. Her father (152.9 cm) and mother (147.0 cm) are short while there are both very short and very tall relatives at father’s side followed three generations back. At first presentation the patient’s height was 93.3 cm (-2.62 SDS, https://www.cdc.gov/growthcharts/) and weight was 12.5 kg (-2.92 SDS). She had proportionate short stature, midfacial hypoplasia and short and broad thumbs. Her BA was 5.2 years (1.2 SDS, Greulich&Pyle by BoneXpert). Hormonal tests were unremarkable. On follow-up at 9.1 years her height was 117.5 cm (-2.9 SDS), weight was 21.5 kg (-2.21 SDS) and BA was 9.26 years (0.41 SDS). Hormonal tests were again normal. A brain MRI was performed which was unremarkable. Genetic analysis revealed a heterozygous mutation in the ACAN gene (c.6972G>A (pTrp2324)) inherited from the father. Due to her short stature the patient is indicated for GH treatment.

Conclusion: We describe a patient born SGA with familial short stature due to ACAN gene mutation. This is the first reported case in Bulgaria. Based on previous reports for treatment effectiveness, GH treatment is offered.