Endocrine Abstracts

JOINT3680

Introduction: Cartilage oligomeric matrix protein (COMP) is a pentameric extracellular matrix glycoprotein that is critical for collagen formation and extracellular matrix stability. Mutations in the COMP gene lead to impaired extracellular matrix stability, secondary chondrocyte apoptosis, and two rare skeletal dysplasias: pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED). Here, we present a case of a patient diagnosed with a COMP gene mutation, who was followed in our clinic due to short stature.

Case Report: A 6-year-7-month-old girl was referred to our clinic by the rheumatology department for short stature. Her medical history revealed that she was born at 39+4weeks of gestation and gestation weight was 2660grams, she had always been shorter than her peers, and was under follow-up for Familial Mediterranean Fever(FMF) with no attacks after colchicine treatment. There was no consanguinity between her parents. The mother’s height was measured as 150.9cm, and the father’s height as 165cm(mid-parental height: 151.4cm). Physical examination showed a body weight of 16.5kg(-1.94SD), height of 106.5cm(-2.5SD), and Tanner stage 1 puberty. Laboratory investigations revealed an IGF-1 level of 152ng/ml (+1SD), IGFBP3 level of 4281ng/ml (0/+1SD), normal thyroid function tests, negative celiac antibodies, and a bone age of 6years and 9months. Growth hormone stimulation testing demonstrated a peak response of 20.4ng/ml. The patient was monitored for growth velocity, which was found to be 3.7cm/year.Subsequently, somatropin therapy was initiated. Under treatment, growth velocities were observed as 7cm/year in the first year,8.3cm/year in the second year, and 7.6cm/year in the third year, with IGF-1 levels at +1SD. Chromosome analysis showed 46,XX, and a genetic panel for short stature identified a heterozygous c.1767C>A (p.Asn589Lys) variant in the COMP gene, classified as a variant of uncertain significance (VUS) close to pathogenicity. As the variant was evaluated as potentially pathogenic and the patient’s final bone age was consistent with 14years, somatropin therapy was discontinued. At her last follow-up, the patient was 12years old with a bone age of 14years, a body weight of 35.9kg (-1.28SD), height of 138.1cm (-2.35SD), and Tanner stage 4puberty. The patient’s growth velocity declined due to the discontinuation of treatment and her untreated growth velocity was 2.4cm/year.

Discussion/Conclusion: Although COMP gene mutations typically lead to two rare skeletal dysplasias, they can present as idiopathic short stature without overt skeletal dysplasia findings. COMP, which plays a role in extracellular matrix stabilization, has been shown to correlate with serum levels of chondrocytes, growth hormone, and IGF-1. Therefore, growth hormone therapy may contribute to final height outcomes in short stature cases with COMP gene mutations.