ESPE Abstracts

Introduction: Short stature is one of the main reasons leading a patient to the attention of the Pediatric Endocrinologist. It is important to know the possible causes of short stature, even the rarest genetic mutations associated with short stature. Although the diagnosis of short stature is primarily the result of physical examination with anthropometric measurements, biochemical and radiological data, genetical tests currently play an important role.

Case Presentation: We present the case of a 2.5-year-old boy who came to our attention for growth failure with a slowing growth rate in the last year. He was delivered at full term by an uneventful spontaneous vaginal delivery and his birth weight was 2820 g (AGA). Physical examination revealed a healthy infant with waddling gait and apparent disproportionately short limbs; his stature and weight were under 3rd percentile for his age (-2.87sds and -3.91sds, respectively) and under mid-parental height (delta target -1,87sds). Bilateral severe genu varum, sabre tibia and symmetrical limitation of hip abduction were reported. Basal blood tests including bone metabolism and IGF-1 levels were performed and resulted normal. Moreover, total body RX showed severe bone age delay (bone age of about 6 months) with flared appearance of the radio-ulnar and tibio-femoral metaphyses, suggesting a diagnosis of rickets. Biochemical tests about bone metabolism revealed increased values of phosphoremia and phosphorus tubular reabsorption and normal values of total calcemia and urinary calcium/creatinine ratio. Moreover, genetic panel of rickets was negative.

Results: The NGS analysis of short stature showed the probably pathogenic variant c.1336G>A in heterozygosity in exon 13 of the COMP gene, described in the literature in patients with pseudoachondroplasia and multiple epiphyseal dysplasia with autosomal dominant inheritance. In addition, a variant of uncertain significance in heterozygosity was reported in exon 2 of the IGFALS gene. Biallelic variants of this gene have been associated in the literature with short stature due to primary acid-labile subunit deficiency. Genetic tests on the patient's parents are still pending.

Conclusion: The patient is currently on clinical follow-up. Few cases of paediatric patients with COMP gene mutation have been described in the literature, so further studies are needed to better define the clinical alterations associated with this variant and the correct management.