Familial idiopathic short stature and beyond: a case-report of a novel heterozygous NPR2 mutation.
Abstract
Background: NPR2 gene encodes for B-type natriuretic peptide receptor (NPR-B), a positive regulator of the growth plate. Recently, heterozygous NPR2 mutations were reported in 2–6% cases of idiopathic short stature (ISS) and 13.6% of familial ISS.
Case report: A 9-years-old boy was referred to our Outpatient Clinic of Pediatric Endocrinology for short stature. Analysis of growth chart revealed severe short stature since early childhood. At first evaluation he presented with a stature of 117.3 cm (-3.20 SDS), below the target height (-2.68 SDS), with normal body proportions and delayed bone age. Some dysmorphic features (small and stubby hands, slightly prominent frontal bosses) were observed. Laboratory investigations ruled out the main causes of short stature. A growth hormone (GH) stimulation test was performed, showing elevated GH levels at baseline (9.781 ng/ml) with low insulin-like growth factor-1 (IGF-1) levels (61.98 ng/ml). GH receptor resistance was therefore excluded. Genetic analysis highlighted a novel heterozygous mutation in the NPR2 gene (c.938del; c.953G>A), inherited from the mother.
Conclusion: Our case-report highlights that ISS represents a diagnosis of exclusion, that can only be formulated after a detailed diagnostic evaluation. The identification of a genetic aetiology in many ISS patients may contribute to better characterize the diagnosis, with potential implications in terms of growth outcome and response to treatment, allowing tailored management besides familial genetic counselling.
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DOI: https://doi.org/10.13129/1828-6550/APMB.112.1.2024.CCS3
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