ESPE Abstracts

Introduction: Skeletal dysplasias associated with short stature are caused by inherited cartilage/bone development defects and are often associated with disproportionate short stature. We will present a case of heterozygous NPR2 variants in a patient with ISS.

Case Report: A 8 years 3 months aged girl with normal perinatal and neonatal periods came for short stature evaluation. The clinical exam showed: 115.5 cm (-2.45 SD), normal weight, phenotype with discrete facial dysmorphism, flat nasal bridge, slightly prominent forehead, hypertelorism, brachydactyly, short limbs; Tanner B1G1P2; delayed bone age of 1.5 year. Family history: father 169 cm, mother 142 cm with similar phenotype (MPH=149 cm, SD -2.20), sister with normal height.

Laboratory investigations: Dyslipidemia, euthyroidism, inhibited prepubertal pituitary-gonadal axis, normal prolactin, cortisol and growth hormone and IGF1 score -0.64 SD. The genetician recommended gene panel for bone dysplasia; Results reveal heterozygous nonsense c.2221C>T mutations in exon 15 of NPR2 gene with pathogenic clinical significance (class 5).

Management and treatment: GH stimulation tests were performed with a normal response.

Even if GH therapy is off-label, few patients have a response to it; larger studies are necessary to establish the efficacy of the treatment on final height in patients with NPR2 heterozygosity. We considered the introduction of Vosorotide treatment which is in clinical trials and is awaiting approval but patients refused This is the first medication that directly targets the pathway in chondrocytes affected by these specific mutations.

Discussion: There are few scientific studies which mention treatment with rhGH

Conclusion: Identification of rare monogenic causes is critical for a variety of reasons. First, identification of a molecular etiology can end the diagnostic work up and provide the family an answer to why their child isn’t growing normally. Second, the genetic diagnosis may alert the clinician to other medical comorbidities. Thirdly, determination of a molecular etiology is invaluable for genetic counseling. Finally, genetic etiology may have implications for therapy.