ESPE Abstracts

Introduction: Short stature is a common reason for seeking medical care in childhood. However, clinical variability and genetic heterogeneity don`t allow to identify the immediate cause in a significant part of patients.

Materials and Methods: Patient L., 11.5 years old, complained of growth retardation. A boy from the 3rd pregnancy, which occurred against the background of gestosis, SGA. Delivery 1, by emergency caesarean section at 32-33 weeks of gestation. At birth, body weight was 1150g (SDS -9.9), body length 37 cm (SDS -3.16). Development at 1 year of life with delayed motor and psychomotor development; there was a delay in speech development. At the age of 5 he underwent surgery for sagittal craniosynostosis. Observed with a diagnosis of sensorineural hearing loss of the 3rd degree, condition after hearing prosthetics; scoliosis, deformity of the vertebral bodies; minor cardiac abnormalities. Mother's height is 147cm, father's height is 170cm, and target height is 166cm, (SDS -1.5). Delayed physical development was noted from birth. Karyotype 46ХY. According to clinical examination height 117.3 cm, SDS – 4.4, weight 22 kg, SDS BMI – 0.85. Tanner (G 1, P1), testicles in the scrotum, volume testes D=S=4 ml. Stigmas of dysembryogenesis were revealed: high forehead, shortening of 4-5 fingers, keeled chest, scoliosis, flat-valgus feet. During the examination, bone age corresponded to chronological age. In blood tests, IGF-1 corresponded to normal values (SDS IGF-1 +0.3), and no deficiency of other pituitary tropic hormones was detected.

Results: Two heterozygous missense variants were discovered in the NPR2 gene (NM_003995.4): the previously undescribed c.2122T>C (p.Tyr708His) and c.2870G>A (p.Arg957His), previously registered in the HGMD database (CM2111042). Segregation in the family was analyzed using Sanger sequencing: compound-heterozygous state of detected missense variants in the NPR2 gene was confirmed: variant c.2122T>C (p.Tyr708His) inherited from the father, variant c.2870G>A (p.Arg957His) – from the mother. Thus, the molecular genetic cause of short stature associated with the NPR2 gene has been verified—acromesomelic dysplasia of the Maroto type (OMIM: 602875) with an autosomal recessive type of inheritance. Treatment with somatropin was prescribed.

Conclusion: The polyetiological nature of short stature in pediatric practice requires advanced methods of molecular genetic research - the use of targeted panels, whole-exome and whole-genome sequencing. Identification of the causative variant allows to verify the diagnosis, to determine further monitoring tactics and to start treatment on time, as well as make a prognosis for the family’s health.