Endocrine Abstracts

JOINT2702

RASopathies is a multisystem genetic disorder characterized by such clinical manifestations as growth retardation, craniofacial and skeletal anomalies, varying degrees of intellectual disability, congenital heart defects and a predisposition to myeloproliferative disorders. Girl E., 5 years old, from the 2nd pregnancy, during the ultrasound examination at the 1st screening an expansion of the collar area nuchal was revealed, at the 20th week of gestation - chorioangioma of the placenta. The 2nd birth was by cesarean section at the 38th week of gestation. At birth, body weight was 3120 g (0.06SD), body length was 48 cm (-0,35SD), according to the Apgar scale 8/9 points. The early neonatal period was unremarkable. Family history of endocrinopathies is not burdened, target height is 163.5 cm, SDS of target height: 0.025 SD. At 3 months, the girl suffered from mixed-etiology sepsis and iron-deficiency anemia. She is being observed by an ophthalmologist with the following diagnosis: OU - compensated convergent sensory, unilateral OD strabismus, accommodative. High myopia OD. Lesion of the central section of the visual analyzer, partial atrophy of the optic nerve OD>OS. OD - madarosis, trichiasis, deformation of the upper eyelid margin. OS - partial ptosis of the upper eyelid stage 1, compensated. Congenital renal defects are excluded. A functioning oval window up to 2 mm remains. Growth retardation is observed from an early age. Karyotype: 46,XX. During examination at 4 years, blood tests showed IGF-1 - 65.8 ng/ml (SDS IGF-1 - 0.82), no data for deficiency of other tropic hormones were obtained. At the age of 5 years his height was 98.2 cm (- 2.4 SD), his weight was 16.5 kg (BMI +1.1 SD), Tanner 1. Phenotypic features were noticed: low-set ears, left eyelid ptosis, strabismus, scaphocephaly, hoarse voice, short neck, chubby cheeks, dark skin, light, sparse, falling out hair. Bone age corresponded to chronological age. Additional molecular genetic testing was performed: a mutation in the SHOC2 gene (chr10:112724120A>G) was detected in a heterozygous state, leading to a substitution of an amino acid in position 2 of the protein [NM 001324336.1:c.4A>G; p.(Ser2Gly)]]. The presented clinical case demonstrates the classic phenotype of RASopathies with loss of anagen, caused by a pathogenic variant in the SHOC2 gene. The issue of treatment with somatropin remains controversial due to the lack of published randomized clinical trials with long-term observation of patients until the period of achieving final height.