ESPE Abstracts

Introduction: Noonan syndrome (NS) is an autosomal dominant inherited, rare syndrome that occurs as a result of mutation in the PTPN11 gene. The most common mutation in Noonan syndrome occurs in the PTPN11 gene and characterized by short stature, developmental delay, congenital heart disease, renal anomalies, lymphatic malformations, distinctive facial features of NS: downslanting palpebral fissures, epicanthic folds, hypertelorism, low-set ears short neck, wing-like folds on the neck, pectus deformity. Clinical spectrum of NS may differ between causative genes, and some forms have been described as "Noonan-like syndrome with juvenile myelomonocytic leukemia (JMML)”. Below is a clinical case with a newly diagnosed Noonan syndrome in a girl in the Republic of Kazakhstan.

Case Report: A 10-year-old girl applied with the complaint of short stature. On physical examination: the girl exhibits curly, fluffy hair, a broad nose with hypertelorism, a small chin, short neck, wide chest, hypertelorism of nipples, and slender limbs. Auxology: body weight was 16 kg, SDS (-5,08), height was 114,5 cm, SDS (-3,55), height velocity 1,12 cm/year, expected final height 142 cm, body mass index was 12,20 kg/m2, SDS BMI (-3,28), bone age 8 years. Pubertyexamination was compatible with tanner stage 1. US investigation: splenomegaly and uterine hypoplasia. She had been under observation from childhood with a diagnosis of JMML. A bone marrow biopsy performed on November 19, 2014, revealed a markedly cellular marrow, predominantly consisting of granulocytic proliferation. Therapy was provided by 6-mercaptoury, positive dynamics were noted, but due to dyspeptic complications, therapy was canceled. Prednisone therapy was administered; during therapy, the girl became more active, but leukocytosis persisted. The diagnosis of JMML was confirmed and Noonan syndrome was suspected. According to genetic analysis of whole exome sequencing the mutation in the PTPN11 gene was identified at 6-year-old age, which is associated with Noonan syndrome (NS). During hospitalization in pediatric endocrinology department a repeat bone marrow biopsy was performed, no data on oncohematological pathology were identified.

Conclusion: The case shows a rare syndrome that characterized mainly by short stature, stigmas of dysembryogenesis, some types of NS can be associated with JMML. In the absence of timely growth hormone therapy patients with Noonan syndrome have very low expected final height. Our patient was diagnosed Noonan Syndrome, Type 1. Molecular genetic analysis through Sanger sequencing was recommended to identify the detected variant PTPN11:c.218C<Tin the proband and parents. Hormone replacement therapy (GH) at the dosage 0,045 mg/kg/daily was prescribed to the patient.