ESPE Abstracts

Background: Noonan syndrome (NS) is an autosomal-dominant inherited condition defined clinically by a short stature, specific phenotype, congenital heart disease, bleeding and hematologic abnormalities (particularly leukaemia). There is also a genetic heterogeneity, with all mutations involved in the RAS/mitogen-activated protein (MAP) kinase pathway and with PTPN11 gene mutations counting for almost 50% of patients.

Objective and hypotheses: To describe the case of a newborn girl with antenatal diagnosis of NS and neonatal haematological complication (juvenile myelomonocytic leukemia (JMML)-like picture) raising questions about safety of growth hormone (GH) therapy in such particular situation.

Method: During the intrauterine life, the foetus developed a bilateral pleural effusion. An amniocentesis was performed and the diagnosis of NS (p.G503R c.1507G>C mutation in exon 13 of the PTPN11 gene) was made. The baby was born at 30 weeks of gestation, with 1370 g and 38.5 cm. At the age of 10 days, the peripheral blood profile (leukocytosis – 45.000/mm³ and thrombocytopenia – 70.000/mm³) and the bone marrow smear morphology (myelodysplasia) fulfilled the international criteria for JMML.

Results: The clonality of this myeloproliferation was negative and a spontaneous regression was noted. A regular follow-up was started with the child registered in a European long-term follow-up concerning the risk of malignancy in NS. At the age of 1 year 9 months, the toddler is well-appearing, with characteristic facial appearance and short stature (height is 69,5 cm, on −1 DS on Noonan growth chart). The retrospective diagnosis of NS was made in the mother and maternal grandmother.

Conclusion: Antenatal NS diagnosis provided important clues for early multidisciplinary approach. A myeloproliferative disorder, even with spontaneous resolution, in a child with NS and PTPN11 germline mutation deserves a very close clinical follow-up. GH therapy to promote growth should be considered in relation to the genotype, the stature gain and the potentially amplified tumour risk.