ESPE Abstracts

Introduction: Noonan syndrome-Neurofibromatosis type 1 (NSNF) is a genetic disorder characterized with clinical features of both Noonan syndrome (NS) and neurofibromatosis type 1 (NF1). Recombinant human growth hormone (rhGH) has been widely used in NS patients as well as in some patients with NF1 but there are only a few published cases of rhGH treated NSNF patients. We report a patient with NSNF with short stature who started rhGH treatment with subsequent persistent leukocytosis.

Case report: A 4-year old girl presented for the first time with short stature. She was previously diagnosed with NSNF based on her typical NS phenotype (relative macrocephaly, low set ears, low posterior hairline, hypertelorism, short neck, broad chest with widely spaced nipples and lower pectus excavatum) and a proven mutation in the NF1 gene inherited from her mother (Exon 29: c.3884C>T heterozygous (P.Thr1295lle). At presentation to us her height was 93.2 cm (-1.97 SDS) and her weight was 13.8 kg (-1.24 SDS). Bone age (BA) was delayed by 1.6 years (-2.99 SDS, evaluated by the Greulich&Pyle reference, BoneXpert) and IGF-1 was 62 ng/ml (-0.93 SDS). During her evaluation, the blood tests showed leukocytosis with no signs of infection. Blood smear was microscopically evaluated by pediatric hematologists. No abnormalities were found and rhGH treatment was considered safe to initiate. After beginning of the treatment she had multiple outpatient blood tests performed with persistent leukocytosis, some of them during mild upper respiratory tract infections with the characteristics of viral ones, with the highest value being 27.62x109/l. A new blood smear was performed at clinical visit and again no abnormalities were found. Continuation of rhGH treatment was considered safe. Due to the high malignant risk in part of the RASopathy patients and the proliferative effect of rhGH a genetic evaluation for Noonan syndrome and a virtual consultation at the Clinical Patient Management System (CPMS) is underway.

Conclusions: The current case report describes an NSNF patient with short stature who is treated with rhGH. Multiple blood tests showed leukocytosis without signs of infection. Patients with RASopathies are known to have increased risk for malignancy. Due to the well known proliferative activity of rhGH, the safety of rhGH treatment in this patient is carefully monitored.