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Noonan syndrome patients with short stature at a single paediatric endocrinology centre

Yana Deyanova, Violeta Iotova, Milena Stoyanova, Irina Halvadzhiyan, Rositsa Stoicheva, Kaloyan Tsochev, Vilhelm Mladenov, Yuliya Bazdarska, Nikolinka Yordanova, Sonya Galcheva, Vesselin Boyadzhiev, Martin Zenker

Abstract

Introduction: Noonan syndrome (NS) is caused by mutations in RAS/MAPK signalling pathway genes. Growth hormone (GH) treatment is an established yet not fully standardized treatment. 

Aim: The aim of this article is to assess the first 2 years of GH treatment in NS patients at a single centre.

Patients and Methods: A total of 20 (16 males) NS clinically diagnosed regularly followed patients participated (2011–2020). Of these, 9 (45%) had cardiac defects, and 8 (40%) had short stature. Growth hormone deficiency (GHD) was confirmed in 5 patients who started GH treatment, and 2 were treated as short, small for gestational age children. Patients underwent anthropometry, clinical, laboratory and imaging investigations.

Results: The mean age at NS diagnosis was 7.8 ± 3.4 years (1.3 ÷ 10.5), and at GH start 9.1 ± 1.5 years. At GH start, SDSheight was -3.42±0.58 (-4.1 ÷ -2.6), SDSweight -3.07 ± 0.58 (-3.73 ÷ -2.27), and SDSIGF1 -1.12 ± 0.98 (-2.44 ÷ 0.25). The mean BA at diagnosis was delayed by 2.6 ± 0.9 years. The GH starting dose was 0.035 ± 0.005 mg/kg/d, and changed little thereafter.

The growth velocity for the 1st year of treatment was 8.9 ± 1.4 cm, and for the 2nd year 6.9±1.1 cm. The first year ΔSDSheight was 0.72 (p = 0.002), ΔSDSweight was 0.83 (p = 0.025), the 2nd year increments being insignificant. The 1st and 2nd year ΔSDSIGF1 were 1.70 (p = 0.007) and 0.25 (n.s.), resp. Bone age remained significantly delayed. No treatment side effects were observed.

Conclusion: Our study showed that GH-treated NS patients follow the general growth patterns. In order to improve outcomes, the treatment should be further standardized.


Keywords

Noonan syndrome; growth hormone treatment; growth velocity; height gain

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DOI: http://dx.doi.org/10.14748/ssm.v54i2.8166
About The Authors

Yana Deyanova
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital

Violeta Iotova
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital;

Department of Pediatrics, Faculty of Medicine

Milena Stoyanova
Medical University of Varna
Bulgaria

Deparment of Medical Genetics, Faculty of Medicine

Irina Halvadzhiyan
Medical University of Pleven
Bulgaria

Deparment of Pediatrics, Faculty of Medicine

Rositsa Stoicheva
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital

Kaloyan Tsochev
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital;

Department of Pediatrics, Faculty of Medicine

Vilhelm Mladenov
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital;

Department of Pediatrics, Faculty of Medicine

Yuliya Bazdarska
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital;

Department of Pediatrics, Faculty of Medicine

Nikolinka Yordanova
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital;

Department of Pediatrics, Faculty of Medicine

Sonya Galcheva
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital;

Department of Pediatrics, Faculty of Medicine

Vesselin Boyadzhiev
Medical University of Varna
Bulgaria

Department of Pediatrics, St. Marina University Hospital;

Department of Pediatrics, Faculty of Medicine

Martin Zenker
Institute of Human Genetics, University Hospital Magdeburg
Germany

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