Page 13 - Clinical variability in Noonan syndrome with emphasison ear and eye

Table 1. Noonan syndrome scoring system
INTRODUCTION
Facial Cardiac
Height
Chest wall Family history Other
Major
typical face dysmorphology
pulmonary valve stenosis, HOCM and/or ECG typical for NS
<3rd centile
pectus carinatum/ excavatum
first-degree relative with definite NS
mental retardation, cryptorchidism and lymphatic dysplasia
Minor
suggestive face dysmorphology other defect
<10th centile
broad thorax
first-degree relative with suggestive NS
either mental retardation, cryptorchidism or lymphatic dysplasia
Definite NS is diagnosed by: (1) typical face dysmorphology +1 other major sign or 2 minor signs, or (2) suggestive face dysmorphology + 2 other major signs or 3 minor signs. HOCM = Hypertrophic obstructive cardiomyopathy. Table adapted from van der Burgt (16).
Prenatal features
Noonan syndrome and other RASopathies should be considered as a possible diagnosis in pregnancies with a normal karyotype and different prenatal ultrasound findings. These ultrasound findings include polyhydramnios, macrosomia, lymphatic dysplasia (including increased nuchal translucency and cystic hygroma), cardiac anomalies and renal anomalies (18). Recognition of common perinatal findings can facilitate an early neonatal diagnosis.
Growth
Approximately 50-70% of the Noonan syndrome patients have short stature but normal height can also be reached (14,19,20). Noonan syndrome-specific growth charts have been described in literature (21-24). Birth length and weight are usually normal (13). In the first year of life growth failure often starts to occur and is considered as an intrinsic growth failure (25). From approximately two to four years until puberty height follows the third percentile (or -2 SDS). The onset of puberty is often delayed and the growth spurt is often delayed and reduced. The bone age has a mean delay of 2 years (14,21). The mean final height described in females is 148.4-153.3 centimeters and in males is 157.4-169.8 centimeters. As bone maturity can be delayed, prolonged growth into the twenties is found (21-23,26,27). Various mechanisms for the short stature are reported. In Noonan syndrome the growth failure is mainly of postnatal character. The intrinsic primary failure is suggested to be due to insufficient growth hormone secretion, growth hormone resistance and dysregulation of the RAS/MAPK signaling pathway (28-30). Growth hormone stimulation tests are reported as normal and height gain in Noonan syndrome patients treated with growth hormone is presented in literature (31)
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