The natural history of Noonan syndrome: a long-term follow-up study.
OBJECTIVE
To define better the adult phenotype and natural history of Noonan syndrome.


METHODS
A prospective observational study of a large cohort.


RESULTS
Data are presented for 112 individuals with Noonan syndrome (mean age 25.3 (range 12-71) years), who were followed up for a mean of 12.02 years. Mutations in PTPN11 were identified in 35% of probands. Ten subjects died during the study interval; three of these deaths were secondary to heart failure associated with hypertrophic cardiomyopathy. Pulmonary stenosis affected 73 (65%) subjects; 42 (58%) required no intervention, nine underwent balloon pulmonary valvuloplasty (three requiring further intervention) and 22 surgical valvuloplasty (three requiring further intervention). Hypertrophic cardiomyopathy affected 21 (19%) patients, which had remitted in two cases, but one subject required cardiac transplant. No subjects died suddenly or had symptoms suggestive of arrhythmia. The mean final adult height was 167.4 cm in males and 152.7 cm in females. Feeding problems in infancy were identified as a predictor of future outcome. The mean age of speaking in two-word phrases was 26 months for those with no feeding difficulties, compared with 39 months for those with severe problems requiring nasogastric feeding. Attendance at a school for children with special needs for the same groups was 12.5% and 58%, respectively. A statement of special educational need had been issued in 44% overall; however, academic achievement was broadly similar to that of the general population.


CONCLUSIONS
Although the morbidity for some patients with Noonan syndrome is low, early predictors of poorer outcome have been identified, which will help ascertain those most in need of intervention.
Shaw
A C
AC
Medical Genetics Unit, LG Floor, Jenner Wing, St George's, University of London, Cranmer Terrace, London, UK. adam.shaw@nhs.net
Kalidas
K
K
Crosby
A H
AH
Jeffery
S
S
Patton
M A
MA
D000015:Abnormalities, Multiple / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D001827:Body Height; D002423:Cause of Death; D002648:Child; D004522:Educational Status; D004651:Employment; D005260:Female; D005500:Follow-Up Studies; D006128:Growth; D006330:Heart Defects, Congenital / Q000235:genetics / Q000628:therapy; D006801:Humans; D007223:Infant; D007227:Infant Nutritional Physiological Phenomena; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009634:Noonan Syndrome / Q000175:diagnosis* / Q000503:physiopathology / Q000534:rehabilitation; D010641:Phenotype; D011379:Prognosis; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases