The natural history of Noonan syndrome: a long-term follow-up study

• Published in: Archives of disease in childhood Vol. 92; no. 2; pp. 128 - 132
• Main Authors: Shaw, A C, Kalidas, K, Crosby, A H, Jeffery, S, Patton, M A
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health 01-02-2007; BMJ; BMJ Publishing Group Ltd; BMJ Publishing Group LTD; BMJ Group
• Subjects: Abnormalities, Multiple - genetics; Adolescent; Adult; Aged; Biological and medical sciences; Body Height; Breast cancer; Cardiomyopathy; Cardiovascular disease; Cause of Death; Cerebral palsy; Child; Congenital diseases; Death; Diseases of the osteoarticular system; Educational Status; Employment; Enteral nutrition; Family (Sociological Unit); Fatalities; Female; Follow-Up Studies; Followup Studies; General aspects; Genetic aspects; Genotype & phenotype; Growth; HCM; Heart; Heart Defects, Congenital - genetics; Heart Defects, Congenital - therapy; Humans; hypertrophic cardiomyopathy; Infant; Infant Nutritional Physiological Phenomena; Intracellular Signaling Peptides and Proteins - genetics; Male; Males; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical sciences; Middle Aged; Miscellaneous; Mutation; Noonan syndrome; Noonan Syndrome - diagnosis; Noonan Syndrome - physiopathology; Noonan Syndrome - rehabilitation; Observational studies; Original; Patient outcomes; Patients; Phenotype; Prevention and actions; Prognosis; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatases - genetics; Public health. Hygiene; Public health. Hygiene-occupational medicine; SDS; Standard deviation; standard deviation score; Studies; Traffic Safety; United Kingdom > UK; Human; Pediatrics; Nervous system diseases; Pathogenesis; Diseases of the osteoarticular system; Cardiovascular disease; Review; Long term; Genetic disease; Follow up study; Cohort study; Noonan syndrome; Adult; Evolution; Osteochondrodysplasia; Child; Public health
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/adc.2006.104547

Objective: To define better the adult phenotype and natural history of Noonan syndrome. Design: 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. Implications: 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.