Biomaterial Database

The natural history of Noonan syndrome: a long-term follow-up study. 2007

A C Shaw, and K Kalidas, and A H Crosby, and S Jeffery, and M A Patton

Medical Genetics Unit, LG Floor, Jenner Wing, St George's, University of London, Cranmer Terrace, London, UK. adam.shaw@nhs.net

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.

UI	MeSH Term	Description	Entries
D007223	Infant	A child between 1 and 23 months of age.	Infants
D007227	Infant Nutritional Physiological Phenomena	Nutritional physiology of children from birth to 2 years of age.	Infant Nutrition Physiology,Nutrition Physiology, Infant,Complementary Feeding,Infant Nutritional Physiological Phenomenon,Infant Nutritional Physiology,Supplementary Feeding,Complementary Feedings,Feeding, Complementary,Feeding, Supplementary,Feedings, Complementary,Feedings, Supplementary,Nutritional Physiology, Infant,Physiology, Infant Nutrition,Physiology, Infant Nutritional,Supplementary Feedings
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D009634	Noonan Syndrome	A genetically heterogeneous, multifaceted disorder characterized by short stature, webbed neck, ptosis, skeletal malformations, hypertelorism, hormonal imbalance, CRYPTORCHIDISM, multiple cardiac abnormalities (most commonly including PULMONARY VALVE STENOSIS), and some degree of INTELLECTUAL DISABILITY. The phenotype bears similarities to that of TURNER SYNDROME that occurs only in females and has its basis in a 45, X karyotype abnormality. Noonan syndrome occurs in both males and females with a normal karyotype (46,XX and 46,XY). Mutations in a several genes (PTPN11, KRAS, SOS1, NF1 and RAF1) have been associated the NS phenotype. Mutations in PTPN11 are the most common. LEOPARD SYNDROME, a disorder that has clinical features overlapping those of Noonan Syndrome, is also due to mutations in PTPN11. In addition, there is overlap with the syndrome called neurofibromatosis-Noonan syndrome due to mutations in NF1.	Male Turner Syndrome,Turner Syndrome, Male,Familial Turner Syndrome,Female Pseudo-Turner Syndrome,Noonan Syndrome 1,Noonan-Ehmke Syndrome,Pseudo-Ullrich-Turner Syndrome,Turner Phenotype with Normal Karyotype,Turner's Phenotype, Karyotype Normal,Turner's Syndrome, Male,Turner-Like Syndrome,Ullrich-Noonan Syndrome,Female Pseudo Turner Syndrome,Male Turner's Syndrome,Noonan Ehmke Syndrome,Pseudo Ullrich Turner Syndrome,Pseudo-Turner Syndrome, Female,Turner Like Syndrome,Turner Syndrome, Familial,Ullrich Noonan Syndrome
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D011379	Prognosis	A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.	Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D001827	Body Height	The distance from the sole to the crown of the head with body standing on a flat surface and fully extended.	Body Heights,Height, Body,Heights, Body
D002423	Cause of Death	Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint.	Causes of Death,Death Cause,Death Causes