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

ABSTRACT: 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.

SUBMITTER: Shaw AC

PROVIDER: S-EPMC2083343 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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

Shaw A C AC Kalidas K K Crosby A H AH Jeffery S S Patton M A MA

Archives of disease in childhood 20060921 2

<h4>Objective</h4>To define better the adult phenotype and natural history of Noonan syndrome.<h4>Design</h4>A prospective observational study of a large cohort.<h4>Results</h4>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 hypertr ...[more]

PMID: 16990350

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Project description:BackgroundGreater trochanteric pain syndrome (GTPS) is a musculoskeletal condition which can cause disability and reduce quality of life. However, limited evidence is available on the long-term outcomes of people with GTPS. Our aims were to determine the long-term prevalence of GTPS; to calculate the proportion of people with GTPS who had developed hip osteoarthritis (OA); and to determine the level of function and quality of life, 11-years after initial GTPS diagnosis.MethodsA prospective 11-year natural history study. Two groups [GTPS group (n = 24), asymptomatic control (ASC) group (n = 20)] were evaluated at baseline, 12-months and 11-years. At 11-years all participants completed the modified Harris Hip Score (mHHS), Oswestry Disability Index (ODI) and Assessment of Quality-of-Life questionnaire. At 11-year follow-up 20/24 GTPS and 19/20 ASC participants were clinically assessed for GTPS and hip OA, completed the 10 metre-walk-test, timed up and go, and hip abduction and external rotation strength testing.ResultsAt 11-year follow-up 45.0% of GTPS participants had GTPS compared to 5.3% of ASC participants (p = 0.008), OR [95% CI]: 10.19 [1.95, 104.3], and 35.0% of GTPS participants were clinically diagnosed with hip OA compared to none of the ASC participants (p = 0.002), OR [95% CI]: 21.6, [2.3, 2898.0]. GTPS participants reported more pain and disability than ASC participants via the ODI, mean difference [95% CI]: 6.1 [0.7, 11.6] but not the modified Harris Hip Score, mean difference [95% CI]: -3.3 [-10.3, 3.7]. Both groups had similar levels of quality of life and measures of function.ConclusionsGTPS is a chronic condition: people with GTPS at baseline had twice the odds of being clinically diagnosed with GTPS or hip OA than the control group at 11-years. Further, there appears to be a temporal relationship between GTPS and the development of hip OA. This finding highlights the need to identify effective treatments that address the underlying impairments associated with GTPS. Pain and function results varied depending on the assessment tools used. Between group differences in quality of life seen at baseline are not found at the 11-year follow-up. The small sample size means the results must be considered with caution.Level of evidenceLevel II Natural history Study.

Project description:BackgroundMultiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection.MethodsThis study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features.Findings345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs.InterpretationThyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year.FundingNone.

Dataset Information

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

Publications

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

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