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Natural History of Noonan Syndrome« Back to Volume 23, Issue 3, November 2007 - Table of Contents One-hundred and fifty-one subjects with Noonan syndrome from 123 families were recruited into the Noonan Syndrome Research Group at St George’s University of London Hospital between 1989 and 1991. Between 2001 and 2003 all families were invited to participate in a follow-up assessment which included clinical examination, echocardiography, three-dimensional digital facial photography and analysis of the PTPN11 gene. Of the 151 patients, 34 dropped out of the study and 10 (6.6%) died. The final study cohort comprised 112 individuals (57 males) from 92 families. Seventy of these were fully assessed and 32 partially assessed. The mean age at assessment was 25.3 years and the mean interval for follow-up was 12 years. PTPN analysis was done in 79 individuals; mutations were found in 35%. The mutations were more likely to be found in familial cases (50%). Height SDS at entry into the study was –2.184 and at follow-up was –1.755. Twelve individuals received growth hormone (GH) treatment. There were no statistical differences in the height SDS between those who received and those who had not received GH therapy. Those with PTPN mutations had similar mean height SDS. Final adult height was 167.4 cm (males) and 152.7 cm (females). When the individuals who received GH treatment were excluded, the mean final height increased to 169.8 cm (males) and 153.3 cm (females) as those who received GH were shorter. The final height in those with the PTPN11 mutation was about 4 cm less than the others. Pulmonary stenosis was present in 65% and more prevalent in those with the mutation. No intervention was required in 58% of subjects. Hypertrophic cardiomyopathy was present in 19%; 9 of these subjects also had pulmonary stenosis. Five individuals died from complications related to hypertrophic cardiomyopathy and one person had a cardiac transplant. Feeding difficulties at ascertainment were common; some were associated with developmental speech delay. Approximately 73% of these individuals attended mainstream schools while 27% attended schools for children with learning disabilities (the mutation was equally distributed between the 2 groups); 16% had achieved higher education (this compares with 25% of the UK population). Sixty percent were full-time employed, while 26% were registered as disabled. Orthodontic work had been performed on 51%. Six percent of the individuals had required hormone injections to induce puberty. Puberty was somewhat delayed, starting at 14.5 years (males) and 14 years (females). Of those individuals who attempted to have children, 67% experienced no problems. Easy bruising or bleeding was seen in about 79%, but not associated with any known coagulopathy; prevalence of the PTPN mutation was higher in those with a history of easy bruising. Refractive errors were seen in 71% of the individuals. Lymphedema affected the lower limbs of 2, and scoliosis was present in 13%. Approximately 13% had recurrent seizures; PTPN11 mutations were identified in 2 of those. All subjects, with the exception of 4, had normal hearing at follow-up. The authors stated that their longitudinal follow-up was one of the largest databases on well-characterized Noonan syndrome. However, they have some potential bias in follow-up data because of the individuals who had dropped out. They also pointed out that they could not correlate the PTPN mutations with short stature as others have demonstrated. They found that about 10% of the subjects with mutations had hypertrophic cardiomyopathy. Shaw AC, Kalidas K, Crosby AH, Jeffery S, Patton MA. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child. 2007:92:128-32. Editor’s CommentShaw and colleagues are to be congratulated in following a large group of individuals with Noonan syndrome from childhood through adulthood and final height. Their data do not confirm the data of others with regard to mutations and short stature. Studies from France, Brazil, and Germany have demonstrated different findings with regard to Noonan syndrome. Limal et al1 showed that individuals with the PTPN11 mutation have poor growth and do not respond to GH administration as well as those without the mutation. Ferreira et al2 have also shown reduced GH response to long-term GH treatment. Finally, Binder et al3 have shown that those with SHP-2 mutation have mild GH resistance and also poor GH response. Thus it is not surprising that the individuals treated with GH in the current longitudinal study, although shorter, also ended up shorter than those who had not been treated. Other studies will be needed in order to determine whether higher doses of GH or insulin like growth-factor (IGF)-I treatment4 may enhance final height of those children with Noonan syndrome who have the PTPN11 mutation. William L. Clarke, MD References - (linked to
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
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