Paraspinal neurofibromas and hypertrophic neuropathy in Noonan syndrome with Multiple Lentigines

Noonan syndrome with multiple lentigines, (NSML) formerly known as LEOPARD syndrome, has overlapping features with other RASopathies. Except for neurofibromatosis type 1, other disorders that result from dysregulated RAS/MAPK pathway are not known to be associated with neurogenic tumors. We identified four patients from three families with NSML, progressive neuropathy, enlarged nerves, massive burden of paraspinal neurofibromas and a mutation in the PTP catalytic domain of the PTPN11 gene (p.Thr468Met and p.Thr279Cys). Analysis of hypertrophic nerve did not disclose a second somatic hit in NF1, PTPN11, NF2 or SMARCB1 genes. Neurogenic tumors and hypertrophic neuropathy may be under-recognized manifestations of NSML that would warrant surveillance. Our observation may also have implications for other disorders caused by RAS-pathway dysregulation. (By Drs. Dusica Babovic-Vuksanovic and Erin Conboy, http://jmg.bmj.com/content/early/2015/09/02/jmedgenet-2015-103177 )

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