Additional dermatologic abnormalities (axillary freckling, localized hypopigmentation, interdigital webbing, hyperelastic skin)
Mild mental retardation is observed in about 30% of those affected by the syndrome
Nystagmus (involuntary eye movements), seizures, or hyposmia (reduced ability to smell) has been documented in a few patients
In 2004, a patient was reported with recurrent upper extremity aneurysms that required surgical repairs. In 2006, a NSML patient was reported with acute myelogenous leukemia.Due to the rarity of the syndrome itself, it is hard to determine whether certain additional diseases are actually part of the syndrome. With a base population of possibly less than one thousand individuals, one or two outlying cases can skew the statistical population very quickly. Pathophysiology
In the two predominant mutations of NSML (Y279C and T468M) the mutations cause a loss of catalytic activity of the SHP2 protein (the gene product of the PTPN11 gene), which is a previously unrecognized behavior for this class of mutations. This interferes with growth factor and related signalling. While further research confirms this mechanism, additional research is needed to determine how this relates to all of the observed effects of NSML. Diagnosis
The presence of the disease can be confirmed with a genetic test. In a study of 10 infants with clinical indications of NSML prior to their first birthday, 8 (80%) patients were confirmed to have the suspected mutation. An additional patient with the suspected mutation was subsequently found to have NF1, following evaluation of the mother.There are 5 identified allelic variants responsible for NSML.
See also
Neurofibromatosis
Noonan syndrome

References
External links

NSML at NIH/UW GeneTests
Gorlins syndrome II at Who Named It? DermAtlas 981603547
Dermnetnz
DermIS