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.
This region appears to control the epipharyngeal, intrinsic laryngeal and respiratory muscles, and the combined activity of these muscles serve as the basis for the generation of a sneeze.The sneeze reflex involves contraction of a number of different muscles and muscle groups throughout the body, typically including the eyelids. The common suggestion that it is impossible to sneeze with ones eyes open is, however, inaccurate. Other than irritating foreign particles, allergies or possible illness, another stimulus is sudden exposure to bright light – a condition known as photic sneeze reflex (PSR). Walking out of a dark building into sunshine may trigger PSR, or the ACHOO (autosomal dominant compulsive helio-ophthalmic outbursts of sneezing) syndrome as its also called. The tendency to sneeze upon exposure to bright light is an autosomal dominant trait and affects 18-35% of the human population. A rarer trigger, observed in some individuals, is the fullness of the stomach immediately after a large meal. This is known as snatiation and is regarded as a medical disorder passed along genetically as an autosomal dominant trait. Epidemiology
While generally harmless in healthy individuals, sneezes spread disease through the infectious aerosol droplets, commonly ranging from 0.5 to 5 µm. A sneeze can produce 40,000 droplets. To reduce the possibility of thus spreading disease (such as the flu), one holds the forearm, the inside of the elbow, a tissue or a handkerchief in front of ones mouth and nose when sneezing.