Furthermore, the heights of children affected by NF-1 have been shown to increase normally until puberty, after which increases in height lessen when compared to healthy counterparts. This eventually causes a shorter stature than expected in individuals with NF-1. Cancer
Cancer can arise in the form of malignant peripheral nerve sheath tumor resulting from malignant degeneration of a plexiform neurofibroma. Frequency. A plexiform neurofibroma has a lifetime risk of 8–12% of transformation into a malignant tumor. Diagnosis. MRI. Treatment. Surgery (primary), radiation therapy. Mortality. Malignant nerve sheath tumor was the main cause of death (60%) in a study of 1895 patients with NF-1 from France in the time period 1980–2006 indicated excess mortality in NF-1 patients compared to the general population. The cause of death was available for 58 (86.6%) patients. The study found excess mortality occurred among patients aged 10 to 40 years. Significant excess mortality was found in both males and females. Cause
Neurofibromin 1 gene
NF-1 is a microdeletion syndrome caused by a mutation of a gene located on chromosomal segment 17q11.2 on the long arm of chromosome 17 which encodes a protein known as neurofibromin (not to be confused with the disorder itself) which plays a role in cell signaling. The Neurofibromin 1 gene is a negative regulator of the Ras oncogene signal transduction pathway. It stimulates the GTPase activity of Ras. It shows greater affinity for RAS p21 protein activator 1, but lower specific activity. The mRNA for this gene is subject to RNA editing (CGA->UGA->Arg1306Term) resulting in premature translation termination.
The mice were also smaller, had less developed organs and had higher postnatal mortality (30%). The median lifespan of the mice that survived was less than 50% that of wild-type mice. However, blood cancers had not yet been detected in any of the Okamoto syndrome patients as of 2018.Mutations in both copies of HNRNPK are embryonic lethal in mice. Mice with both copies of the gene knocked out die before the 14th day of embryonic development. Diagnosis
The condition has usually been diagnosed based on the physical symptoms and confirmed by genetic testing. Methods have included whole exome sequencing and comparative genomic hybridization (for microdeletions). Sanger sequencing can confirm the nature of the mutation. Treatment
Treatment is focussed on the symptoms. Atrial or ventricular septal defects are usually treated with observation but can be surgically corrected in severe cases. Some patients have been able to use sign language or assistive language devices to facilitate communication. Prognosis
The prognosis of the disorder is not yet fully known. A minority of patients have died in infancy due to complications from their urinary system defects, including infections in Okamotos first two patients, however most have lived through childhood and into adolescence. Motor and language skills typically improve as the patient ages. The prognosis in adulthood is not yet known, due to the lack of known patients in this age group.As an autosomal dominant condition, there is little risk of recurrence in future conceptions from unaffected parents.