Together, likely with domains yet to be discovered, neurofibromin regulates many of the pathways responsible for overactive cell proliferation, learning impairments, skeletal defects and plays a role in neuronal development. Inheritance and spontaneous mutation
The mutant gene is transmitted with an autosomal dominant pattern of inheritance, but up to 50% of NF-1 cases arise due to spontaneous mutation. The incidence of NF-1 is about 1 in 3500 live births. Related medical conditions
Mutations in the NF1 gene have been linked to NF-1, juvenile myelomonocytic leukemia and Watson syndrome. A condition with a separate gene mutation but similar Café au lait spots is Legius syndrome, which has a mutation on the SPRED1 gene. Diagnosis
Prenatal testing and prenatal expectations
Prenatal testing may be used to identify the existence of NF-1 in the fetus. For embryos produced via in vitro fertilisation, it is possible via preimplantation genetic diagnosis to screen for NF-1.Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus.While the presence of NF-1 can be identified through prenatal testing the severity with which the condition will be expressed is impossible to determine.People with NF-1 have a 50% percent chance of passing the disorder on to their kids, but people can have a child born with NF-1 when they themselves do not have it. This is caused in a spontaneous change in the genes during pregnancy. Post-natal testing
The National Institutes of Health (NIH) has created specific criteria for the diagnosis of NF-1. Two of these seven "Cardinal Clinical Features" are required for positive diagnosis.
The genes identified in these two syndromes are the nicotinic acetylcholine receptor alpha-4 subunit and potassium voltage-gated channel subfamily KQT member 2 respectively. Mutations in these genes lead to the clinical manifestations found in these disorders. It is theorized that deletions in these regions from the ringed chromosome may lead to epilepsy in affected patient. A similar association between a ring chromosome and an autosomal-dominant disease has been reported for ring 17 chromosome and Miller-Dieker syndrome. The recurrence risk for ring chromosome 20 syndrome is very low. The ring formation is typically not identified in parents, and occurs de novo during pre-natal development. Diagnosis
The ring 20 abnormality may be limited to as few as 5% of cells, so a screen for chromosomal mosaicism is critical. Newer array technology will not detect the ring chromosome and the standard metaphase chromosome analysis has been recommended. A karyotype analysis examining at least 50 cells should be requested to properly detect mosaicism. Treatment
Successful management of seizures plays a key role in improving quality of life. Antiepileptic medications are the main therapies for seizures; however, it appears that seizures in this syndrome do not respond well to drugs. In the cases reported in literature, numerous new and old antiepileptic drugs have been tried, but no one drug appears to be more efficacious than others. Therefore, no recommendations can be made regarding the selection of the most appropriate antiepileptic drug.