In 2001 the FDA announced a new regulatory scheme called SMART (the System to Manage Accutane Related Teratogenicity) that required Roche to provide defined training materials to doctors, and for doctors to sign and return a letter to Roche acknowledging that they had reviewed the training materials, for Roche to then send stickers to doctors, which doctors would have to place on prescriptions they give people after they have confirmed a negative pregnancy test; prescriptions could only be written for 30 days and could not be renewed, thus requiring a new pregnancy test for each prescription.In February 2002, Roches patents for isotretinoin expired, and there are now many other companies selling cheaper generic versions of the drug. On June 29, 2009, Roche Pharmaceuticals, the original creator and distributor of isotretinoin, officially discontinued both the manufacture and distribution of their Accutane brand in the United States due to what the company described as business reasons related to low market share (below 5%), coupled with the high cost of defending personal injury lawsuits brought by some people who took the drug. Generic isotretinoin will remain available in the United States through various manufacturers. Roche USA continues to defend Accutane and claims to have treated over 13 million people since its introduction in 1982. F. Hoffmann-La Roche Ltd. apparently will continue to manufacture and distribute Roaccutane outside of the United States.Among others, actor James Marshall sued Roche over allegedly Accutane-related disease that resulted in removal of his colon.
There are typically language and walking delays, and those affected have very low muscle tone and decreased reflexes. They may have neural tube defects such as lipomyelomeningocele (a form of spina bifida) or may have syringomyelia (a cyst in the spinal cord). Those with the syndrome may also have symptoms of dysautonomia (impairments in the autonomic nervous system), including gastrointestinal dysmotility, contributing to gastroesophageal reflux disease, or neurogenic bladder dysfunction, in which bladder control is limited. Dysautonomia has also led to high pain tolerance and reduced sweating in some patients. Some of those with the syndrome have been found to have an underdeveloped corpus callosum, the main band of white matter that connects the two cerebral hemispheres. Skeletal
Okamoto syndrome patients often have skeletal problems such as scoliosis or hip dysplasia, which can lead to hip dislocation. They may be born with congenital vertebral anomalies; parts of the spine may be fused and fail to segment. There may also be extra vertebrae in the lower back. Some of those affected have been reported to have premature fusion of the skull bones (craniosynostosis), particularly those across the midline and at the front of the skull. This has led to an elongated skull shape known as scaphocephaly as well as a ridge on the forehead known as a metopic ridge. Growth
Those affected may be born with low weight and size and may display stunted growth in childhood, although this symptom has been variable and not in every individual with Okamoto syndrome.