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.
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.