Mutations in any of the genes disrupt this process to cause a variety of syndromes depending on the type of mutation and other factors. It remains unclear how these genetic changes cause the death of cells in the optic nerve and lead to the specific features of Leber hereditary optic neuropathy. Pathophysiology
The eye pathology is limited to the retinal ganglion cell layer, especially the maculopapillary bundle. Degeneration is evident from the retinal ganglion cell bodies to the axonal pathways leading to the lateral geniculate nuclei. Experimental evidence reveals impaired glutamate transport and increased reactive oxygen species (ROS) causing apoptosis of retinal ganglion cells. Also, experiments suggest that normal, non-LHON-affected retinal ganglion cells produce less of the potent superoxide radical than other normal central nervous system neurons. Viral vector experiments that augment superoxide dismutase 2 in LHON cybrids or LHON animal models or use of exogenous glutathione in LHON cybrids have been shown to rescue LHON-affected retinal ganglion cells from apoptotic death. These experiments may in part explain the death of LHON-affected retinal ganglion cells in preference to other central nervous system neurons that also carry LHON-affected mitochondria. Diagnosis
Without a known family history of LHON the diagnosis usually requires a neuro-ophthalmological evaluation and blood testing for mitochondrial DNA assessment. It is important to exclude other possible causes of vision loss and associated syndromes such as heart electrical conduction system abnormalities. Treatment
The prognosis for those left untreated is almost always continued significant visual loss in both eyes.
Christianson syndrome is an X linked syndrome associated with intellectual disability, microcephaly, seizures, ataxia and absent speech. Presentation
Onset of symptoms is normally within the first year of life with truncal ataxia and seizures. The head is small (microcephaly). Common facial abnormalities include:
Long narrow face
Prominent nose
Prominent jaw
Large ears
Open mouth
Thick eyebrowsOther common features include:
Uncontrolled drooling
Abnormal eye movementsThe associated intellectual disability is usually in the profound range. Those affected often have a happy demeanor with frequent smiling and spontaneous laughter. Genetics
This condition is caused by mutations in the SLC9A6 gene. This gene is located on the long arm of the X chromosome (Xq26.3). The gene encodes a sodium/hydrogen exchanger located in the endosomes. Mutations in this gene cause a rise in the pH of the endosomes.How this causes the clinical features is not known presently. The inheritance of this condition is X-linked dominant. Diagnosis
The diagnosis may be suspected on clinical grounds.It is made by sequencing the SLC9A6 gene. Differential diagnosis
Angelman syndrome
Spinocerebellar ataxia type 29

Management
There is presently no curative treatment. Management is supportive. Epidemiology
The prevalence is not known but this is considered to be a rare disease. History
This condition was first described in 1999. The causative mutation was discovered in 2008. == References ==