Charcot-Marie-Tooth Disease, Type 5 / Arts syndrome (PRPS1)
Pathogenic variants in the gene PRPS1 cause several different overlapping disorders. The two main disorders are known as Charcot-Marie-Tooth disease, type 5 and Arts syndrome. Charcot-Marie-Tooth disease, type 5 is characterized by degenerative disease of the peripheral nerves (occurring between the ages of 5 and 12), damage to the optic nerve (occurring between the ages of 7 and 20), and bilateral profound sensorineural hearing loss (occurring prelingually). Lower extremities will typically be affected first, so patients may initially present with foot drop or gait disturbances. Carrier female patients are not reported to display disease symptoms. Arts syndrome is characterized by hypotonia, ataxia, hearing impairment, intellectual disability, delayed motor development, increased risk of infection, and optic and peripheral neuropathies. All symptoms except the neuropathies develop before the age of 2, while the neuropathies typically begin to affect the patient during early childhood. Carrier female patients have been reported to display some symptoms after 20 years of age, with the most common being hearing impairment. Some patients with a pathogenic PRPS1 variant may only develop hearing loss. The same variant can cause different disease presentations, even within a single family, and therefore the disease severity cannot be predicted based on the variant inherited. Pathogenic PRPS1 variants occur pan-ethnically.
For information about carrier frequency and residual risk, please see the residual risk table.