For many years mutations of the seipin gene were associated with a loss of function, such as in CGL (see above). However, recent studies show that mutations such as N88S and S90L seem to have a gain-of-toxic-function which may result in autosomal dominant motor neuron diseases and distal hereditary motor neuropathy, such as Silver syndrome and distal hereditary motor neuropathy type V.
Owing to the wide clinical spectrum of these mutations, it has been proposed to collectively refer to seipin-related motor neuron diseases as seipinopathies.
Symptoms can vary and include: developmental regression of motor and cognitive skills in the first years of life leading to death (encephalopathy), muscle weakness and spasticity in lower limbs (spastic paraplegia type XVII), weakness of distal muscles of upper limbs (distal hereditary motor neuropathy type V) as well as wasting of the hand muscles (in both cases). Complex forms of seipinopathies may include deafness, dementia or mental retardation.