1. Motor and sensory neuropathy.
This has been classified based on age of onset and severity as a number of phenotypes:
Childhood onset, Spinal muscular atrophy (SMA)
Childhood onset motor and sensory axonal neuropathy (HMSN)
Childhood-onset motor neuron disease/ Juvenile ALS (amyotrophic lateral sclerosis)
Adult onset motor neuron disease/distal hereditary motor neuron disease
Signs and symptoms may include:
• Tongue fasciculations (in infancy)
• Weakness in the distal lower extremities, slowly progressing to the distal upper limbs
• Gait disturbance
• Muscular atrophy
• Pyramidal signs, including brisk tendon reflexes, without bulbar, respiratory or cognitive involvement
• Normal intellectual development
2. Microcephaly and structural brain anomalies.
Manifestations include:
• Severe congenital microcephaly, which can be progressive
• Pontocerebellar hypoplasia (not necessarily congenital)
• Gyration defects
• Ataxia
VRK1