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More than 97 patients have been described with Lower motor neuron syndrome with late-adult onset to date, all originating from Finland, where the point prevalence estimate rises to 1/8,000 in northern Karelia.

The main early signs generally present after 30 to 40 years of age, and usually include muscle cramps, fasciculations, decreased/absent deep tendon reflexes, elevated serum creatine kinase, and hand tremor. Disease progresses slowly and leads to muscular weakness and mild to moderate atrophy (predominantly affecting the proximal lower limbs, although occasional distal upper limb and abdominal involvement has also been reported). Impaired vibration sensation in the lower limbs may occur later in life, and some patients may develop mild dysphagia. Additional signs and symptoms include myalgia, and fatty degenerative replacement predominantly in the calves and hamstrings muscles. Respiratory functions are usually normal and there are no upper motor neuron signs.

The disease is caused by a pathogenic mutation (p.G66V) in the CHCHD10 gene (22q11.2), encoding a mitochondrial, coiled-coil-helix-coiled-coil-helix protein of unknown function. CHCHD10 is involved in oxidative phosphorylation and possibly takes part in mitochondrial complex function (particularly complex IV), and in maintaining mitochondrial DNA. The exact pathogenic mechanism of this mutation remains poorly understood.

Diagnosis is based on clinical and electromyographic evaluation showing prominent fasciculations and chronic denervation in all limbs and possibly in the trunk, as well as evidence of neurogenic changes on muscle biopsy. Diagnosis is confirmed by identification of a causative mutation on the CHCHD10 gene.

The disorder must be differentiated from other neuromuscular diseases, including autosomal dominant adult-onset proximal spinal muscular atrophy and amyotrophic lateral sclerosis (ALS), due to significant genetic and/or clinical overlap.

Antenatal diagnosis is possible in families with a known disease causing mutation.

The disease follows an autosomal dominant pattern of inheritance. Genetic counseling should be provided to affected families, informing them of the 50% risk of transmission in future pregnancies.

Disease management is mainly symptomatic, as no specific treatment is available to date.

The disease has a relatively mild course, as most patients remain ambulatory for several decades after disease onset and present a normal life expectancy.