Late-onset spinal motor neuronopathy – A common form of dominant SMA

CHCHD10 mutations and motor neuron disease: the distribution in Finnish patients

“…At least mutations in HSPB1 , MFN2 and DYNC1H1 do not cause distinct entities but a continuum of phenotypes ranging from SMA to CMT2 20–22. As we have reported previously, SNAP reductions may occur in patients with SMAJ,5 6 despite almost no clinical evidence of sensory dysfunction. In our experience, patients with SMAJ typically show clinical and/or EMG findings in a proximal and distal distribution already at the initial investigations, in contrast to CMT2, where disease progression to proximal muscles is a late phenomenon.…”

“…Electromyography (EMG) and muscle biopsy display widespread neurogenic findings and a proportion of patients show sensory abnormalities. Muscle weakness and atrophy appear much later in the disease course, and patients have remained ambulant for several decades and their life expectancy is within normal range 4 5. SMAJ is caused by a dominant CHCHD10 mutation c.197G>T p.G66V, a founder mutation in the Finnish population 6.…”

Spontaneous activity in electromyography may differentiate certain benign lower motor neuron disease forms from amyotrophic lateral sclerosis

“…The clinical features of SMAJ patients, apart from electromyographical details, have been described elsewhere [13,20,21]. In short, cramping and fasciculations of muscles were the earliest symptoms in the majority of patients.…”

“…The well preserved clinical motor function of SMAJ patients contrasts with often pronounced symptoms due to fasciculations, myalgic cramps, and widely distributed EMG findings of denervation [13,20,21]. Both spinal and bulbar muscular atrophy (SBMA) and SMAJ patients may show signs of active, chronic denervation in all body regions, and both diseases have an age-of-onset overlapping with amyotrophic lateral sclerosis (ALS).…”

“…Both spinal and bulbar muscular atrophy (SBMA) and SMAJ patients may show signs of active, chronic denervation in all body regions, and both diseases have an age-of-onset overlapping with amyotrophic lateral sclerosis (ALS). This has led to an initial false ALS diagnosis in many SMAJ and SBMA patients [19][20][21] with very harmful psychological and other consequences. Recent molecular genetic developments complicate the clinical management, as another mutation (p.S59L) in the same CHCHD10 gene may cause ALS and frontotemporal dementia, a phenotype markedly different from SMAJ [2].…”