SIGMAR1 mutation should be included in the diagnostic panel of a dHMN, especially if there are co-existing pyramidal signs and autosomal recessive inheritance.
We suggest that coding sequence mutations in SIGMAR1 present clinically with a combination of dHMN and pyramidal tract signs, with or without spasticity, in the lower limbs.
Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively).
The most predominant mutations in CYP27A1 were c.410G > A and c.379C > T, and the most common clinical manifestations were pyramidal signs, xanthomatosis, cerebellar ataxia, and cognitive impairment.
BSCL2 gene mutations are associated with a wide spectrum of clinical and electrophysiological phenotypes and should be suspected in cases of distal hereditary motor neuropathy with pyramidal signs or early hand involvement.
Duplication of the LMNB1 gene encoding lamin B1 causes adult-onset autosomal-dominant leukodystrophy (ADLD) starting with autonomic symptoms, which are followed by pyramidal signs and ataxia.