More than half of our patients fulfilled the European Federation of Neurological Societies (EFNS) diagnostic criteria for CIDP indicating that distinction between Neuro-Sjögren and other causes of neuropathy such as CIDP is challenging.
Almost 90% of them could be alternatively classified as responsible for: (a) an early-onset phenotype, with first limitations starting before 3 years (2.5 ± 0.50 years), motor milestones delays, frequently severe course and upper limb MNCVs below 15 m/s; (b) late-onset neuropathy, with mean age of onset of 42.8 ± 1.5 years and mean upper limbs motor nerve conduction velocities (MNCVs) of 47.2 ± 1.4 m/s; (c) a phenotype more similar to typical CMT1Aneuropathy, with onset during the 2nd decade, MNCV in the range of 15-30 m/s and slowly progressive course.
Hereditary Neuropathy with liability to Pressure Palsies (HNPP) is an autosomal dominant neuropathy, associated with deletion of the Peripheral Myelin Protein-22 (PMP-22) gene, causing recurrent painless palsies with age of onset between 10 and 30 years old.
Zhao et al., in this issue of the JCI, successfully utilized antisense oligonucleotides (ASOs) to reduce PMP22 and ameliorated neuropathy in both mouse and rat models of CMT1A.
Overexpression of Pmp22 in rodent models recapitulates several aspects of neuropathy, and reduction of Pmp22 in such models results in amelioration of the neuropathy phenotype.
We propose that lipid supplementation is an easily translatable potential therapeutic approach in CMT1A and possibly other dysmyelinating neuropathies.
Consequently, several ultrasound scoring tools were applied, i.e., the nerve pattern classification according to Padua et al. in all patients with CIDP and variants, the Bochum ultrasound score (BUS) and the neuritis ultrasound protocol in immune-mediated neuritis, the ultrasound pattern sum score, the homogeneity score, and the nerve enlargement distribution score in all neuropathies if possible.For all scores good accuracy was found.
This study delineates the clinical and molecular features of PMP22 point mutations in Taiwan, and emphasizes their roles in demyelinating CMT or HNPP-like neuropathy.
Recurrent focal neuropathy with liability to pressure palsies is a relatively frequent autosomal-dominant demyelinating neuropathy linked to peripheral myelin protein 22 (PMP22) gene deletions.
However, non-CMT1Aneuropathy patients rarely have causative copy-number variations, and to date, autosomal-recessive disease has not been associated with copy-number variation as a mutational mechanism.
However, whether or not VCR exacerbates neuropathies through mutations in other CMT-associated genes besides PMP22 duplication has not been well studied.
Although PMP22 point mutations are not common, our findings highlight the importance of sequencing the PMP22 gene in patients with variable CMT phenotypes and also confirm that the PMP22Thr118Met mutation is associated with a neuropathy albeit with reduced penetrance.
Duplication or deletion of PMP22 causes the most common autosomal dominant neuropathies, Charcot-Marie-Tooth disease type 1A or hereditary neuropathy with liability to pressure palsies.
Charcot-Marie-Tooth 1A (CMT1A) neuropathy, the most common inherited peripheral neuropathy, is primarily caused by a gene duplication for the peripheral myelin protein-22 (PMP22).
Each of these CNVs includes either the entire PMP22 gene, or exon(s) only, or ultraconserved potential regulatory sequences upstream of PMP22, further supporting the contention that PMP22 is the critical gene mediating the neuropathy phenotypes associated with 17p12 rearrangements.
It is concluded that the MLPA allows accurate detection of PMP22 gene duplications/deletions and could be used for the molecular diagnosis of these two neuropathies.