I have an email alert set up with NCBI Pubmed such that I get a prompt when a new study on HNPP is published. Last week this one came through,
Introduction: The first episode of hereditary neuropathy with liability to pressure (HNPP) in childhood is rare.
Material and Methods: We analyzed retrospectively the data of 7 patients with a deletion in PMP22 and onset of symptoms before age 18 years. Direct sequencing of the LITAF gene was performed in patients and family members.
Results: Clinical presentations varied from mononeuropathies to brachial plexopathy, with recurrent episodes in 4 patients. Electrophysiological abnormalities characteristic for HNNP were found in most subjects. Analysis of the LITAF gene revealed an Ile92Val polymorphism in 6 of 7 (86%) probands and 5 of 7 (83%) family members, over 4 greater frequency than in the general population.
Conclusion: Clinical suspicion of HNPP even when nerve conduction study results do not fulfill HNPP criteria should indicate genetic testing. In our patients early-onset HNPP was associated frequently with Isoleucine 92valine LITAF polymorphism. © 2014 Wiley Periodicals, Inc.
Copyright © 2014 Wiley Periodicals, Inc., a Wiley company.
Charcot-Marie-Tooth disease, LITAF, PMP22, childhood hereditary neuropathy, hereditary neuropathy with liability to pressure palsy PMID: 24668782
It took me a while to digest what was being said, but the gist seems to be that early onset HNPP with confirmed deletion of PMP22 gene, is sometimes seen to be the result of a further mutation of the LITAF (lipopolysaccharide-induced-tumour-necrosis-factor-alpha-factor) gene.
Mutations of LITAF gene (sometimes called SIMPLE gene) have previously been shown to cause CMT1C.
Mutations in LITAF may account for a significant proportion of CMT1 patients with previously unknown molecular diagnosis and may define a new mechanism of peripheral nerve perturbation leading to demyelinating neuropathy.
A 2-year-old boy presented with early-onset Charcot-Marie-Tooth disease (CMT). His parents had not been diagnosed previously with CMT, but on careful examination they showed clinical signs of CMT and reduced nerve conduction velocities. Genetic analysis identified the boy as a heterozygote for both a peripheral myelin protein 22 (PMP22) duplication and a mutation in the lipopolysaccharide-induced-tumour-necrosis-factor-alpha-factor (LITAF) gene, whereas each parent only had one mutated CMT gene. This suggests that LITAF mutations can severely affect the CMT phenotype caused by a PMP22 duplication.
Which appears to be a similar situation as the HNPP + LITAF gene study.
The mutations of the LITAF can cause a demyelinating neuropathy classed as CMT1C. But also LITAF mutations can cause an early onset and more severe form of neuropathy in people with both the CMT1A PMP22 Duplication and HNPP PMP22 Deletion.