Just a Quickie – e

I’ve seen it written many times, mostly in medical published articles, pubmed etc, that HNPP is mild compared to CMT. I think that’s a nonsense, it’s just too simplistic and does a disservice to both those with HNPP as it does CMT.

Equally one could say that CMT is just a mild form of HNPP, and equally nonsense.

They are both hereditary neuropathies, and CMT1a  and HNPP are caused by mutations of the same gene, Duplication in CMT1a and Deletion in HNPP. They each have unique presentations, and when that is factored with individual variation, the range of signs and symptoms is quite extensive.

Individualised patient care, labels are important but they don’t define the person or the presentation of that persons hereditary neuropathy.

I could be talking nonsense…

Overlapping features of CMT1A and HNPP

Being on the HNPP side of the unequal crossover, we often hear of people who have been tentatively diagnosed with CMT because of their clinical presentation of predominently length dependent distal polyneuropathy and family history. Then later after genetic testing it is found that it isn’t CMT1A but HNPP.
This has been written about in the literature on HNPP and can be found in these studies


Phenotypic Variability Leads to Under-recognition of HNPP


Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11.2-12 deletion.


However, a recent study has noted the overlap from the other side of the duplication/deletion fence, ie someone with confirmed CMT1a who has clear features of pressure palsies, and findings of tomacula on nerve biopsy. As far as I am aware this is the first time this has been noted, although it’s very likely that this has occured before.


Peripheral myelin protein 22 gene duplication with atypical presentations: a new example of the wide spectrum of Charcot-Marie-Tooth 1A disease.

1. Neuromuscul Disord. 2014 Jun;24(6):524-8. doi: 10.1016/j.nmd.2014.03.014. Epub
2014 Apr 13.

Peripheral myelin protein 22 gene duplication with atypical presentations: a new
example of the wide spectrum of Charcot-Marie-Tooth 1A disease.

Mathis S(1), Corcia P(2), Tazir M(3), Camu W(4), Magdelaine C(5), Latour P(6),
Biberon J(2), Guennoc AM(2), Richard L(7), Magy L(7), Funalot B(8), Vallat JM(7).

Author information:
(1)Service de Neurologie, CHU Poitiers, Université de Poitiers, 2 rue de la
Milétrie, 86021 Poitiers, France. Electronic address:
(2)Service de Neurologie, CHU Tours, 2 boulevard Tonnellé, 37044 Tours, France.
(3)Laboratoire de Recherche de Neurosciences, Université d’Alger, Service de
Neurologie, Centre Hospitalier Universitaire Mustapha, 1 place du 1er Mai,
Algiers 16000, Algeria.
(4)Service de Neurologie B, Hôpital Gui de Chauliac, 34295 Montpelliers cedex 5,
(5)Laboratoire de Biochimie et Génétique Moléculaire, CHU Limoges, France.
(6)Département de Biochimie, Centre de Biologie Est, Hospices Civils de Lyon,
F-69500 Bron, France.
(7)Centre de référence «neuropathies périphériques rares», service et laboratoire de
Neurologie, CHU Limoges, France.
(8)Laboratoire de Biochimie et Génétique Moléculaire, CHU Limoges, France; Centre de
référence «neuropathies périphériques rares», service et laboratoire de
Neurologie, CHU Limoges, France.

Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to
pressure palsies (HNPP) are both autosomal-dominant disorders linked to
peripheral myelin anomalies. CMT1A is associated with a Peripheral Myelin Protein
22 (PMP22) duplication, whereas HNPP is due to a PMP22 deletion on chromosome 17.
In spite of this crucial difference, we report three observations of patients
with the 1.4 megabase CMT1A duplication and atypical presentation
(electrophysiological, clinical or pathological): a 10 year-old girl with
tomaculous lesions on nerve biopsy; a 26 year-old woman with recurrent
paresthesiae and block conduction on the electrophysiological study; a 46
year-old woman with transient recurrent nerve palsies mimicking HNPP. These
observations highlight the wide spectrum of CMT1A and the overlap between CMT1A
and HNPP (both linked to the PMP22 gene), and finally illustrate the complexity
of the genotype-phenotype correlations in Charcot-Marie-Tooth diseases.

Copyright © 2014 Elsevier B.V. All rights reserved.

PMID: 24792522 [PubMed – in process]

Curiouser and Curiouser….


Study: Optic and auditory pathway dysfunction in demyelinating neuropathies.


Acta Neurol Scand. 2014 Feb 20. doi: 10.1111/ane.12226. [Epub ahead of print]

Optic and auditory pathway dysfunction in demyelinating neuropathies.



The involvement of optic and auditory pathways has rarely been studied in demyelinating polyneuropathies. We here aimed to study this further in a cohort of patients with acquired and gentic demyelinating neuropathy.


We studied eight patients with hereditary neuropathy with liability to pressure palsies (HNPP), six with Charcot-Marie-Tooth disease type 1A (CMT1A), ten with chronic inflammatory demyelinating polyneuropathy (CIDP) and seven with antimyelin-associated glycoprotein (MAG) neuropathy using visual evoked potentials and brainstem auditory evoked potentials.


Optic pathway dysfunction was detected in 6/7 anti-MAG neuropathy patients, about half of those with CIDP and HNPP, but only in 1/6 patients with CMT1A. Peripheral auditory nerve dysfunction appeared common in all groups except HNPP. Brainstem involvement was exceptional in all groups.


We conclude optic nerve involvement may be frequent in all demyelinating polyneuropathies, particularly anti-MAG neuropathy, except in CMT1A. Peripheral auditory nerves may be spared in HNPP possibly due to absence of local compression. Evidence for central brainstem pathology appeared infrequent in all four studied neuropathies. This study suggests that acquired and genetic demyelinating polyneuropathies may be associated with optic and auditory nerve involvement, which may contribute to neurological disability, and require greater awareness. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


BAEP , CIDP , HNPP , VEP , CMT1A, anti-MAG, auditory, cranial, neuropathy, optic


 24571608 [PubMed – as supplied by publisher]

A curious Study, which once again poses more questions than it answers, but that maybe due to only the abstract being available.

Curious in several ways.

The testing methods used, brainstem evoked responses, are generally used to find CNS abnormalities, although it has to be said that they can also show abnormalities along the peripheral portions of the cranial nerves. The optic nerve , one of the cranial nerves which are generally thought to be part of the peripheral nervous system, is thought to be one of the exceptions to this rule. Along with the olfactory nerve it is considered a central nervous system tract rather than a peripheral nerve.

This study appears to suggest that HNPP can show optic nerve dysfunction, but this is not found so readily in cases of CMT1a. A result which would tally with the experience of some members of the HNPP support groups. However, it then goes on to say that the peripheral portion of the auditory nerve tested by Brainstem evoked potentials, is not affected in HNPP but is so in CMT1a. The suggestion being that HNPP is spared because the auditory nerve is not subject to compression.

So why then is the optic nerve not spared? And Compression is but one way in which peripheral nerves can be ‘traumatised’, nerve injury can also be caused by torsion, traction and by infection. Besides one form of compression that can occur in cranial nerves is compression by vascular loops. This is known to happen in auditory, trigeminal and facial nerves, if not other cranial nerves too.

There are also several questions regarding testing and methods used. ie was peripheral end organ testing performed for the auditory nerve, the abstract appears to suggest that it was not.

This study appears to contradict a previous study on sensori-neural hearing loss (SNHL) in cases of PMP22 type HMSN, http://www.ncbi.nlm.nih.gov/pubmed/15891642  , which appeared to show that SNHL was common in CMT1a and perhaps more so in HNPP. It was suggested that HNPP may be more susceptible due to it’s reactivity to extrinsic factors.

This is all very good though, even though it appears to be a contradiction of a previous study. The finding and results cannot be compared without also comparing methods, exclusion criteria, and analysis techniques. This is science, and nothing is written in stone, but there is a stepwise refinement of observation, hypothesis, theory,  and conclusion. It’s an ongoing cyclic process. The two studies are very different, so it should not be surprising that the results will differ.

This study would appear to raise questions of CNS involvement in HNPP, due to the optic nerve dysfunction found during testing. And although auditory nerve dysfunction wasn’t found, this appeared to focus on Brainstem testing of the peripheral portion of the auditory nerve, and yet other peripheral end organ tests did not appear to be carried out, ie pure tone hearing tests.

Vestibular Disorders: Many Varied Causes, and link to CMT

I don’t log onto facebook that often, and when I do it’s often to see if anyone has any new info on the VHT special 6 ultra guitar amp, but as I sprinted on down the virtual corridor I noticed this message posted on some wall or other.

A link to an article on Vestibular Disorders website, Understanding vertigo, and what to do if you have it.

It’s a short article which was originally posted in the Washington Times, and is written by Dr. Tim Hain.

Dr. Hain has a website with possibly the most comprehensive information on vestibular disorders anywhere on the net. He has an impressive CV which includes neurology, otoneurology, otolaryngology and many other disciplines of medicine and science.

Dizziness And Balance Website

I know it’s not specifically to do with HNPP, but Vertigo is something that I have to endure, and have done so for the past 33 years (and possibly more). In my case it’s an inner ear disease of some kind, which has knocked out my vestibular sense and much of my hearing. Both ears are affected, left greater than right. The cause is probably a mix of disease of peripheral end organ, cochlea and vestibular labyrinth, and disease of the auditory and vestibular nerves.


Although there are only tenuous links between HNPP and vestibular nerve involvement, which is very much disputed by some neurologists (not all), there is the problem with balance which is often noted in cases of hereditary sensory motor neuropathy. This is often attrributed to poor proprioception, ie the spatial sense of where the body, or in the case of CMT and HNPP, where the feet are. It is often assumed that the feet are the main cause of proprioceptive loss in CMT / HNPP, but there are many other important proprioceptive areas in the body. The neck, lower back and spine as well as arms. If the neuropathy affects these then balance and potentially dizziness can become a problem.

Further info on Vestibular Disorders and Causes at VEDA, including info on proprioception

Whether or not HNPP or CMT can affect the vestibular sense, is frequently ignored as it is often assumed that the main issue is proprioception. A few studies looking into this have recently been instigated by CMT specialists in the last few years. So that’s a good step forward.

A quick search now reveals that one study has indeed been completed and published, (link in title)

Vestibular impairment in patients with Charcot-Marie-tooth disease.

PMID: 23658384 [PubMed – indexed for MEDLINE]

1. Neurology. 2013 Jun 4;80(23):2099-105. doi: 10.1212/WNL.0b013e318295d72a. Epub
2013 May 8.

Vestibular impairment in patients with Charcot-Marie-tooth disease.

Poretti A(1), Palla A, Tarnutzer AA, Petersen JA, Weber KP, Straumann D, Jung HH.

Author information:
(1)Departments of Neurology, University Hospital Zurich, Switzerland.

OBJECTIVE: This case-control study aimed to determine whether the imbalance in
Charcot-Marie-tooth (CMT) disease is caused only by reduced proprioceptive input
or whether the involvement of the vestibular nerve is an additional factor.
METHODS: Fifteen patients with CMT disease (aged 48 ± 17 years; 8 women)
underwent cervical vestibular-evoked myogenic potentials, which reflect
otolith-spinal reflex function, and quantitative horizontal search-coil
head-impulse testing, which assesses the high-acceleration vestibulo-ocular
reflex of the semicircular canals.
RESULTS: Relative to healthy age-matched control subjects, cervical
vestibular-evoked myogenic potentials were found to be impaired in 75% of
patients (average p13 latency: 23.0 ± 2.7 milliseconds, p = 0.01; average n23
latency: 29.0 ± 1.8 milliseconds, p = 0.01) and the quantitative head-impulse
test in 60% of patients (average gain ± 1 SD: 0.67 ± 0.24, p < 0.001). All
patients with head-impulse test impairment also showed cervical vestibular-evoked
myogenic potential abnormalities, while the reverse was not true.
CONCLUSIONS: We conclude that the neuropathic process in patients with CMT
disease frequently involves the vestibular nerve and that cervical
vestibular-evoked myogenic potentials may be more sensitive than quantitative
head-impulse testing for detecting vestibular involvement, in particular at an
early disease stage.




No mention of HNPP, but I think results would be similar for some, but there might be greater variation due to HNPP’s episodic and environmentally influenced nature.


Orphanet study/review of PMP22 mediated Neuropathies

Orphanet provides information on Rare diseases, or as their tag line tells us

The portal for rare diseases and orphan drugs: “There is no disease so rare that it does not deserve attention”

The last part is in quotes, so I guess someone must have said this at sometime.

They are supporters of the ‘Rare Disease Day‘ events which take place worldwide on the last day of February each year.

One of their aims is to promote research into ‘orphan’ drugs, ie drugs which having been developed and tested have not been found to be ‘economically viable’, because there is only a very small market for these drugs. They may have been developed during research for other more ‘mainstream’ diseases but other drugs were selected in their place. Some of these medications show much promise in treatment of various rare diseases, but without being spotlighted by Orphanet (and other agencies) they would become obsolete.

Orphanet have some brief information about HNPP, it is short fairly concise, but does not go into a great deal of detail about the signs and symptoms that it mentions. Neither are there any references for the studies that first described these signs and symptoms.


There is also the Orphanet Journal of Rare Diseases

This has an in depth article on all diseases caused by mutations of PMP22, (the title below is also a link to the original article)

PMP22 related neuropathies: Charcot-Marie-Tooth disease type 1A and Hereditary Neuropathy with liability to Pressure Palsies

Covering both CMT1a  and HNPP it is based on a review of the literature/studies from the first reported studies on CMT by messrs. Charcot, Marie and Tooth, to present day studies particularly from the past 20-25 years since the molecular basis of the diseases have been known.

189 references in total, so that should keep any researcher busy for quite some time. The Lion’s share are on CMT1a, but over 40 are included for HNPP, and several for the rare types of PMP22 mutation whose phenotypes are either HNPP or CMT1a or a mixture of both.

I haven’t read the article in depth, just a bit of skip and speed reading,  mostly it is a good review, but prattles on about clinical presentation of painless palsy.

Just as a side note about clinical presentation of painless palsy. I don’t believe this means the condition as a whole is painless, this is just Doctor speak for what they see in the clinic at that particular moment in time. It is a snapshot, and is based on what they see and can clinically assess. Mostly they are not interested in what the patient has to say when they are making their clinical judgement. Although that does not excuse them for not listening before or after they have performed their examination. This study also goes on to mention, muscle cramps, paraesthesias and exercise induced myalgia. It could have also mentioned joint pain associated with recurrent palsy but failed to do so. So in summary, in my view, HNPP may well present with a ‘clinical’ painless palsy, but that does not mean or should not be taken to mean that HNPP as a whole is painless.

Below is my summary of the article.

focal motor and sensory peripheral neuropathy
common sites,  median, radial, with ulnar,  peroneal, the most common,
Brachial plexopathy – Erb’s paresis.
axonal thinning at sites of tomacula,
changes at nodes of ranvier,
conduction block ,
Cranial nerve involvement in some cases, ie  trigeminal, hypoglossal, facial nerve, auditory nerve involvement.
CNS involvement in some patients has been found, but this requires further study.

A further summary of the HNPP section follows (my annotations in brackets)

Direct link to HNPP section



Gives a brief description of genetic causes, ie PMP22 deletion on chromosome 17, autosomal dominant ie (50 % chance of inheritance both sexes)

Episodic, Multifocal neuropathy.

Typical presentation, recurrent, transient pressure palsies without pain (pain is more common than these studies would have people believe), focal motor and sensory symptoms in territory of nerves involved.


Prevalence is not well known, figures  vary from 7.3 per 100,000 to 16 per 100,000.

( In 2001, I was told the prevalence was approximately 2-3 per 100,000. Others have been told various other figures, but 2-5 per 100,000 is the most common statistic given.)

Clinical Description.

Episodic, recurrent, transient palsies. Causing numbness, muscular weakness and atrophy. Episodes can be preceded by many minor compressions of a nerve. Common sites (in high to low order),  ulnar, peroneal, brachial, median, radial

Age of onset 2nd to 3rd decade common, but reports exist from birth (Erb’s palsy) to eighth decade.

(My first symptoms were relatively minor, but occurred at around the age of 7 or 8 whilst cutting material with scissors, and losing sensation in the thumb and finger)

The article claims that most patients, 60- 70 %, present with a single focal acute neuropathy ( which may be true but is again only a snapshot, and follow ups over a long period do not yet exist or only in small numbers, a point mentioned in the Prognosis section)

Cranial nerve involvement in some cases, ie  trigeminal, hypoglossal, facial nerve, auditory nerve involvement.

Other uncommon features, short-term positional sensory symptoms, chronic sensory polyneuropathy, chronic sensorimotor polyneuropathy, and subacute peripheral quadriparetic episodes.

Clinical examination can reveal, muscle weakness, atrophy, sensory signs of involvement, reduced or absent tendon reflexes, Pes Cavus (high arches) is common.

The article claims 50% full recovery of an individual palsy. Chronic, long lasting, residual weakness occurs in 10 – 15%

Chronic symptoms include, cramps,  paresthesias and exercise-induced myalgia…. (isn’t this generally referred to as pain, does not matter a jot if it’s secondary, primary or any other -ary, HNPP can be painful,)

Large clinical variability, asymptomatic patients estimated at 6 – 23 %. At the other extreme chronic deficits may mimic a CMT phenotype (albeit with further acute episodes of palsy).


(Nerve conduction tests)

eveyone diagnosed with HNPP, whether symptomatic or not will show, increased distal latencies, focal motor slowing at entrapment sites  but can be near to normal at other sites. Sensory nerve velocities are decreased, along with sensory nevre action potentials.

Nerve Biopsy shows, segmental demyelination with some large fibre loss. A pathological hallmark of Tomacula described as “massive redundancies or overfolding of layers of variable thickness in the myelin sheath”


(What causes the disease)

85%-90% have the common 1.5 mb pair deletion on chromosome 17p11.2 which causes the complete deletion of the PMP22 gene on that chromosome. Some rarer cases involving smaller deletions exist, but all result in  deletion of PMP22 or mutation of PMP22.

Gene dosage hypothesis is supported by findings of low PMP22 protein and low PMP22 mRNA , the levels correspond with phenotype severity.

Focal symptoms caused by reversible conduction block. Structural changes at nodes of Ranvier explain changes in axonal excitability, and lead to conduction block due to pressure or stretch.

(As far as I recall, a Node of Ranvier is a small gap between segments of myelin along the axon. It has the effect of helping to speed up the nerve impulse, through the ability of the impulse to ‘skip’ or jump across the gaps by ‘saltatory’ action. I am not sure how HNPP affects these nodes, but my guess would be that they elongate due to demyelination and tomacula formation which causes the ‘skipping’ to stall… )

Axonal constrictions within tomacula, increasing resistance to action potential propagation, making nerve prone to conduction block. When compressed may causes further axonal thinning.

(I’ve not heard of this before, but if thinning continues through repeated compression is it possible that the axon would eventually be ‘pinched-off’ leading to distal trophic changes and axonal loss. Brings to mind the ‘fulminant presentation during military service’ study)


Clinical signs and symptoms of acute, recurrent peripheral nerve palsies, but also less common manifestations, ie cranial nerve, pain – parethesias, a family history with autosomal dominant pattern is often noted, but not always found. Some posibility of de novo (new mutation) can exist.

Electrophysiology helps with diagnosis, and more recently sonography (ultrasound) has been used to show enlargement of nerves at typical entrapment sites.

If suspected, DNA testing can be performed for the deletion of PMP22, and if negative, further sequencing of the PMP22 gene for possible and rarer mutations.

Nerve Biopsy has been largely superceded.

Differential Diagnosis

Acquired compressive neuropathy, such as carpal tunnel syndrome. But it has been noted in one study that of 50 patients with carpal tunnel syndrome, none were positive for HNPP. HNPP will normally present with recurrence, and often with multiple palsies, and family history.

Mononeuropathies (unrelated to HNPP) can be caused by tumour, bleeding or abscess.

HNA  (hereditary neuralgic amyotrophy) is mentioned as it causes brachial plexopathy. It is said that in HNA it causes pain whereas HNPP it doesn’t. (not in my experience it doesn’t. I have a long standing shoulder injury caused by going over the handlebars (age 16), which caused an Erb’s palsy, I had a dead arm for months, forced movement was extremely painful. It has become a problem in latter years, with chronic variable left arm weakness and intense shoulder, upper arm and neck pain, it needs to be reviewed and assessed, but mostly my neurologists have ignored my requests to do so, due to their ascertainment bias which is reinforced by statements such as the above, ie that HNPP only causes painless palsy.)

Genetic counselling and antenatal diagnosis

Refers reader to CMT section on Genetic counselling. Briefly, autosomal dominant, 50% chance of inheritance both for males and females. Talks about a concensus of not carrying out predictive testing on children to prevent psychological harm, and briefly about pre-implantation testing, pregnancy testing not being frequently requested. (Not sure about this, I’ve heard of quite a few people having requested such testing, but generally it has been refused, or reluctantly performed.)

Management including treatment

Treatment is symptomatic, bracing for palsies either temporarily or if residual weakness occurs permanently.

Avoid activities with risk factors for palsy, ie sitting crossed legged, repetitive activity in hands, leaning on elbows, rapid weight loss.

Avoid Toxins or medications known to cause worsening of neuropathy, vincristine is of particular note.

Studies on surgical decompression of nerves have not been completed, and generally surgery is not considered favourable.


No natural history studies exist. Prognosis unsure.  A study for electrophysiological tests with aging show increased impairment with age at sites of common entrapment, but not correlated with symptoms.

Recovery for acute palsy is often complete, but residual chronic symptoms (and presumably signs) can remain. These can, over time, resemble a CMT phenotype.

” Symptomatic individuals have the frustration and disability associated with recurrent pressure palsies”

Does not affect life expectancy.

PMP22 Mutations

The article has a small section about PMP22 mutations, missense, non-sense, frameshift, and splice-site mutations are discussed. Phenotype is variable, from asymptomatic to severe, from CMT1a to HNPP to phenotypes having complex symptoms characteristic of both phenotypes.

Some discussion of where these mutations fit within the CMT/HMSN classification.


End of Summary…. Please read the full article. Many references are included, that should satisfy the most devoted of researchers.


CMTNEWS Archives

For many years Linda Crabtree’s CMTNEWS was the prime site for information about CMT, and even included some information on HNPP which was written by Maureen Horton who went on to create the HNPP.org website.

There’s a fantastic amount of info on CMTNEWS, lots of really useful suggestions, medical writeups and much much more.

The original site has closed but Linda Crabtree maintains the archive. As with all things internet, sometimes the URL changes slightly, leaving broken links. I’ve now repaired the broken link on this blog to the CMTNEWS section on Fatigue. It’s a really good read

CMTNEWS – Fatigue – http://www.lindacrabtree.com/cmt/fatigue/index.html

CMTNEWS ARCHIVE – http://www.lindacrabtree.com/cmt/


HNPP, CMT1 A&C and the LITAF Gene

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,

Clinical, electrophysiological and molecular findings in early onset hereditary neuropathy with liability to pressure palsy.


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.


Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth disease 1C

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.

PMID: 12525712

Also it has been noted that some mutations in the LITAF gene are known to cause a compound form of CMT with early onset in people with confirmed PMP22 duplication

Early onset neuropathy in a compound form of Charcot-Marie-Tooth disease.


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.

PMID: 15786462


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.


Further Information On CMT1C