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:
stephane.mathis@chu-poitiers.fr.
(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,
France.
(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….

 

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