Charcot-Marie-Tooth disease and Atypical Mole Syndrome phenotype

Dr Nikolaos Kostopoulos ( EADO fellow), Dr Heather Shaw, Dr Paul Nathan and  Dr Veronique Bataille

Mount Vernon Cancer Centre, Northwood, UK

Case presentation: A 41 year old male presented to the dermatology department with multiple atypical naevi. He was diagnosed with Charcot Marie Tooth (CMT) in his twenties. He had no personal or family history of melanoma but a very strong family history of lung cancer affecting two maternal aunts and one maternal grandmother. He also has two maternal cousins with CMT. He suffers from diabetes type 2 and is on Metformin. On examination, he has a florid atypical mole syndrome phenotype with multiple junctional and atypical naevi on the torso and limbs. He has muscular atrophy of the calf muscles.

Images 1-2. Atypical naevi on the torso

Images 3-4. Atypical naevi and marked bilateral muscular atrophy of the lower legs

CMT is a neurodegenerative disease with as many as 1 in 2500 people affected (1). There has been more than 80 genes linked to CMT and many subtypes exist with dominant and recessive inheritance (2). Associations have already been made between melanoma and CMT with four previous case reports (3,4). Neural cells and melanocytes both originate from the neural crest and it is likely that shared genetic defects explain the co-existence of melanoma susceptibility and CMT (3,4). On a cellular level, melanocytes and Schwann cells possess common histopathologic and ultrastructural characteristics. Naevus cells morphologically may resemble neural crest-derived Schwann cells (5,6). The PMP22 gene has been linked to CMT and downregulation of the PMP22 gene has been found in BRAF mutated naevi (7,8). A disease susceptibility locus for familial melanoma has been reported on the 1p36 locus and one of the CMT type 2 genes is on chromosome 1, within the 1p35–p36 region (9,10,11,12).

Key Message

There are no previous case reports on the co-existence of the atypical mole syndrome and CMT as seen in our patient but the naevus phenotype was not described in previous publications. With melanocytes and neural cell sharing the same neural cell of origin, melanoma is likely to be found in the context of various neural disorders. Amyotrophic Lateral Sclerosis and Parkinson disease have also been reported in excess in melanoma patients and we suggest that patients with melanoma and/or the atypical mole syndrome and neural disorders should be reported into the Orphanet database ( (13,14).


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  10. Goldstein AM et al., Two-Locus Linkage Analysis of Cutaneous Malignant Melanoma/Dysplastic Nevi Am. J. Hum. Genet. 58:1050-1056, 1996
  11. Ben Othmane K et al., Localization of a gene (CMT2A) for autosomal dominant Charcot-Marie-Tooth disease type 2 to chromosome 1p and evidence of genetic heterogeneity Genomics. 1993 Aug;17(2):370-5
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  14. Albert S. M., Neurodegenerative Disease and Cancer:A Critical Role for Melanoma? Neuroepidemiology 2010;35:305–306

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