200 the disease, when other signs of HPN may not yet be present or evident. When should HPN be suspected in a patient with pes cavus? Clinical data suggestive of HPN are represented by evidence of: bilateral pes cavus, positive family history for pes cavus and/or gait impairment, distal muscle hypotrophy of limbs, and sensorial and/or motor dysfunction. When one or more of these signs are present, the patient should be subjected to neurological evaluation to complete the HPN diagnostic algorithm, based on electroneurograph- ysiological studies and, subsequently, molecular analysis (see Fig. 3). Conﬂict of interest None. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which per- mits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. References 1. Japas LM (1968) Surgical treatment of pes cavus by tarsal v- osteotomy: preliminary report. J Bone Joint Surg Am 50:927–944 2. Brewerton DA, Sandifer PH, Sweetnam DR (1963) Idiopathic pes cavus: an investigation into its aetiology. Br Med J 14:659–661 3. Pareyson D, Marchesi C (2009) Diagnosis, natural history, and management of Charco-Marie-Tooth disease. Lancet Neurol 8:654–667 4. Irobi J, Dierick I, Jordanova A, Claeys KG, De Jonghe P, Timmerman V (2006) Unraveling the genetics of distal hereditary motor neuronopathies. Neuromolecular Med 8:131–146 5. Martyn CN, Hughes RAC (1997) Epidemiology of peripheral neuropathy. J Neurol Neurosurg Psychiatry 62:310–318 6. Boerkoel CF, Takashima H, Lupski JR (2002) The genetic con- vergence of Charcot-Marie-Tooth disease types 1 and 2 and the role of genetics in sporadic neuropathy. Curr Neurol Neurosci Rep 2:70–77 7. Pareyson D, Testa D, Morbin M, Erbetta A, Ciano C, Lauria G, Milani M, Taroni F (2003) Does CMT1A homozygosity cause more severe disease with root hypertrophy and higher CSF pro- teins? Neurology 60:1721–1722 8. Chance PF, Lupski JR (1994) Inherited neuropathies: Charcot Marie Tooth disease and related disorders. Baillieres Clin Neurol 3:373–385 9. Shy ME, Jani A, Krajewski K, Grandis M, Lewis RA, Li J, Shy RR, Balsamo J, Lilien J, Garbern JY, Kamholz J (2004) Pheno- typic clustering in MPZ mutations. Brain 127:371–384 10. Holmes JR, Hansen ST (1993) Foot and ankle manifestations of Charcot Marie Tooth disease. Foot Ankle 14:476–486 11. Banchs I, Casasnovas C, Albert´ı A, De Jorge L, Povedano M, Montero J, Mart´ınez-Matos JA, Volpini V (2009) Diagnosis of Charcot-Marie-Tooth disease. J Biomed Biotechnol 2009:985415 12. Shy ME, Lupski JR, Chance PF, Klein CJ, Dyck PJ (2005) Hereditary motor and sensory neuropathies: an overview of clinical, genetic, electrophysiologic, and pathologic features. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, pp 1623–1658 123 J Orthopaed Traumatol (2010) 11:195–201 13. Szigeti K, Lupski JR (2009) Charcot-Marie-Tooth disease. Eur J Hum Genet 17:703–710 14. Mann RA, Missirian J (1988) Pathophysiology of Charcot Marie Tooth disease. Clin Orthop 234:221–228 15. Harding AE, Thomas PK (1980) The clinical features of hered- itary motor and sensory neuropathy (types I and II). Brain 103:259–280 16. Birouk N, LeGuern E, Maisonobe T, Rouger H, Gouider R, Tardieu S, Gugenheim M, Routon MC, Le´ger JM, Agid Y, Brice A, Bouche P (1998) X linked Charcot-Marie-Tooth disease with connexin 32 mutations: clinical and electrophysiologic study. Neurology 50:1074–1082 17. Zu¨chner S, Noureddine M, Kennerson M, Verhoeven K, Claeys K, De Jonghe P, Merory J, Oliveira SA, Speer MC, Stenger JE, Walizada G, Zhu D, Pericak-Vance MA, Nicholson G, Timm- erman V, Vance JM (2005) Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot- Marie-Tooth disease. Nature Genet 37:289–294 18. Grandis M, Shy ME (2005) Current therapy for Charcot-Marie- Tooth disease. Curr Treat Options Neurol 7:23–31 19. Sereda MW, Meyerzu Ho¨rste G, Suter U, Uzma N, Nave KA (2003) Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT1A). Nat Med 9:1533–1537 20. Koenig HL, Schumacher M, Ferzaz B, Thi AN, Ressouches A, Guennoun R, Jung-Testas I, Robel P, Akwa Y, Baulieu EE (1995) Progesterone synthesis and myelin formation by Schwann cells. Science 268:1500–1503 21. Meretoja P, Silander K, Kalimo H, Aula P, Meretoja A, Savo- ntaus ML (1997) Epidemiology of hereditary neuropathy with liability to pressure palsies (HNPP) in south western Finland. Neuromuscul Disord 7:529–532 22. Snipes GJ, Suter U, Welcher AA, Shooter EM (1992) Charac- terization of a novel peripheral nervous system myelin protein (PMP-22/SR13). J Cell Biol 117:225–238 23. Pareyson D, Taroni F (1996) Deletion of the PMP22 gene and hereditary liability to pressure palsies. Curr Opin Neurol 9:348–354 24. Chance PF (1999) Overview of hereditary neuropathy with liability to pressure palsies. Ann N Y Acad Sci 14(883):14–21 25. Earl CJ, Fullerton PM, Wakeﬁeld GS, Schutta HS (1964) Hereditary neuropathy with liability to pressure palsies. Q J Med 33:481–498 26. Mouton P, Tardieu S, Gouider R, Birouk N, Maisonobe T, Dubourg O, Brice A, LeGuern E, Bouche P (1999) Spectrum of clinical and electrophysiological features in HNPP patients with the 17p11.2 deletion. Neurology 52:1440–1446 27. Madrid R, Bradley WG (1975) The pathology of neuropathies with focal thickening of the myelin sheath (tomaculous neurop- athy): studies on the formation of the abnormal myelin sheath. J Neurol Sci 25:415–448 28. Sessa M, Nemni R, Quattrini A, Del Carro U, Wrabetz L, Canal N (1997) Atypical hereditary neuropathy with liability to pressure palsies (HNPP): the value of direct DNA diagnosis. J Med Genet 34:889–892 29. Kalfakis N, Panas M, Karadima G, Floroskuﬁ P, Kokolakis N, Vassilopoulos D (2002) Hereditary neuropathy with liability to pressure palsies emerging during vincristine treatment. Neurol- ogy 59:1470–1471 30. Radhakrishnan K, Thacker AK, Maloo JC (1988) A clinical, epidemiological and genetic study of hereditary motor neuropa- thies in Benghazi, Libya. J Neurol 235:422–424 31. Nelson JN, Amick LD (1966) Heredofamilial progressive spinal muscular atrophy: a clinical and electromyographic study of a kinship. Neurology 16:306