198 co-enzyme Q have not been proven effective in treating CMT. Aerobic exercise and rehabilitation play an essential role in preserving quality of life of patients with CMT. A small percentage of patients with inherited neuropathy may respond to immunomodulatory therapy, such as prednisone or intravenous gammaglobulin (IVIG). Potentially neuro- toxic medications, such as vincristine or cisplatinum, should be avoided [18]. Experimental studies showed that proges- terone antagonist improves neuropathy in CMT1A rats, and it represents a promising pharmacologic target for CMT1A patients [19, 20]. Dejerine–Sottas neuropathy and congenital hypomyelinating neuropathy Dejerine–Sottas (DSN) and congenital hypomyelinating (CHN) neuropathies are rare, severe, infantile-onset, demyelinating peripheral nerve diseases. DSN is transmitted as an autosomal dominant or recessive trait (Table 1). Clinical onset occurs at up to 2 years of age, with motor and sensory impairment and skeletal deformities, more frequently represented by sco- liosis. NCV of DSN patients is greatly compromised, with values \15 m/s. Sural nerve biopsies could show marked demyelination or predominant axonal loss [8, 18]. CHN, an autosomal dominant or recessive disease (Table 1), is characterized by severe hypotonia (‘‘ﬂoppy infant’’), dysphagia, and respiratory insufﬁciency, usually occurring within the ﬁrst year of life. NCV is very slow (\10 m/s), and sural nerve biopsy presents pathological features similar to those of DSN [16, 17]. Hereditary neuropathy with liability to pressure palsies The prevalence of hereditary neuropathy with liability to pressure palsies (HNPP) is estimated to be at least 16 per 100,000 [21]. HNPP is an autosomal dominant disorder due to a deletion in chromosome 17p11.2 which codes for periph- eral myelin protein (PMP22), an integral membrane protein that is a major component of myelin in the peripheral nervous system [22]. Patients present acute and transient episodes of focal neuropathies, commonly affecting the ulnar, radial, and peroneal nerves and the brachial plexus. These episodes are typically painless, recurrent, and occur after trauma or pressure, or with no evident precipitating factor [23]. The palsies may be debilitating, last for days to weeks, and require installation of speciﬁc orthosis. Onset of HNPP is usually in adolescence, with a high degree of penetrance; however, clinically asymptomatic gene carriers are repor- ted. Neurological examination could evidence hypoactive 123 J Orthopaed Traumatol (2010) 11:195–201 deep tendon reﬂexes and mild pes cavus, even in clinically asymptomatic patients [24]. With ageing, these patients can have a signiﬁcant clin- ical overlap with CMT1, as the repeated injuries to the nerve can prevent full reversal. Electrophysiological examination shows prolonged motor and sensory nerve conduction velocities (NCV) [25] and conduction blocks that are characteristic of the affected nerves, especially over entrapment sites. NCV abnormali- ties are also present in those nerves apparently unaffected by palsy and in asymptomatic gene carriers [26]. Histological analysis of sural nerve biopsies shows segmental area of de- and remyelination. The pathological hallmark of HNPP is presence of tomacula, consisting of massive variable myelin overfolding [27]. In rare of HNPP patients nerve biopsy could be present only the axonal regeneration signs [28]. There is no speciﬁc treatment for HNPP. Current man- agement consists of early detection and diagnosis of the disease, to reduce excessive force or repetitive movements, or to avoid static joint positions. Chemotherapeutic agents, such as vincristine, should be used with great caution [29]. Distal hereditary motor neuropathies Distal hereditary motor neuropathies (dHMNs) are very rare genetic disorders (approximately prevalence rate of 1/100,000) [30], inherited as an autosomal dominant, autosomal recessive or X-linked trait [31–33] (Table 2). dHMN usually presents as a classical peroneal muscular atrophy syndrome without sensory symptoms [34]. The clinical picture consists of progressive weakness and wasting of the extensor muscles of the toes and feet. Later, Table 2 Genetic classiﬁcation neuropathies of distal hereditary motor Type HMN I HMN II HMN II HMN III HMN IV HMN V HMN V HMN VI HMN VIIA HMN VIIB HMN/ALS4 HMN-J Congenital distal SMA Inheritance AD AD AD AR AR AD AD AR AD AD AD AR AD Gene/locus Unknown HSP27 (HSPB1) HSP22 (HSPB8) 11q13 11q13 GARS BSC12 IGHMBP2 2q14 DCTN1 SETX 9p21.1-p12 12q23-12q24 Distal hereditary motor neuropathies (http://www.ncbi.nlm.nih.gov/ omim)