M. Mçller
3.3 Electrodiagnostic features and differential
5.4.5 Minifascicular peripheral neuropathy,
z Clinical features: To our knowledge, only one patient with this phenotype has been reported. The patient showed premature female genitalia and a sparsely characterized peripheral neuropathy [47].
z Pathology, genetics and pathomechanism: The sural nerve biopsy demon-strated extensive formation of so called ªminifasciclesº. Minifascicles con-tain several axon-Schwann cell units that are separated by one-to-several layers of flattened cell processes with the morphology of perineurial cells, which are normally found surrounding large nerve fascicles. The possibili-ty of a mutation in the desert hedgehog (DHH) gene was suggested by a similar phenotype of the DHH-deficient mouse [38]. A point mutation in the translation initiation codon of the DHH gene was found in the patient.
A very similar phenotype without a mutation in the coding region of the DHH gene was described recently [45].
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6.1 Autosomal dominant CMT1 and HNPP
6.1.1 Clinical features
Charcot-Marie-Tooth disease type 1 (CMT1), also called hereditary motor and sensory neuropathy type I (HMSN I), shows a classical CMT phenotype with progressive muscular atrophy of the distal muscles, foot deformities (pes cavus and claw toes) and absent deep tendon reflexes [29, 158]. In all cases, a varying degree of symmetrical sensory loss is present. Different types have been designated on the basis of genetic classification, i.e., by locus or by gene.
Therefore, the different CMT1 types do not necessarily reflect different clin-ical phenotypes.
In CMT1A, caused by a 1.4 Mb duplication on chromosome 17p11 or by point mutations in PMP22, the first overt symptoms usually appear in the second decade of life, but careful neurological examination reveals earlier neurologic deficits with a mean age of onset around four years [13]. The course is mild to moderately severe. In some cases, a visible and palpable hypertrophy of peripheral nerves, especially the great auricular nerve, can be found. CMT1A patients with point mutations are usually more severely affected than patients with a CMT1A duplication. Patients homozygous for the CMT1A duplication have a more severe phenotype and an earlier onset age (< 1 year) than the heterozygous CMT1A duplication patients [82]. In a few CMT1A patients, deafness and/or vocal cord dysfunction have been ob-served [20, 67, 129]. CMT1B, caused by point mutations in the MPZ gene, is usually more severe than CMT1A. The age of onset is very variable as well as the expressivity (severity of the disease) in different members of the same CMT1B family [136]. Some CMT1B patients have special features, such as significant sensory signs, early involvement of upper extremities [178], bulbar signs [28], auditory involvement [142], and pupillary abnor-malities [36]. Patients with CMT1C, caused by point mutations in the LI-TAF gene, manifest characteristic CMT symptoms, including high-arched feet, distal muscle weakness and atrophy, depressed deep-tendon reflexes and sensory impairment [12]. Most patients with CMT1D, caused by point