Classification of neuropathies into Charcot-Marie-Tooth syndrome (CMT, hereditary motor and sensory neuropathy) or purely motor neuropathies is relatively easy in single patients but subtle sensory findings can vary in different affected individuals in a family. We examined the extent of sensory involvement in different individuals in two new X-linked neuropathy syndromes (CMTX3 and dSMAX) and in some dominantly inherited mainly motor neuropathies. CMTX3 is a mild X- linked recessive CMT phenotype linked to Xq26-28. dSMAX (distal spinal muscular atrophy linked to Xq13-21). We describe a new family linked to this locus that has some sensory findings which could also be described as a motor and sensory neuropathy i.e. a form of CMT.
In our dominant distal hereditary motor neuropathy (HMN) family linked to chromosome 7 (dHMN1) we also found some affected individuals with sensory signs as well as reduced sensory action potentials. In reported HMN families with known mutations in GARS, SETX, HSPB1 and HSPB8 genes and in many of our HMN families with unknown gene mutations, there is sensory involvement producing a CMT phenotype in some individuals. These disorders do not easily fit into traditional hereditary neuropathy classifications and should be recognised as CMT/HMN overlap syndromes. Recognition of overlap syndromes may assist development of more accurate gene screening paradigms.
Hereditary neuropathy Sensory signs CMT dSMAX Motor neuropathy
This is a preview of subscription content, log in to check access.
Auer-Grumbach M, Schlotter-Weigel B, et al. (2005). Phenotypes of the N88S Berardinelli-Seip congenital lipodystrophy 2 mutation. Ann Neurol 57(3): 415–424.CrossRefPubMedGoogle Scholar
Casasnovas C, Banchs I, et al. (2006). Clinical and molecular analysis of X-linked Charcot-Marie-Tooth disease type 1 in Spanish population. Clin Genet 70(6): 516–523.CrossRefPubMedGoogle Scholar
Dierick I, Baets J, et al. (2008). Relative contribution of mutations in genes for autosomal dominant distal hereditary motor neuropathies: a genotype-phenotype correlation study. Brain 131(Pt 5): 1217–1227.PubMedGoogle Scholar
Dierick I, Irobi J, et al. (2007). Genetic variant in the HSPB1 promoter region impairs the HSP27 stress response. Hum Mutat 28(8): 830.CrossRefPubMedGoogle Scholar
Houlden H, Laura M, et al. (2008). Mutations in the HSP27 (HSPB1) gene cause dominant, recessive, and sporadic distal HMN/CMT type 2. Neurology 71(21): 1660–8.Google Scholar
Ionasescu VV, Trofatter J, et al. (1991). Heterogeneity in X-linked recessive Charcot-Marie-Tooth neuropathy. Am J Hum Genet 48(6): 1075–1083.PubMedGoogle Scholar
Irobi J, Van den Bergh P, et al. (2004). The phenotype of motor neuropathies associated with BSCL2 mutations is broader than Silver syndrome and distal HMN type V. Brain 127(Pt 9): 2124–2130.CrossRefPubMedGoogle Scholar
Kennerson M, Nicholson G, et al. (2009). X-linked distal hereditary motor neuropathy maps to the DSMAX locus on chromosome Xq13.1-q21. Neurology 72(3): 246–52.Google Scholar
Muglia M, Magariello A, et al. (2008). A novel locus for dHMN with pyramidal features maps to chromosome 4q34.3-q35.2. Clin Genet 73(5): 486–491.CrossRefPubMedGoogle Scholar
Myrianthopoulos NC, Lane MH, et al. (1964). Nerve Conduction and Other Studies in Families with Charcot-Marie-Tooth Disease. Brain 87: 589–608.CrossRefPubMedGoogle Scholar
Rohkamm B, Reilly MM, et al. (2007). Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome. J Neurol Sci 263(1–2): 100–106.CrossRefPubMedGoogle Scholar
Takata RI, Speck Martins CE, et al. (2004). A new locus for recessive distal spinal muscular atrophy at Xq13.1-q21. J Med Genet 41(3): 224–229.CrossRefPubMedGoogle Scholar
Tang B, Liu X, et al. (2005). Mutation analysis of the small heat shock protein 27 gene in chinese patients with Charcot-Marie-Tooth disease. Arch Neurol 62(8): 1201–1207.CrossRefPubMedGoogle Scholar
Vucic S, Kennerson M, et al. (2003). CMT with pyramidal features. Charcot-Marie-Tooth. Neurology 60(4): 696–699.PubMedGoogle Scholar
Windpassinger C, Auer-Grumbach M, et al. (2004). Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome. Nat Genet 36(3): 271–276.CrossRefPubMedGoogle Scholar
Zhu D, Kennerson ML, et al. (2005). Charcot-Marie-Tooth with pyramidal signs is genetically heterogeneous: families with and without MFN2 mutations. Neurology 65(3): 496–497.CrossRefPubMedGoogle Scholar