Autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths (CMT4B).
Hereditary motor and sensory neuropathy with focally folded myelin sheaths, or Charcot-Marie-Tooth neuropathy type 4B (CMT4B), is a distinct clinical and genetic entity belonging to the heterogeneous group of autosomal recessive demyelinating neuropathies. We first described a large inbred pedigree with 10 patients affected by CMT4B, which enabled us to uncover the genetic findings, clinical spectrum, and natural history of such a disorder. The clinical picture was characterized by infantile onset with progressive symmetric distal and proximal muscular weakness. Using homozygosity mapping and haplotype sharing analysis, we found evidence of linkage of chromosome 11q23. We then identified a second unrelated family in which two individuals were affected with CMT4B. Although the clinical findings were similar to those previously reported, we excluded the disease locus segregating in this smaller pedigree from the 11q23 region. We thus provided evidence for a second locus causing the CMT4B phenotype. All these findings indicate that CMT4B seems to be phenotypically quite homogeneous, but is genetically heterogeneous.