The range of chronic demyelinating neuropathy of infancy: a clinico-pathological and genetic study of 15 unrelated cases

The concept of Dejerine-Sottas disease, which corresponds to presumed reces sive demyelinating neuropathies with onset in infancy, remains controversia l. To learn more on the subject, we performed a clinico-pathological and mo lecular genetic study in 15 unrelated patients with the Dejerine-Sottas phe notype seen over a 16 year period. There were 12 females and 3 males, born to asymptomatic parents. Study of the PMP22, P-0 and Egr2 genes was perform ed in all cases and 14 underwent a nerve biopsy. First manifestations of ne uropathy occurred before 3 years of age in all patients. An inherited disor der was suspected in 10 patients, because of their family history and/or di sclosure of a molecular genetic defect in 4 of them. One patient had a rece ssively transmitted homozygous point mutation (Arg157Trp) of the PMP22 gene . A heterozygous duplication of the 17p11.2-12 segment was detected in one offspring of a consanguineous marriage. One patient carried a "de novo" het erozygous Ser72Leu substitution in the PMP22. A heterozygous double mutatio n of the Po gene including a "de novo"Val42 deletion and an Ala221 Thr subs titution, maternally inherited, were found in an apparently sporadic case. No mutation of the Egr2 gene was identified. A neuropathy with focally fold ed myelin sheaths (CMT4B) was diagnosed in the nerve biopsy specimens of tw o patients. In five patients, the clinico-pathological findings along with the absence of an identified mutation suggested the diagnosis of chronic in flammatory demyelinating polyneuropathy of infantile onset. Our findings il lustrate the genetic heterogeneity of cases with identified mutations, the scarcity of cases with "demonstrated" recessive transmission and the likeli hood of early acquired chronic inflammatory demyelinating polyneuropathy in several patients.