Dejerine–Sottas disease and hereditary demyelinating polyneuropathy of infancy

Abstract

Dejerine-Sottas disease (DSD) was originally described as a hypertrophic polyneuropathy characterized by onset in infancy or early childhood in patients born to unaffected parents. The clinical features included distal sensory changes with ataxia; pes cavus, at times with kyphoscoliosis; motor deficit and atrophy predominating in the distal lower limbs and progressing toward the proximal limbs following a length-dependent pattern; palpable nerve hypertrophy; and Argyll-Robertson pupils. The morphological hallmark was the extensive nerve and root hypertrophy associated with demyelination-remyelination of surviving, originally myelinated axons and profuse Schwann-cell proliferation forming onion bulbs. Wide variations in clinical manifestations of chronic demyelinating polyneuropathies of early onset in children born to unaffected parents have now been reported, with only some of the characteristics required in the original study, and at least seven genes encoding the myelin proteins P0, PMP22, the transcriptional factor EGR2, and others have been implicated. Thus, DSD is now a component of the hereditary demyelinating polyneuropathies of infancy that also include subsets of the recently individualized CMT4 neuropathies. The presumed recessive transmission of patients with DSD should be confirmed by molecular genetic analysis, which is still negative in a significant proportion of patients. The nerve biopsy can be useful in patients in whom genealogical or DNA abnormalities in favor of a genetic disorder are missing, because in a few patients with a progressive or relapsing course the diagnosis of early-onset chronic inflammatory demyelinating polyneuropathy must be considered.

Compound heterozygous deletions of PMP22 causing severe Charcot‐Marie‐Tooth disease of the Dejerine‐Sottas disease phenotype

“…However, the proband's compound heterozygosity resulted in a very severe clinical phenotype. The early, severe, diffuse, progressive, multifocal neuropathies with marked slowing of NCV, along with the elevated CSF protein and abundant ''onion bulb'' formation on nerve biopsies, are all consistent with the diagnosis of DSD [Dyck and Lambert, 1968;Plante-Bordeneuve and Said, 2002].…”

“…The majority of patients are diagnosed by the age of 2 years. Affected nerves show the typical ''onion bulb'' formation seen with CMT [Dyck and Lambert, 1968;Plante-Bordeneuve and Said, 2002]. Although classically DSD is inherited in an autosomal recessive manner, autosomal dominant inheritance has also been described [Roa et al, 1993;Nelis et al, 1999].…”

Genetic spectrum of hereditary neuropathies with onset in the first year of life

“…Hereditary motor and sensory neuropathies with onset in infancy are rare disorders that were first described by Dejerine and Sottas, 1893 in the late 19th century as a separate disease, distinct from the more commonly occurring Charcot–Marie–Tooth neuropathy (Gabreels-Festen, 2002; Plante-Bordeneuve and Said, 2002). Today, we know that these early onset hereditary neuropathies are not a single entity but rather represent a broad clinical and genetic spectrum of disorders that is still incompletely understood (Ryan and Ouvrier, 2005).…”

Charcot–Marie–Tooth diseases: an update and some new proposals for the classification

“…A few years afterwards, Jules Dejerine and Jules Sottas described the ‘hypertrophic interstitial neuritis’ (now called Dejerine–Sottas syndrome),13 which corresponds to a hereditary motor and sensory neuropathy (HMSN) characterised by onset in infancy or early childhood. Later on, Gustave Roussy and Gabriel Levy14 described another variant of HMSN with tremor and ataxia, called ‘Roussy–Levy syndrome’ (RLS),15 now considered as a variant of CMT1 (the demyelinating form of CMT),16 further increasing the nosologic complexity of CMT 17. In 1927, Sergeij Dawidenkov presented a clinical classification in which these hereditary neuropathies were classified into 12 categories,18 but it has never been routinely used.…”