Publications about genetic testing for neurological disorders
  1. Dejerine-Sottas Syndrome Panel

Dejerine-Sottas Syndrome Panel

August 30, 2018

Disease summary:

Dejerine-Sottas syndrome (DSS) is a hereditary neuropathy is a severe phenotype of Charcot-Marie-Tooth disease (CMT). It is characterized by early-onset (first 2 years of life), delayed motor development, slow nerve conduction velocity and severe loss of myelinated fibers in nerve biopsy2,3.

DSS is associated with pathogenic variants in the genes associated with myelin formation and/or function: EGR2, GJB1, MPZ, PMP22 and PRX  (Table 1).

Autosomal recessive, autosomal dominant

Major clinical symptoms 1, 2:

  • Severe progressive weakness of the distal muscles in the feet and/or hands
  • Distal sensory loss
  • Difficulties walking, frequent tripping, falls
  • High-arched feet (Pes cavus), weak ankle dorsiflexion, foot drop
  • Poor hand control, difficulties writing
  • Reduced tendon reflexes

Less common symptoms 1, 2:

  • Nystagmus
  • Anisocoria
  • Hearing loss
  • Nerve conduction velocity <12m/s
  • Specific findings on nerve biopsy  (marked reduction in myelinated fiber density, thin myelin sheaths, and onion bulb formations)
  • Identification of pathogenic variant(s) in one of the associated genes (Table 1)

There is actually no cure for Dejerine-Sottas syndrome but numerous symptomatic treatments exist, including1, 4:

  • Special shoes and ankle/foot orthoses for mobility
  • Orthopedic surgery if needed for severe pes cavus
  • Pain-relief medication, carbamazepine or gabapentin for neuropathic pain.
  • Hereditary neuropathy with liability to pressure palsies (HNPP) caused by pathogenic variants in PMP22
  • CMT syndrome with spasticity caused by pathogenic variants in BSCL2, SPART or other genes
  • Refsum disease caused by pathogenic variants in PEX7 or PHYH
  • Metachromatic leukodystrophy caused by pathogenic variants in ARSA
  • Krabbe disease caused by pathogenic variants in GALC
  • Friedreich ataxia caused by pathogenic variants in FXN
  • X-linked disorders with neuropathy (Pelizaeus-Merzbacher disease, Adrenomyeloneuropathy)
  • Diabetes mellitus
  • Thyroid disease
  • Alcoholism
  • Vitamin B12 deficiency

To confirm/establish the diagnosis of Dejerine-Sottas syndrome, CENTOGENE offers the following tests:

  • Dejerine-Sottas syndrome panel NGS Panel which includes sequencing of the genes EGR2, GJB1, MPZ, PMP22 and PRX
  • Dejerine-Sottas syndrome panel NGS Panel + CNV which includes sequencing of the above genes and additionally detection of large deletions and duplications from the NGS data
  • Individuals with a positive family history of Dejerine-Sottas syndrome
  • Individuals with symptoms of Dejerine-Sottas syndrome (regardless of family history)

Confirmation of a clinical diagnosis through genetic testing of Dejerine-Sottas syndrome can allow for genetic counseling and may direct medical management.

Table 1. Overview of the genes in Dejerine-Sottas syndrome panel:

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
EGR2 129010 Dejerine-Sottas syndrom; congenital hypomyelinating neuropathy; type 1D Charcot-Marie-Tooth disease AD, AR 10
GJB1 304040 Charcot-Marie-Tooth disease type 1 XLD 11
MPZ 159440 type 1B Charcot-Marie-Tooth disease; Dejerine-Sottas syndrom; type 2I Charcot-Marie-Tooth disease; type 2J Charcot-Marie-Tooth disease AD, AR 9
PMP22 601097 type 1A Charcot-Marie-Tooth disease; Dejerine-Sottas syndrom; Neuropathy, recurrent, with pressure palsies ?AD, AD, AR 11
PRX 605725 Dejerine-Sottas syndrom; type 4F Charcot-Marie-Tooth disease AD, AR 22