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 Plus which includes sequencing of the genes EGR2, GJB1, MPZ, PMP22 and PRX
  • Dejerine-Sottas syndrome panel NGS Panel Plus + 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 CENTOGENE´s Dejerine-Sottas syndrome panel:

Gene (OMIM)Disease Inheritance Locus

EGR2

(129010)

Dejerine-Sottas disease

Charcot-Marie-Tooth disease, type 1D

Neuropathy, congenital hypomyelinating, 1 
AD, AR 10q21.3

GJB1

(304040)
Charcot-Marie-Tooth neuropathy, X-linked dominant, 1          XLD Xq13.1

MPZ

(159440)

Charcot-Marie-Tooth disease, dominant intermediate D Charcot-Marie-Tooth disease, type 1B   

Charcot-Marie-Tooth disease, type 2I                     

Charcot-Marie-Tooth disease, type 2J                    

Dejerine-Sottas disease                                                

Neuropathy, congenital hypomyelinating            

Roussy-Levy syndrome 
AD, AR 1q23.3

PMP22

(601097)

Charcot-Marie-Tooth disease, type 1A                   

Charcot-Marie-Tooth disease, type 1E                    

Neuropathy, inflammatory demyelinating

Dejerine-Sottas disease

Neuropathy, recurrent, with pressure palsies

Roussy-Levy syndrome 
AD, AR 17p12

PRX

(605725)

Charcot-Marie-Tooth disease, type 4F                    

Dejerine-Sottas disease 
AD, AR 19q13.2