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Dejerine-Sottas disease(CMT3; HMSN3; DSS; DSN)

MedGen UID:
3710
Concept ID:
C0011195
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease type 3; Dejerine-Sottas neuropathy; Hereditary motor and sensory neuropathy 3; HEREDITARY MOTOR AND SENSORY NEUROPATHY TYPE III; HMSN Type III; Hypertrophic neuropathy of Dejerine-Sottas
SNOMED CT: Hypertrophic hereditary neuropathy (111499002); Hereditary motor and sensory neuropathy type III (111499002); Hypertrophic demyelinative neuropathy of infancy (111499002); Déjérine-Sottas disease (111499002); Hereditary sensory-motor neuropathy, type III (111499002); Hereditary hypertrophic neuropathy (111499002); Dejerine-Sottas disease (111499002); Progressive hypertrophic interstitial neuropathy (111499002); Hereditary motor and sensory neuropathy, type III (111499002); HSMN III (111499002); HMSN III (111499002); Charcot-Marie-Tooth disease type 3 (111499002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Genes (locations): EGR2 (10q21.3); MPZ (1q23.3); PMP22 (17p12); PRX (19q13.2)
 
Monarch Initiative: MONDO:0007790
OMIM®: 145900
Orphanet: ORPHA64748

Definition

Dejerine-Sottas neuropathy is a demyelinating peripheral neuropathy with onset in infancy. It can show autosomal dominant or recessive inheritance. Affected individuals have delayed motor development due to severe distal motor and sensory impairment, resulting in difficulties in gait. Some patients have generalized hypotonia in infancy. Other features may include pes cavus, scoliosis, and sensory ataxia. Nerve conduction velocities are severely decreased (sometimes less than 10 m/s), and sural nerve biopsy shows severe loss of myelinated fibers (summary by Baets et al., 2011). [from OMIM]

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Distal lower limb muscle weakness
MedGen UID:
324514
Concept ID:
C1836450
Finding
Reduced strength of the distal musculature of the legs.
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
Split hand
MedGen UID:
397570
Concept ID:
C2699510
Congenital Abnormality
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middle fingers as far as oligo- or monodactyl hands.
Ulnar claw
MedGen UID:
871311
Concept ID:
C4025799
Congenital Abnormality
An abnormal hand position characterized by hyperextension of the fourth and fifth fingers at the metacarpophalangeal joints and flexion of the interphalangeal joints of the same fingers such that they are curled towards the palm.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Sensory ataxia
MedGen UID:
66020
Concept ID:
C0240991
Sign or Symptom
Incoordination of movement caused by a deficit in the sensory nervous system. Sensory ataxia can be distinguished from cerebellar ataxia by asking the patient to close his or her eyes. Persons with cerebellar ataxia show only a minimal worsening of symptoms, whereas persons with sensory ataxia show a marked worsening of symptoms.
Steppage gait
MedGen UID:
98105
Concept ID:
C0427149
Finding
An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Broad-based gait
MedGen UID:
167799
Concept ID:
C0856863
Finding
An abnormal gait pattern in which persons stand and walk with their feet spaced widely apart. This is often a component of cerebellar ataxia.
Peripheral demyelination
MedGen UID:
451074
Concept ID:
C0878575
Pathologic Function
A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
Increased CSF protein concentration
MedGen UID:
329971
Concept ID:
C1806780
Finding
Increased concentration of protein in the cerebrospinal fluid.
Hypertrophic nerve changes
MedGen UID:
322038
Concept ID:
C1832776
Finding
Segmental peripheral demyelination/remyelination
MedGen UID:
335873
Concept ID:
C1843077
Finding
A segmental pattern of demyelination and regeneration (remyelination) affecting peripheral nerves.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Onion bulb formation
MedGen UID:
376237
Concept ID:
C1847906
Finding
Repeated episodes of segmental demyelination and remyelination lead to the accumulation of supernumerary Schwann cells around axons, which is referred to as onion bulb formation. This finding affects peripheral nerves.
Decreased sensory nerve conduction velocity
MedGen UID:
336512
Concept ID:
C1849148
Finding
Reduced speed of conduction of the action potential along a sensory nerve.
Impaired distal vibration sensation
MedGen UID:
381262
Concept ID:
C1853767
Finding
A decrease in the ability to perceive vibration in the distal portions of the limbs.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Decreased number of peripheral myelinated nerve fibers
MedGen UID:
346872
Concept ID:
C1858285
Finding
A loss of myelinated nerve fibers in the peripheral nervous system (in general, this finding can be observed on nerve biopsy).
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Myelin tomacula
MedGen UID:
866559
Concept ID:
C4020904
Disease or Syndrome
The presence of multiple sausage-shaped swellings of the myelin sheath (The Latin tomaculum means sausage).
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Tongue fasciculations
MedGen UID:
65987
Concept ID:
C0239548
Finding
Fasciculations or fibrillation affecting the tongue muscle.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Dejerine-Sottas disease in Orphanet.

Professional guidelines

PubMed

Chance PF
Suppl Clin Neurophysiol 2004;57:228-42. doi: 10.1016/s1567-424x(09)70360-5. PMID: 16106622
Pareyson D
Neurol Sci 2004 Jun;25(2):72-82. doi: 10.1007/s10072-004-0233-4. PMID: 15221625

Curated

Aretz S, Rautenstrauss B, Timmerman V
Eur J Hum Genet 2010 Sep;18(9) Epub 2010 May 26 doi: 10.1038/ejhg.2010.75. PMID: 20512157Free PMC Article

Recent clinical studies

Etiology

Hobbelink SMR, Brockley CR, Kennedy RA, Carroll K, de Valle K, Rao P, Davis MR, Laing NG, Voermans NC, Ryan MM, Yiu EM
Brain Behav 2018 Apr;8(4):e00919. Epub 2018 Feb 21 doi: 10.1002/brb3.919. PMID: 29670817Free PMC Article
Chance PF
Phys Med Rehabil Clin N Am 2001 May;12(2):277-91. PMID: 11345007
Keller MP, Chance PF
Semin Neurol 1999;19(4):353-62. doi: 10.1055/s-2008-1040850. PMID: 10716658
Keller MP, Chance PF
Brain Pathol 1999 Apr;9(2):327-41. doi: 10.1111/j.1750-3639.1999.tb00230.x. PMID: 10219749Free PMC Article
Chance PF, Reilly M
Curr Opin Neurol 1994 Oct;7(5):372-80. doi: 10.1097/00019052-199410000-00002. PMID: 7804455

Diagnosis

Pareyson D
Neurol Sci 2004 Jun;25(2):72-82. doi: 10.1007/s10072-004-0233-4. PMID: 15221625
Plante-Bordeneuve V, Said G
Muscle Nerve 2002 Nov;26(5):608-21. doi: 10.1002/mus.10197. PMID: 12402282
Chance PF
Phys Med Rehabil Clin N Am 2001 May;12(2):277-91. PMID: 11345007
Chance PF, Reilly M
Curr Opin Neurol 1994 Oct;7(5):372-80. doi: 10.1097/00019052-199410000-00002. PMID: 7804455
Satran R
Arch Neurol 1980 Feb;37(2):67-8. doi: 10.1001/archneur.1980.00500510025002. PMID: 7356409

Therapy

Gupta SC, Patchva S, Aggarwal BB
AAPS J 2013 Jan;15(1):195-218. Epub 2012 Nov 10 doi: 10.1208/s12248-012-9432-8. PMID: 23143785Free PMC Article
Burns J, Joseph PD, Rose KJ, Ryan MM, Ouvrier RA
Pediatr Neurol 2009 Oct;41(4):305-8. doi: 10.1016/j.pediatrneurol.2009.04.030. PMID: 19748054

Prognosis

Moldovan M, Pisciotta C, Pareyson D, Krarup C
Clin Neurophysiol 2020 Oct;131(10):2440-2451. Epub 2020 Aug 6 doi: 10.1016/j.clinph.2020.06.034. PMID: 32829291
Pareyson D
Neurol Sci 2004 Jun;25(2):72-82. doi: 10.1007/s10072-004-0233-4. PMID: 15221625
Plante-Bordeneuve V, Said G
Muscle Nerve 2002 Nov;26(5):608-21. doi: 10.1002/mus.10197. PMID: 12402282
Ikegami T, Ikeda H, Aoyama M, Matsuki T, Imota T, Fukuuchi Y, Amano T, Toyoshima I, Ishihara Y, Endoh H, Hayasaka K
Hum Genet 1998 Mar;102(3):294-8. doi: 10.1007/s004390050694. PMID: 9544841
Chance PF, Reilly M
Curr Opin Neurol 1994 Oct;7(5):372-80. doi: 10.1097/00019052-199410000-00002. PMID: 7804455

Clinical prediction guides

Hobbelink SMR, Brockley CR, Kennedy RA, Carroll K, de Valle K, Rao P, Davis MR, Laing NG, Voermans NC, Ryan MM, Yiu EM
Brain Behav 2018 Apr;8(4):e00919. Epub 2018 Feb 21 doi: 10.1002/brb3.919. PMID: 29670817Free PMC Article
Gupta SC, Patchva S, Aggarwal BB
AAPS J 2013 Jan;15(1):195-218. Epub 2012 Nov 10 doi: 10.1208/s12248-012-9432-8. PMID: 23143785Free PMC Article
Al-Thihli K, Rudkin T, Carson N, Poulin C, Melançon S, Der Kaloustian VM
Am J Med Genet A 2008 Sep 15;146A(18):2412-6. doi: 10.1002/ajmg.a.32456. PMID: 18698610
Marinho JL, Alonso Nieto JL, Calore EE
Sao Paulo Med J 2003 Sep 1;121(5):207-9. Epub 2003 Nov 5 doi: 10.1590/s1516-31802003000500006. PMID: 14666293Free PMC Article
Satran R
Arch Neurol 1980 Feb;37(2):67-8. doi: 10.1001/archneur.1980.00500510025002. PMID: 7356409

Supplemental Content

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    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • EuroGenetest, 2010
      Clinical utility gene card for: HMSN/HNPP HMSN types 1, 2, 3, 6 (CMT1,2,4, DSN, CHN, GAN, CCFDN, HNA); HNPP

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