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Charcot-Marie-Tooth disease type 4D(CMT4D; HMSNL)

MedGen UID:
371304
Concept ID:
C1832334
Disease or Syndrome
Synonyms: CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, AUTOSOMAL RECESSIVE, TYPE 4D; Charcot-Marie-Tooth Neuropathy Type 4D; Charcot-Marie-Tooth Neuropathy Type 4D (CMT4D); Neuropathy, hereditary motor and sensory, LOM type
SNOMED CT: Charcot-Marie-Tooth disease type 4D (715798007); Hereditary motor and sensory neuropathy Lom type (715798007)
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).
 
Gene (location): NDRG1 (8q24.22)
 
Monarch Initiative: MONDO:0011085
OMIM®: 601455
Orphanet: ORPHA99950

Definition

Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal recessive disorder of the peripheral nervous system characterized by early-onset distal muscle weakness and atrophy, foot deformities, and sensory loss affecting all modalities. Affected individuals develop deafness by the third decade of life (summary by Okamoto et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive Charcot-Marie-Tooth disease, see CMT4A (214400). [from OMIM]

Clinical features

From HPO
Abnormality of the hand
MedGen UID:
6715
Concept ID:
C0018564
Anatomical Abnormality
An abnormality affecting one or both hands.
Talipes cavus equinovarus
MedGen UID:
330444
Concept ID:
C1832342
Anatomical Abnormality
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Abnormal auditory evoked potentials
MedGen UID:
141758
Concept ID:
C0522216
Finding
An abnormality of the auditory evoked potentials, which are used to trace the signal generated by a sound, from the cochlear nerve, through the lateral lemniscus, to the medial geniculate nucleus, and to the cortex.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Axonal loss
MedGen UID:
316962
Concept ID:
C1832338
Finding
A reduction in the number of axons in the peripheral nervous system.
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 nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Abnormality of visual evoked potentials
MedGen UID:
105509
Concept ID:
C0522214
Finding
An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex.
Intraaxonal accumulation of curvilinear autofluorescent lipopigment storage material
MedGen UID:
892684
Concept ID:
C4024964
Finding
Curvilinear intracellular accumulation of autofluorescent lipopigment storage material within axons.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Charcot-Marie-Tooth disease type 4D in Orphanet.

Professional guidelines

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

Diagnosis

Li LX, Liu GL, Liu ZJ, Lu C, Wu ZY
Hum Mutat 2017 Nov;38(11):1569-1578. Epub 2017 Aug 23 doi: 10.1002/humu.23309. PMID: 28776325
Piscosquito G, Magri S, Saveri P, Milani M, Ciano C, Farina L, Taroni F, Pareyson D
J Peripher Nerv Syst 2017 Mar;22(1):47-50. doi: 10.1111/jns.12201. PMID: 27982524

Prognosis

Pravinbabu P, Holla VV, Phulpagar P, Kamble N, Netravathi M, Yadav R, Pal PK, Muthusamy B
Neurol Sci 2022 Jul;43(7):4463-4472. Epub 2022 Feb 11 doi: 10.1007/s10072-022-05893-4. PMID: 35149926

Clinical prediction guides

Pravinbabu P, Holla VV, Phulpagar P, Kamble N, Netravathi M, Yadav R, Pal PK, Muthusamy B
Neurol Sci 2022 Jul;43(7):4463-4472. Epub 2022 Feb 11 doi: 10.1007/s10072-022-05893-4. PMID: 35149926

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