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Charcot-Marie-Tooth disease X-linked recessive 5(CMTX5)

MedGen UID:
374254
Concept ID:
C1839566
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth Neuropathy X Type 5; Familial opticoacoustic nerve degeneration and polyneuropathy; Optic atrophy polyneuropathy deafness; Optic atrophy, neural deafness, and distal neurogenic amyotrophy; Optic atrophy, polyneuropathy, and deafness; Optic atrophy, sensorineural hearing loss and polyneuropathy; PRPS1-Related Charcot-Marie-Tooth Neuropathy X Type 5; Rosenberg Chutorian syndrome
SNOMED CT: X-linked Charcot-Marie-Tooth disease type 5 (763460007)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): PRPS1 (Xq22.3)
 
Monarch Initiative: MONDO:0010699
OMIM®: 311070
Orphanet: ORPHA99014

Definition

X-linked Charcot-Marie-Tooth neuropathy type 5 (CMTX5), part of the spectrum of PRPS1-related disorders, is characterized by peripheral neuropathy, early-onset (prelingual) bilateral profound sensorineural hearing loss, and optic neuropathy. The onset of peripheral neuropathy is between ages five and 12 years. The lower extremities are affected earlier and more severely than upper extremities. Initial manifestations often include foot drop or gait disturbance. Onset of visual impairment is between ages seven and 20 years. Intellect and life span are normal. Carrier females do not have findings of CMTX5. [from GeneReviews]

Additional description

From OMIM
The phenotype of X-linked Charcot-Marie-Tooth disease-5 typically comprises the triad of optic atrophy, deafness, and polyneuropathy. However, patients without optic atrophy have been reported (summary by Park et al., 2013). For a discussion of genetic heterogeneity of X-linked Charcot-Marie-Tooth disease, see CMTX1 (302800). See 165199 and 258650 for possible autosomal dominant and autosomal recessive forms of the disorder.  http://www.omim.org/entry/311070

Clinical features

From HPO
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).
Areflexia of lower limbs
MedGen UID:
347285
Concept ID:
C1856694
Finding
Inability to elicit tendon reflexes in the lower limbs.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Polyneuropathy
MedGen UID:
57502
Concept ID:
C0152025
Disease or Syndrome
A generalized disorder of peripheral nerves.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
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.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
Decreased phosphoribosylpyrophosphate synthetase level
MedGen UID:
1698029
Concept ID:
C5139359
Finding
Abnormally reduced level of the enzyme phosphoribosyl pyrophosphatesynthetase, which catalyzes the synthesis of PP-ribose-P from ATP and ribose-5-phosphate.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Progressive visual loss
MedGen UID:
326867
Concept ID:
C1839364
Finding
A reduction of previously attained ability to see.
Rod-cone dystrophy
MedGen UID:
1632921
Concept ID:
C4551714
Disease or Syndrome
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Charcot-Marie-Tooth disease X-linked recessive 5 in Orphanet.

Recent clinical studies

Diagnosis

Lerat J, Magdelaine C, Derouault P, Beauvais-Dzugan H, Bieth E, Acket B, Arne-Bes MC, Sturtz F, Lia AS
Mol Genet Genomic Med 2019 Sep;7(9):e875. Epub 2019 Jul 23 doi: 10.1002/mgg3.875. PMID: 31338985Free PMC Article

Prognosis

Lerat J, Magdelaine C, Derouault P, Beauvais-Dzugan H, Bieth E, Acket B, Arne-Bes MC, Sturtz F, Lia AS
Mol Genet Genomic Med 2019 Sep;7(9):e875. Epub 2019 Jul 23 doi: 10.1002/mgg3.875. PMID: 31338985Free PMC Article

Clinical prediction guides

Lerat J, Magdelaine C, Derouault P, Beauvais-Dzugan H, Bieth E, Acket B, Arne-Bes MC, Sturtz F, Lia AS
Mol Genet Genomic Med 2019 Sep;7(9):e875. Epub 2019 Jul 23 doi: 10.1002/mgg3.875. PMID: 31338985Free PMC Article

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