Full Report

Format

Full Report
Summary (Text)
Summary (XML)

Send to:

Choose Destination

File
Clipboard
Collections

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. See: This record X-linked recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	PRPS1 (Xq22.3)

Monarch Initiative:	MONDO:0010699
OMIM®:	311070
Orphanet:	ORPHA99014

Definition

Phosphoribosylpyrophosphate synthetase (PRS) deficiency, an X-linked disorder, is a phenotypic continuum comprising three disorders previously thought to be clinically distinct: Arts syndrome, Charcot-Marie-Tooth neuropathy X type 5 (CMTX5), and X-linked nonsyndromic sensorineural hearing loss (DFNX1). In affected males, the PRS deficiency phenotypic spectrum ranges from severe congenital profound sensorineural hearing loss, intellectual disability, delayed motor development, and progressive ophthalmologic involvement (retinal dystrophy and optic atrophy) to normal cognitive abilities and relatively later-onset, somewhat milder manifestations, such as mild sensorineural hearing loss, peripheral neuropathy, and gait ataxia. Heterozygous females can show isolated and/or milder manifestations in the PRS deficiency spectrum. To date, 40 families with PRS deficiency have been reported. [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).

See: Feature record | Search on this feature

Areflexia of lower limbs

MedGen UID:: 347285
•Concept ID:: C1856694
•: Finding

Inability to elicit tendon reflexes in the lower limbs.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Hearing impairment

MedGen UID:: 235586
•Concept ID:: C1384666
•: Disease or Syndrome

A decreased magnitude of the sensory perception of sound.

See: Feature record | Search on this feature

Polyneuropathy

MedGen UID:: 57502
•Concept ID:: C0152025
•: Disease or Syndrome

A generalized disorder of peripheral nerves.

See: Feature record | Search on this feature

Gait disturbance

MedGen UID:: 107895
•Concept ID:: C0575081
•: Finding

The term gait disturbance can refer to any disruption of the ability to walk.

See: Feature record | Search on this feature

Segmental peripheral demyelination/remyelination

MedGen UID:: 335873
•Concept ID:: C1843077
•: Finding

A segmental pattern of demyelination and regeneration (remyelination) affecting peripheral nerves.

See: Feature record | Search on this feature

Distal sensory impairment

MedGen UID:: 335722
•Concept ID:: C1847584
•: Finding

An abnormal reduction in sensation in the distal portions of the extremities.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Motor delay

MedGen UID:: 381392
•Concept ID:: C1854301
•: Finding

A type of Developmental delay characterized by a delay in acquiring motor skills.

See: Feature record | Search on this feature

Distal muscle weakness

MedGen UID:: 140883
•Concept ID:: C0427065
•: Finding

Reduced strength of the musculature of the distal extremities.

See: Feature record | Search on this feature

Distal amyotrophy

MedGen UID:: 338530
•Concept ID:: C1848736
•: Disease or Syndrome

Muscular atrophy affecting muscles in the distal portions of the extremities.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Progressive visual loss

MedGen UID:: 326867
•Concept ID:: C1839364
•: Finding

A reduction of previously attained ability to see.

See: Feature record | Search on this feature

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.

See: Feature record | Search on this feature

Show all Hide all

Abnormality of limbs
- Areflexia of lower limbs
- Pes cavus
Abnormality of metabolism/homeostasis
- Decreased phosphoribosylpyrophosphate synthetase level
Abnormality of the eye
Abnormality of the musculoskeletal system
- Distal amyotrophy
- Distal muscle weakness
Abnormality of the nervous system
Ear malformation
- Hearing impairment
- Sensorineural hearing loss disorder

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVCharcot-Marie-Tooth disease

Charcot-Marie-Tooth disease type X
- Charcot-Marie-Tooth disease X-linked recessive 5

Follow this link to review classifications for Charcot-Marie-Tooth disease X-linked recessive 5 in Orphanet.

Recent clinical studies

Diagnosis

New PRPS1 variant p.(Met68Leu) located in the dimerization area identified in a French CMTX5 patient.

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: 31338985 Free PMC Article

See all (1)