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Charcot-Marie-Tooth disease X-linked dominant 6(CMTX6)

MedGen UID:
813032
Concept ID:
C3806702
Disease or Syndrome
Synonym: CHARCOT-MARIE-TOOTH NEUROPATHY, X-LINKED DOMINANT, 6
SNOMED CT: X-linked Charcot-Marie-Tooth disease type 6 (763347000)
Modes of inheritance:
X-linked dominant inheritance
MedGen UID:
376232
Concept ID:
C1847879
Finding
Source: Orphanet
A mode of inheritance that is observed for dominant traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked dominant disorders tend to manifest very severely in affected males. The severity of manifestation in females may depend on the degree of skewed X inactivation.
 
Gene (location): PDK3 (Xp22.11)
 
Monarch Initiative: MONDO:0010479
OMIM®: 300905
Orphanet: ORPHA352675

Definition

A rare genetic principally axonal peripheral sensorimotor neuropathy with an X-linked dominant inheritance pattern and the childhood-onset of slowly progressive, moderate to severe, distal muscle weakness and atrophy of the lower extremities, as well as distal, pan modal sensory abnormalities, bilateral foot deformities (pes cavus, clawed toes), absent ankle reflexes and gait abnormalities (steppage gait). Females are usually asymptomatic or only present mild manifestations (mild postural hand tremor, mild wasting of hand intrinsic muscles). [from SNOMEDCT_US]

Clinical features

From HPO
Hand muscle weakness
MedGen UID:
66798
Concept ID:
C0239831
Finding
Reduced strength of the musculature of the hand.
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
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).
Decreased Achilles reflex
MedGen UID:
324765
Concept ID:
C1837323
Finding
Decreased intensity of the Achilles reflex (also known as the ankle jerk reflex), which can be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
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.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
Hand tremor
MedGen UID:
68689
Concept ID:
C0239842
Finding
An unintentional, oscillating to-and-fro muscle movement affecting the hand.
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.
Impaired pain sensation
MedGen UID:
373348
Concept ID:
C1837522
Finding
Reduced ability to perceive painful stimuli.
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.
Distal lower limb amyotrophy
MedGen UID:
324515
Concept ID:
C1836451
Disease or Syndrome
Muscular atrophy of distal leg muscles.
Intrinsic hand muscle atrophy
MedGen UID:
351202
Concept ID:
C1864716
Finding
Atrophy of the intrinsic muscle groups of the hand, comprising the thenar and hypothenar muscles; the interossei muscles; and the lumbrical muscles.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCharcot-Marie-Tooth disease X-linked dominant 6
Follow this link to review classifications for Charcot-Marie-Tooth disease X-linked dominant 6 in Orphanet.

Professional guidelines

PubMed

Hahn AF, Bolton CF, White CM, Brown WF, Tuuha SE, Tan CC, Ainsworth PJ
Ann N Y Acad Sci 1999 Sep 14;883:366-82. PMID: 10586261

Recent clinical studies

Etiology

Rudnik-Schöneborn S, Thiele S, Walter MC, Reinecke L, Sereda M, Schöneborn R, Elbracht M
Eur J Neurol 2020 Aug;27(8):1390-1396. Epub 2020 Jun 16 doi: 10.1111/ene.14317. PMID: 32400062Free PMC Article
Borgulová I, Putzová M, Soldatova I, Stejskal D
Med Clin (Barc) 2018 Mar 23;150(6):215-219. Epub 2017 Aug 8 doi: 10.1016/j.medcli.2017.06.041. PMID: 28797703
Rossor AM, Kalmar B, Greensmith L, Reilly MM
J Neurol Neurosurg Psychiatry 2012 Jan;83(1):6-14. Epub 2011 Oct 25 doi: 10.1136/jnnp-2011-300952. PMID: 22028385
Casasnovas C, Cano LM, Albertí A, Céspedes M, Rigo G
Foot Ankle Spec 2008 Dec;1(6):350-4. Epub 2008 Oct 22 doi: 10.1177/1938640008326247. PMID: 19825739
Hahn AF, Bolton CF, White CM, Brown WF, Tuuha SE, Tan CC, Ainsworth PJ
Ann N Y Acad Sci 1999 Sep 14;883:366-82. PMID: 10586261

Diagnosis

Rudnik-Schöneborn S, Thiele S, Walter MC, Reinecke L, Sereda M, Schöneborn R, Elbracht M
Eur J Neurol 2020 Aug;27(8):1390-1396. Epub 2020 Jun 16 doi: 10.1111/ene.14317. PMID: 32400062Free PMC Article
Borgulová I, Putzová M, Soldatova I, Stejskal D
Med Clin (Barc) 2018 Mar 23;150(6):215-219. Epub 2017 Aug 8 doi: 10.1016/j.medcli.2017.06.041. PMID: 28797703
Liu L, Zhang R
Neurosci Bull 2014 Dec;30(6):999-1009. Epub 2014 Oct 17 doi: 10.1007/s12264-014-1475-7. PMID: 25326399Free PMC Article
Rossor AM, Kalmar B, Greensmith L, Reilly MM
J Neurol Neurosurg Psychiatry 2012 Jan;83(1):6-14. Epub 2011 Oct 25 doi: 10.1136/jnnp-2011-300952. PMID: 22028385
Casasnovas C, Cano LM, Albertí A, Céspedes M, Rigo G
Foot Ankle Spec 2008 Dec;1(6):350-4. Epub 2008 Oct 22 doi: 10.1177/1938640008326247. PMID: 19825739

Therapy

Roses AD, Pericak-Vance MA, Yamaoka LH, Stubblefield E, Stajich J, Vance JM, Roses MJ, Carter DB
Muscle Nerve 1983 Jun;6(5):339-55. doi: 10.1002/mus.880060503. PMID: 6310392

Prognosis

Casasnovas C, Cano LM, Albertí A, Céspedes M, Rigo G
Foot Ankle Spec 2008 Dec;1(6):350-4. Epub 2008 Oct 22 doi: 10.1177/1938640008326247. PMID: 19825739
Takashima H, Nakagawa M, Umehara F, Hirata K, Suehara M, Mayumi H, Yoshishige K, Matsuyama W, Saito M, Jonosono M, Arimura K, Osame M
Acta Neurol Scand 2003 Jan;107(1):31-7. doi: 10.1034/j.1600-0404.2003.01317.x. PMID: 12542510

Clinical prediction guides

Kennerson ML, Kim EJ, Siddell A, Kidambi A, Kim SM, Hong YB, Hwang SH, Chung KW, Choi BO
J Peripher Nerv Syst 2016 Mar;21(1):45-51. doi: 10.1111/jns.12160. PMID: 26801680
Dubourg O, Tardieu S, Birouk N, Gouider R, Léger JM, Maisonobe T, Brice A, Bouche P, LeGuern E
Brain 2001 Oct;124(Pt 10):1958-67. doi: 10.1093/brain/124.10.1958. PMID: 11571214
Hahn AF, Bolton CF, White CM, Brown WF, Tuuha SE, Tan CC, Ainsworth PJ
Ann N Y Acad Sci 1999 Sep 14;883:366-82. PMID: 10586261
Omori Y, Mesnil M, Yamasaki H
Mol Biol Cell 1996 Jun;7(6):907-16. doi: 10.1091/mbc.7.6.907. PMID: 8816997Free PMC Article
Ionasescu VV, Trofatter J, Haines JL, Summers AM, Ionasescu R, Searby C
Am J Hum Genet 1991 Jun;48(6):1075-83. PMID: 1674639Free PMC Article

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