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Charcot-Marie-Tooth disease, type IF(CMT1F)

MedGen UID:
334337
Concept ID:
C1843164
Disease or Syndrome
Synonyms: Charcot-Marie-Tooth disease, demyelinating, Type 1F; Charcot-Marie-Tooth disease, type 1F; Charcot-Marie-Tooth Neuropathy Type 1; Charcot-Marie-Tooth Neuropathy Type 1F/2E; CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 1F; CMT 1F; CMT1F
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, Orphanet
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
 
Gene (location): NEFL (8p21.2)
OMIM®: 607734
Orphanet: ORPHA101085

Additional descriptions

From GeneReviews
Charcot-Marie-Tooth neuropathy type 2E/1F (CMT2E/1F) is characterized by a progressive peripheral motor and sensory neuropathy with variable clinical and electrophysiologic expression. Disease onset ranges from the first to the fifth decade of life; in some cases disease onset can be in infancy. Affected individuals have difficulty walking and running because of progressive distal weakness and wasting of the muscles of the lower limbs. Paresis in the distal part of the lower limbs varies from mild weakness to a complete paralysis of the distal muscle groups. Tendon reflexes are diminished or absent. Sensory signs are not prominent but are present in all affected individuals. Pes cavus, hammer toes, and claw hands are frequently observed. Ambulation is generally preserved.  http://www.ncbi.nlm.nih.gov/books/NBK1187
From GHR
Charcot-Marie-Tooth disease is a group of progressive disorders that affect the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves can result in loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands. Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity, even among members of the same family. Some people never realize they have the disorder, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy. Typically, the earliest symptoms of Charcot-Marie-Tooth disease involve balance difficulties, clumsiness, and muscle weakness in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (or gait) and increase the risk of ankle injuries and tripping. As the disease progresses, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair. Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with this disorder typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In some cases, affected individuals experience gradual hearing loss, deafness, or loss of vision. There are several types of Charcot-Marie-Tooth disease. Type 1 Charcot-Marie-Tooth disease (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to conduct nerve impulses. These abnormalities slow the transmission of nerve impulses. Type 2 Charcot-Marie-Tooth disease (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body and transmits nerve impulses. These abnormalities reduce the strength of the nerve impulse. Type 4 Charcot-Marie-Tooth disease (CMT4) affects either the axon or myelin and is distinguished from the other types by its pattern of inheritance. In intermediate forms of Charcot-Marie-Tooth disease, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both axons and myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in a gene on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) are distinguished by the specific gene that is altered. Sometimes other, more historical names are used to describe this disorder. For example, Roussy-Levy syndrome is a form of Charcot-Marie-Tooth disease defined by the additional feature of rhythmic shaking (tremors). Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called Charcot-Marie-Tooth disease type 3 (CMT3). Depending on the specific gene that is altered, this severe, early onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome. Some researchers believe that this condition is not actually a form of Charcot-Marie-Tooth disease. Instead, they classify it as a separate disorder characterized by peripheral nerve problems, deafness, and vision loss.  http://ghr.nlm.nih.gov/condition/charcot-marie-tooth-disease

Clinical features

Hyporeflexia
MedGen UID:
101804
Concept ID:
C0151888
Finding
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Distal sensory impairment
MedGen UID:
373064
Concept ID:
C1836340
Finding
Segmental peripheral demyelination/remyelination
MedGen UID:
335873
Concept ID:
C1843077
Finding
Myelin outfoldings
MedGen UID:
334341
Concept ID:
C1843168
Finding
Clusters of axonal regeneration
MedGen UID:
335897
Concept ID:
C1843169
Finding
Onion bulb formation
MedGen UID:
376237
Concept ID:
C1847906
Finding
Motor delay
MedGen UID:
504779
Concept ID:
CN001164
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Decreased number of peripheral myelinated nerve fibers
MedGen UID:
505527
Concept ID:
CN003050
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:
500951
Concept ID:
CN003094
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Distal amyotrophy
MedGen UID:
505575
Concept ID:
CN003339
Finding
Muscular atrophy affecting muscles in the distal portions of the extremities.
Pes cavus
MedGen UID:
425071
Concept ID:
CN001601
Finding
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.

Term Hierarchy

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

Recent clinical studies

Etiology

Yiu EM, Brockley CR, Lee KJ, Carroll K, de Valle K, Kennedy R, Rao P, Delatycki MB, Ryan MM
Neurology 2015 Feb 10;84(6):569-74. Epub 2015 Jan 9 doi: 10.1212/WNL.0000000000001236. [Epub ahead of print] PMID: 25576636
Zhan Y, Zi X, Hu Z, Peng Y, Wu L, Li X, Jiang M, Liu L, Xie Y, Xia K, Tang B, Zhang R
Muscle Nerve 2015 Jul;52(1):69-75. Epub 2015 Mar 31 doi: 10.1002/mus.24550. [Epub ahead of print] PMID: 25522693
Attarian S, Vallat JM, Magy L, Funalot B, Gonnaud PM, Lacour A, Péréon Y, Dubourg O, Pouget J, Micallef J, Franques J, Lefebvre MN, Ghorab K, Al-Moussawi M, Tiffreau V, Preudhomme M, Magot A, Leclair-Visonneau L, Stojkovic T, Bossi L, Lehert P, Gilbert W, Bertrand V, Mandel J, Milet A, Hajj R, Boudiaf L, Scart-Grès C, Nabirotchkin S, Guedj M, Chumakov I, Cohen D
Orphanet J Rare Dis 2014 Dec 18;9:199. doi: 10.1186/s13023-014-0199-0. [Epub ahead of print] PMID: 25519680Free PMC Article
Laurà M, Hutton EJ, Blake J, Lunn MP, Fox Z, Pareyson D, Solari A, Radice D, Koltzenburg M, Reilly MM
Muscle Nerve 2014 Sep;50(3):366-71. Epub 2014 May 15 doi: 10.1002/mus.24169. [Epub ahead of print] PMID: 24395492
Shahrizaila N, Samulong S, Tey S, Suan LC, Meng LK, Goh KJ, Ahmad-Annuar A
Muscle Nerve 2014 Feb;49(2):198-201. Epub 2013 Oct 4 doi: 10.1002/mus.23892. [Epub ahead of print] PMID: 23649551

Diagnosis

Yiu EM, Brockley CR, Lee KJ, Carroll K, de Valle K, Kennedy R, Rao P, Delatycki MB, Ryan MM
Neurology 2015 Feb 10;84(6):569-74. Epub 2015 Jan 9 doi: 10.1212/WNL.0000000000001236. [Epub ahead of print] PMID: 25576636
Zhan Y, Zi X, Hu Z, Peng Y, Wu L, Li X, Jiang M, Liu L, Xie Y, Xia K, Tang B, Zhang R
Muscle Nerve 2015 Jul;52(1):69-75. Epub 2015 Mar 31 doi: 10.1002/mus.24550. [Epub ahead of print] PMID: 25522693
García A, Pelayo-Negro AL, Álvarez-Paradelo S, Antolín FM, Berciano J
Muscle Nerve 2015 Jul;52(1):39-44. Epub 2015 May 14 doi: 10.1002/mus.24499. [Epub ahead of print] PMID: 25363904
Chen M, Wu J, Liang N, Tang L, Chen Y, Chen H, Wei W, Wei T, Huang H, Yi X, Qi M
Genomics Proteomics Bioinformatics 2014 Oct;12(5):221-7. Epub 2014 Oct 28 doi: 10.1016/j.gpb.2014.09.003. [Epub ahead of print] PMID: 25462154Free PMC Article
Al-Mateen M, Craig AK, Chance PF
J Child Neurol 2014 Mar;29(3):342-8. Epub 2013 Feb 11 doi: 10.1177/0883073812474343. [Epub ahead of print] PMID: 23400245

Therapy

Attarian S, Vallat JM, Magy L, Funalot B, Gonnaud PM, Lacour A, Péréon Y, Dubourg O, Pouget J, Micallef J, Franques J, Lefebvre MN, Ghorab K, Al-Moussawi M, Tiffreau V, Preudhomme M, Magot A, Leclair-Visonneau L, Stojkovic T, Bossi L, Lehert P, Gilbert W, Bertrand V, Mandel J, Milet A, Hajj R, Boudiaf L, Scart-Grès C, Nabirotchkin S, Guedj M, Chumakov I, Cohen D
Orphanet J Rare Dis 2014 Dec 18;9:199. doi: 10.1186/s13023-014-0199-0. [Epub ahead of print] PMID: 25519680Free PMC Article
Inglese J, Dranchak P, Moran JJ, Jang SW, Srinivasan R, Santiago Y, Zhang L, Guha R, Martinez N, MacArthur R, Cost GJ, Svaren J
ACS Chem Biol 2014 Nov 21;9(11):2594-602. Epub 2014 Sep 16 doi: 10.1021/cb5005492. [Epub ahead of print] PMID: 25188731Free PMC Article
Mannil M, Solari A, Leha A, Pelayo-Negro AL, Berciano J, Schlotter-Weigel B, Walter MC, Rautenstrauss B, Schnizer TJ, Schenone A, Seeman P, Kadian C, Schreiber O, Angarita NG, Fabrizi GM, Gemignani F, Padua L, Santoro L, Quattrone A, Vita G, Calabrese D; CMT-TRIAAL/CMT-TRAUK Group, Young P, Laurà M, Haberlová J, Mazanec R, Paulus W, Beissbarth T, Shy ME, Reilly MM, Pareyson D, Sereda MW
Neuromuscul Disord 2014 Nov;24(11):1003-17. Epub 2014 Jun 19 doi: 10.1016/j.nmd.2014.06.431. [Epub ahead of print] PMID: 25085517
Laurà M, Hutton EJ, Blake J, Lunn MP, Fox Z, Pareyson D, Solari A, Radice D, Koltzenburg M, Reilly MM
Muscle Nerve 2014 Sep;50(3):366-71. Epub 2014 May 15 doi: 10.1002/mus.24169. [Epub ahead of print] PMID: 24395492
Lewis RA, McDermott MP, Herrmann DN, Hoke A, Clawson LL, Siskind C, Feely SM, Miller LJ, Barohn RJ, Smith P, Luebbe E, Wu X, Shy ME; Muscle Study Group
JAMA Neurol 2013 Aug;70(8):981-7. doi: 10.1001/jamaneurol.2013.3178. PMID: 23797954Free PMC Article

Prognosis

Yiu EM, Brockley CR, Lee KJ, Carroll K, de Valle K, Kennedy R, Rao P, Delatycki MB, Ryan MM
Neurology 2015 Feb 10;84(6):569-74. Epub 2015 Jan 9 doi: 10.1212/WNL.0000000000001236. [Epub ahead of print] PMID: 25576636
Cottenie E, Kochanski A, Jordanova A, Bansagi B, Zimon M, Horga A, Jaunmuktane Z, Saveri P, Rasic VM, Baets J, Bartsakoulia M, Ploski R, Teterycz P, Nikolic M, Quinlivan R, Laura M, Sweeney MG, Taroni F, Lunn MP, Moroni I, Gonzalez M, Hanna MG, Bettencourt C, Chabrol E, Franke A, von Au K, Schilhabel M, Kabzińska D, Hausmanowa-Petrusewicz I, Brandner S, Lim SC, Song H, Choi BO, Horvath R, Chung KW, Zuchner S, Pareyson D, Harms M, Reilly MM, Houlden H
Am J Hum Genet 2014 Nov 6;95(5):590-601. Epub 2014 Oct 30 doi: 10.1016/j.ajhg.2014.10.002. [Epub ahead of print] PMID: 25439726Free PMC Article
Bombelli F, Stojkovic T, Dubourg O, Echaniz-Laguna A, Tardieu S, Larcher K, Amati-Bonneau P, Latour P, Vignal O, Cazeneuve C, Brice A, Leguern E
JAMA Neurol 2014 Aug;71(8):1036-42. doi: 10.1001/jamaneurol.2014.629. PMID: 24957169
Brewer MH, Ma KH, Beecham GW, Gopinath C, Baas F, Choi BO, Reilly MM, Shy ME, Züchner S, Svaren J, Antonellis A
Hum Mol Genet 2014 Oct 1;23(19):5171-87. Epub 2014 May 15 doi: 10.1093/hmg/ddu240. [Epub ahead of print] PMID: 24833716Free PMC Article
Martikainen MH, Kytövuori L, Majamaa K
Neuromuscul Disord 2014 Apr;24(4):360-4. Epub 2014 Jan 27 doi: 10.1016/j.nmd.2014.01.007. [Epub ahead of print] PMID: 24530046

Clinical prediction guides

Yiu EM, Brockley CR, Lee KJ, Carroll K, de Valle K, Kennedy R, Rao P, Delatycki MB, Ryan MM
Neurology 2015 Feb 10;84(6):569-74. Epub 2015 Jan 9 doi: 10.1212/WNL.0000000000001236. [Epub ahead of print] PMID: 25576636
Pla-Martín D, Calpena E, Lupo V, Márquez C, Rivas E, Sivera R, Sevilla T, Palau F, Espinós C
Hum Mol Genet 2015 Jan 1;24(1):213-29. Epub 2014 Aug 28 doi: 10.1093/hmg/ddu440. [Epub ahead of print] PMID: 25168384
Leal A, Berghoff C, Berghoff M, Rojas-Araya M, Carolina O, Heuss D, Del Valle G, Rautenstrauss B
Rev Biol Trop 2014 Dec;62(4):1285-93. PMID: 25720167
Attarian S, Vallat JM, Magy L, Funalot B, Gonnaud PM, Lacour A, Péréon Y, Dubourg O, Pouget J, Micallef J, Franques J, Lefebvre MN, Ghorab K, Al-Moussawi M, Tiffreau V, Preudhomme M, Magot A, Leclair-Visonneau L, Stojkovic T, Bossi L, Lehert P, Gilbert W, Bertrand V, Mandel J, Milet A, Hajj R, Boudiaf L, Scart-Grès C, Nabirotchkin S, Guedj M, Chumakov I, Cohen D
Orphanet J Rare Dis 2014 Dec 18;9:199. doi: 10.1186/s13023-014-0199-0. [Epub ahead of print] PMID: 25519680Free PMC Article
Bombelli F, Stojkovic T, Dubourg O, Echaniz-Laguna A, Tardieu S, Larcher K, Amati-Bonneau P, Latour P, Vignal O, Cazeneuve C, Brice A, Leguern E
JAMA Neurol 2014 Aug;71(8):1036-42. doi: 10.1001/jamaneurol.2014.629. PMID: 24957169

Recent systematic reviews

White CM, van Doorn PA, Garssen MP, Stockley RC
Cochrane Database Syst Rev 2014 Dec 18;12:CD008146. doi: 10.1002/14651858.CD008146.pub2. PMID: 25519471
Rose KJ, Burns J, Wheeler DM, North KN
Cochrane Database Syst Rev 2010 Feb 17;(2):CD006973. doi: 10.1002/14651858.CD006973.pub2. PMID: 20166090
Kuruvilla G, Perry S, Wilson B, El-Hakim H
Arch Otolaryngol Head Neck Surg 2009 Jan;135(1):101-5. doi: 10.1001/archoto.2008.514. PMID: 19153315
Szigeti K, Garcia CA, Lupski JR
Genet Med 2006 Feb;8(2):86-92. doi: 10.109701.gim.0000200160.29385.73. PMID: 16481890
Neuromuscul Disord 1998 Aug;8(6):426-31. PMID: 9713862

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