Congenital myasthenic syndromes (CMS) are a heterogenous group of genetic disorders caused by mutations in several proteins that compose the neuromuscular junction (NMJ) apparatus on which synaptic formation and function depend. The majority are recessively inherited. The disorders of the NMJ cause weakness and fatigue.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Diseases of neuromuscular junction or muscle
Myasthenia gravis or certain specified neuromuscular junction disorders
8C61 Congenital myasthenic syndromes
H00770 Congenital myasthenic syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00770 Congenital myasthenic syndrome
nt06544 Neuroactive ligand signaling
H00770 Congenital myasthenic syndrome
Huze C, Bauche S, Richard P, Chevessier F, Goillot E, Gaudon K, Ben Ammar A, Chaboud A, Grosjean I, Lecuyer HA, Bernard V, Rouche A, Alexandri N, Kuntzer T, Fardeau M, Fournier E, Brancaccio A, Ruegg MA, Koenig J, Eymard B, Schaeffer L, Hantai D
Title
Identification of an agrin mutation that causes congenital myasthenia and affects synapse function.
Ohkawara B, Cabrera-Serrano M, Nakata T, Milone M, Asai N, Ito K, Ito M, Masuda A, Ito Y, Engel AG, Ohno K
Title
LRP4 third beta-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner.
O'Grady GL, Verschuuren C, Yuen M, Webster R, Menezes M, Fock JM, Pride N, Best HA, Benavides Damm T, Turner C, Lek M, Engel AG, North KN, Clarke NF, MacArthur DG, Kamsteeg EJ, Cooper ST
Title
Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome.
Chaouch A, Porcelli V, Cox D, Edvardson S, Scarcia P, De Grassi A, Pierri CL, Cossins J, Laval SH, Griffin H, Muller JS, Evangelista T, Topf A, Abicht A, Huebner A, von der Hagen M, Bushby K, Straub V, Horvath R, Elpeleg O, Palace J, Senderek J, Beeson D, Palmieri L, Lochmuller H
Title
Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission.
Salpietro V, Lin W, Delle Vedove A, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS, Pitt M, Bello OD, Rothman JE, Basel-Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H
Title
Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.
Autosomal dominant distal hereditary motor neuropathy (HMND) Autosomal recessive distal hereditary motor neuropathy (HMNR) X-linked distal hereditary motor neuropathy (HMNX)
Description
Distal hereditary motor neuropathies (dHMN) comprise a heterogenous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot-Marie-Tooth disease (CMT) [DS:H00264] and with juvenile forms of amyotrophic lateral sclerosis [DS:H00058] and hereditary spastic paraplegia [DS:H00266]. The causative genes with autosomal dominant, recessive, and X-linked patterns of inheritance have implicated proteins with diverse functions. Distal HMN are classified into phenotypic subtypes according to age at onset, mode of inheritance, and presence of additional features.
Category
Nervous system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
Motor neuron diseases or related disorders
8B61 Spinal muscular atrophy
H00856 Distal hereditary motor neuropathies
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06515 Regulation of kinetochore-microtubule interactions
H00856 Distal hereditary motor neuropathies
nt06541 Cytoskeleton in neurons
H00856 Distal hereditary motor neuropathies
nt06544 Neuroactive ligand signaling
H00856 Distal hereditary motor neuropathies
nt06546 IgSF CAM signaling
H00856 Distal hereditary motor neuropathies
Irobi J, Van Impe K, Seeman P, Jordanova A, Dierick I, Verpoorten N, Michalik A, De Vriendt E, Jacobs A, Van Gerwen V, Vennekens K, Mazanec R, Tournev I, Hilton-Jones D, Talbot K, Kremensky I, Van Den Bosch L, Robberecht W, Van Vandekerckhove J, Van Broeckhoven C, Gettemans J, De Jonghe P, Timmerman V
Title
Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy.
Evgrafov OV, Mersiyanova I, Irobi J, Van Den Bosch L, Dierick I, Leung CL, Schagina O, Verpoorten N, Van Impe K, Fedotov V, Dadali E, Auer-Grumbach M, Windpassinger C, Wagner K, Mitrovic Z, Hilton-Jones D, Talbot K, Martin JJ, Vasserman N, Tverskaya S, Polyakov A, Liem RK, Gettemans J, Robberecht W, De Jonghe P, Timmerman V
Title
Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy.
Antonellis A, Ellsworth RE, Sambuughin N, Puls I, Abel A, Lee-Lin SQ, Jordanova A, Kremensky I, Christodoulou K, Middleton LT, Sivakumar K, Ionasescu V, Funalot B, Vance JM, Goldfarb LG, Fischbeck KH, Green ED
Title
Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.
Beetz C, Pieber TR, Hertel N, Schabhuttl M, Fischer C, Trajanoski S, Graf E, Keiner S, Kurth I, Wieland T, Varga RE, Timmerman V, Reilly MM, Strom TM, Auer-Grumbach M
Title
Exome sequencing identifies a REEP1 mutation involved in distal hereditary motor neuropathy type V.
Windpassinger C, Auer-Grumbach M, Irobi J, Patel H, Petek E, Horl G, Malli R, Reed JA, Dierick I, Verpoorten N, Warner TT, Proukakis C, Van den Bergh P, Verellen C, Van Maldergem L, Merlini L, De Jonghe P, Timmerman V, Crosby AH, Wagner K
Title
Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.
de Fuenmayor-Fernandez de la Hoz CP, Lupo V, Bermejo-Guerrero L, Martin-Jimenez P, Hernandez-Lain A, Olive M, Gallardo E, Esteban-Perez J, Espinos C, Dominguez-Gonzalez C
Title
Distal hereditary motor neuronopathy as a new phenotype associated with variants in BAG3.
Deschauer M, Hengel H, Rupprich K, Kreiss M, Schlotter-Weigel B, Grimmel M, Admard J, Schneider I, Alhaddad B, Gazou A, Sturm M, Vorgerd M, Balousha G, Balousha O, Falna M, Kirschke JS, Kornblum C, Jordan B, Kraya T, Strom TM, Weis J, Schols L, Schara U, Zierz S, Riess O, Meitinger T, Haack TB
Title
Bi-allelic truncating mutations in VWA1 cause neuromyopathy.
Cortese A, Zhu Y, Rebelo AP, Negri S, Courel S, Abreu L, Bacon CJ, Bai Y, Bis-Brewer DM, Bugiardini E, Buglo E, Danzi MC, Feely SME, Athanasiou-Fragkouli A, Haridy NA, Isasi R, Khan A, Laura M, Magri S, Pipis M, Pisciotta C, Powell E, Rossor AM, Saveri P, Sowden JE, Tozza S, Vandrovcova J, Dallman J, Grignani E, Marchioni E, Scherer SS, Tang B, Lin Z, Al-Ajmi A, Schule R, Synofzik M, Maisonobe T, Stojkovic T, Auer-Grumbach M, Abdelhamed MA, Hamed SA, Zhang R, Manganelli F, Santoro L, Taroni F, Pareyson D, Houlden H, Herrmann DN, Reilly MM, Shy ME, Zhai RG, Zuchner S
Title
Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.
Maroofian R, Sarraf P, O'Brien TJ, Kamel M, Cakar A, Elkhateeb N, Lau T, Patil SJ, Record CJ, Horga A, Essid M, Selim L, Benrhouma H, Ben Younes T, Zifarelli G, Pagnamenta AT, Bauer P, Khundadze M, Mirecki A, Kamel SM, Elmonem MA, Ghayoor Karimiani E, Jamshidi Y, Offiah AC, Rossor AM, Youssef-Turki IB, Hubner CA, Munot P, Reilly MM, Brown AEX, Nagy S, Houlden H
Title
Reticulon 2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.
