Table 3.
Proposed revision of Orphanet hierarchy below ORPHA:590 (Congenital myasthenic syndrome)
| ORPHA number | Typology | Root | Level 1 | Level 2 | Level 3 | Level 4 |
|---|---|---|---|---|---|---|
| ORPHA:590 | Group of phenomes | Congenital myasthenic syndrome | ||||
| ORPHA:98913 | Group of phenomes | Postsynaptic congenital myasthenic syndromes | ||||
| NEW | Group of phenomes | Congenital myasthenic syndromes with kinetic defect | ||||
| NEW | Group of phenomes | Fast-channel congenital myasthenic syndromes | ||||
| NEW | Disease | Fast-channel congenital myasthenic syndrome due to an acetylcholine receptor defect caused by a pathogenic variant in CHRNA1 | ||||
| NEW | Disease | Fast-channel congenital myasthenic syndrome due to an acetylcholine receptor defect caused by a pathogenic variant in CHRNB1 | ||||
| NEW | Disease | Fast-channel congenital myasthenic syndrome due to an acetylcholine receptor defect caused by a pathogenic variant in CHRND | ||||
| NEW | Disease | Fast-channel congenital myasthenic syndrome due to an acetylcholine receptor defect caused by a pathogenic variant in CHRNE | ||||
| NEW | Group of phenomes | Slow-channel congenital myasthenic syndromes | ||||
| NEW | Disease | Slow-channel congenital myasthenic syndrome due to an acetylcholine receptor defect caused by a pathogenic variant in CHRNA1 | ||||
| NEW | Disease | Slow-channel congenital myasthenic syndrome due to an acetylcholine receptor defect caused by a pathogenic variant in CHRNB1 | ||||
| NEW | Disease | Slow-channel congenital myasthenic syndrome due to an acetylcholine receptor defect caused by a pathogenic variant in CHRND | ||||
| NEW | Disease | Slow-channel congenital myasthenic syndrome due to an acetylcholine receptor defect caused by a pathogenic variant in CHRNE | ||||
| NEW | Group of phenomes | Congenital myasthenic syndromes with kinetic defect due to reduced ion channel conductance | ||||
| NEW | Disease | Congenital myasthenic syndrome with kinetic defect due to reduced ion channel conductance caused by pathogenic variants in CHRNE | ||||
| NEW | Group of phenomes | Congenital myasthenic syndromes with primary acetylcholine receptor deficiency | ||||
| NEW | Disease | Congenital myasthenic syndrome due to primary acetylcholine receptor deficiency caused by pathogenic variants in CHRNA1 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to primary acetylcholine receptor deficiency caused by pathogenic variants in CHRNB1 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to primary acetylcholine receptor deficiency caused by pathogenic variants in CHRND | ||||
| NEW | Disease | Congenital myasthenic syndrome due to primary acetylcholine receptor deficiency caused by pathogenic variants in CHRNE | ||||
| NEW | Group of phenomes | Congenital myasthenic syndromes due to primary or secondary defects in acetylcholine receptor clustering | ||||
| NEW | Disease | Congenital myasthenic syndrome due to defects in acetylcholine receptor clustering caused by pathogenic variants in CHRND | ||||
| NEW | Disease | Congenital myasthenic syndrome due to endplate rapsyn deficiency caused by pathogenic variants in RAPSN | ||||
| NEW | Group of phenomes | Congenital myasthenic syndromes due to defects in endplate development and maintenance | ||||
| NEW | Disease | Congenital myasthenic syndrome due to agrin deficiency caused by pathogenic variants in AGRN | ||||
| NEW | Disease | Congenital myasthenic syndrome due to defects in low-density lipoprotein receptor-related protein 4 caused by pathogenic variants in LRP4 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to defects in muscle-specific kinase caused by pathogenic variants in MUSK | ||||
| NEW | Disease | Congenital myasthenic syndrome due to defects in docking protein 7 caused by pathogenic variants in DOK7 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to plectin deficiency caused by pathogenic variants in PLEC1 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a sodium channel 1.4 defect caused by pathogenic variants in SCN4A | ||||
| ORPHA:98914 | Group of phenomes | Presynaptic congenital myasthenic syndromes | ||||
| NEW | Group of phenomes | Congenital myasthenic syndromes due to defective axonal transport | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a defect in Myosin 9A caused by pathogenic variants in MYO9A | ||||
| NEW | Group of phenomes | Congenital myasthenic syndromes due to defective synthesis or recycling of acetylcholine | ||||
| NEW | Disease | Congenital myasthenic syndrome due to endplate choline acetyltransferase deficiency caused by pathogenic variants in CHAT | ||||
| NEW | Disease | Congenital myasthenic syndrome caused by pathogenic variants in PREPL that predict reduced filling of synaptic vesicles with ACh | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a choline transporter defect caused by pathogenic variants in SLC5A7 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a vesicular acetylcholine transporter defect caused by pathogenic variants in SLC18A3 | ||||
| NEW | Group of phenomes | Congenital myasthenic syndromes due to defective synaptic vesicles exocytosis | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a synaptosomal-associated protein 25 defect caused by pathogenic variants in SNAP25B | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a synaptotagmin defect caused by a pathogenic variant in SYT2 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a mammalian uncoordinated-13 protein defect caused by a pathogenic variant in UNC13A | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a vesicle associated membrane protein 1 defect caused by a pathogenic variant in VAMP1 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a mitochondrial citrate carrier defect caused by pathogenic variants in SLC25A1 | ||||
| ORPHA:98915 | Group of phenomes | Synaptic and basal lamina associated congenital myasthenic syndromesa | ||||
| NEW | Disease | Congenital myasthenic syndrome due to endplate acetylcholinesterase deficiency caused by pathogenic variants in COLQ | ||||
| NEW | Disease | Congenital myasthenic syndrome due to collagen 13 defects caused by pathogenic variants in COL13A1 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to laminin beta 2 deficiency caused by pathogenic variants in LAMB2 | ||||
| ORPHA:353327 | Group of phenomes | Congenital myasthenic syndromes with glycosylation defect | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a defect of glycosylation caused by pathogenic variants in GFPT1 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a defect of glycosylation caused by pathogenic variants in DPAGT1 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a defect of glycosylation caused by pathogenic variants in ALG2 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a defect of glycosylation caused by pathogenic variants in ALG14 | ||||
| NEW | Disease | Congenital myasthenic syndrome due to a defect of glycosylation caused by pathogenic variants in GMPPB |
aname of group updated from “synaptic congenital myasthenic syndromes”