IllnessEpilepsy, progressive myoclonic; differentiaöl diagnosis

NGS +

CSTB gene: often 12mer repeat [(CCCCGCCCCGCG)n] expansion

Patients with progressive myoclonus, Unverricht-Lundborg, epilepsy (EPM1) show initial symptoms at 6-15 years of age with increasingly frequent episodes of myoclonus that, for example, progressively interfere with walking. In the further progression, ataxia, dysarthria, intention tremor, depression and intellectual decline may develop. Depending on the severity of the disease and response to treatment, life expectancy may be normal. EPM1 diagnosis is frequently (90%) made by biallelic elongated CCC CGC CCC GCG (dodecamer) expansions in the CSTB gene or compound heterozygosity for a CSTB dodecamer expansion and a CSTB mutation (10%). 2-3 dodecamer repeats are normal alleles, indeterminate diagnostic significance have alleles comprising 12-17 dodecamer repeats (unstable but not clinically confirmed). Pathogenic are ≥30 dodecamer repeats which exhibit full penetrance. The diagnostic yield has been infrequently described at <70%. Inconspicuous findings exclude by no means the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1142/

https://www.ncbi.nlm.nih.gov/books/NBK1389/

https://www.ncbi.nlm.nih.gov/books/NBK488189/

• Allelic: Deafness, AD 65 (TBC1D24)
• Allelic: Deafness, Ar 86 (TBC1D24)
• Allelic: Epilepsy, childhood absence, susceptibility to, 4 (GABRA2)
• Allelic: Epilepsy, idiopathic generalized, 10 (GABRD)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 9 (CACNB4)
• Allelic: Epilepsy, juvenile absence, susceptibility to, 1 (EFHC1)
• Allelic: Episodic ataxia, type 5 (CACNB4)
• Allelic: Farber lipogranulomatosis (ASAH1)
• Allelic: Generalized epilepsy with febrile seizures plus, type 5, susceptibility to (GABRD)
• Allelic: Lipodystrophy, partial, acquired, susceptibility to (LMNB2)
• Cherry red spot-myoclonus syndrome (NEU1)
• DOORS [deafness, onychodystrophy, osteodystrophy, mental retardation, seizures] syndrome (TBC1D24)
• Epilepsy, familial adult myoclonic, 2 (STARD7)
• Epilepsy, juvenile myoclonic, susceptibility to (GABRD)
• Epilepsy, juvenile myoclonic, susceptibility to, 5 (GABRA2)
• Epilepsy, juvenile myoclonic, susceptibility to, 6 (CACNB4)
• Epilepsy, progressive myoclonic 1A, Unverricht/Lundborg (AMT, CSTB)
• Epilepsy, progressive myoclonic 1B (PRICKLE1)
• Epilepsy, progressive myoclonic 2A, Lafora (EPM2A)
• Epilepsy, progressive myoclonic 2B, Lafora (NHLRC1)
• Epilepsy, progressive myoclonic 3, with/-out intracellular inclusions (KCTD7)
• Epilepsy, progressive myoclonic 4, with or without renal failure (SCARB2)
• Epilepsy, progressive myoclonic 6 (GOSR2)
• Epilepsy, progressive myoclonic 7 (KCNC1)
• Epilepsy, progressive myoclonic, 10 (PRDM8)
• Epilepsy, progressive myoclonic, 11 (SEMA6B)
• Epilepsy, progressive myoclonic, 8 (CERS1)
• Epilepsy, progressive myoclonic, 9 (LMNB2)
• Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp (TBC1D24)
• Epileptic encephalopathy, early infantile, 16 (TBC1D24)
• Epileptic encephalopathy, early infantile, 19 (GABRA2)
• Epileptic encephalopathy, early infantile, 67 (CUX2)
• Glycine encephalopathy (GLDC)
• Infantile onset myoclonic epileptic encephalopathy (CUX2)
• Lipomucopolysaccharidosis (NEU1)
• Mucolipidosis I (NEU1)
• Myoclonic atonic seizures [panelapp] (SYNCRIP)
• Myoclonic epilepsy + intellectual disability [panelapp] (CSNK2B)
• Myoclonic epilepsy, infantile, familial (TBC1D24)
• Myoclonic epilepsy, juvenile, susceptibility to, 1 (EFHC1)
• Myoclonic seizures [panelapp] (GRIA2)
• Myoclonic-atonic epilepsy (SLC6A1)
• Neurodevelopmental disorder with language impairment and behavioral abnormalities (GRIA2)
• Poirier-Bienvenu neurodevelopmental syndrome: early-onset seizures + ID (CSNK2B)
• Sandhoff disease, infantile, juvenile + adult forms (HEXB)
• Sialidosis, type I-II (NEU1)
• Spinal muscular atrophy with progressive myoclonic epilepsy (ASAH1)