Journal of Pediatric Neurology
DOI: 10.1055/s-0041-1728645
Review Article

TBC1D24 and Its Related Epileptic Encephalopathy

Tiziana Timpanaro*
1   Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Flavia La Mendola*
4   Unit of Pediatrics, Caltanissetta Hospital, Caltanissetta, Italy
,
Sebastiano Billone
2   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Alessandra Di Nora
2   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Ausilia Collotta
2   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Alessandra Sauna
2   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Stefania Salafia
3   Unit of Pediatrics, Lentini Hospital, Lentini, Italy
,
Raffaele Falsaperla
5   Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
6   Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
› Author Affiliations

Abstract

TBC1D24, mapped to 16p13.3, encodes a protein containing a Tre2/Bub2/Cdc16 (TBC) domain, belonging to the super-family of Rab GTPase activating proteins (Rab-GAP). These proteins regulate various functions, including the regulation of the traffic of the vesicular membrane. Several TBC1D24 mutations have been related to autosomal recessive neurological disorders, including severe developmental encephalopathies with malignant early childhood epilepsy, benign epilepsy, epileptic encephalopathy, and a complex neurological syndrome characterized by deafness, onychodystrophy, bone and neurological degeneration. Mutations of TBC1D24 have also been reported in patients with nonsyndromic deafness with dominant or recessive inheritance. Mechanisms underlying TBC1D24-associated disorders and the functions of TBC1D24 products in the generation of such complex spectrum of diseases remain partly unclear and future studies are needed to clarify this aspect, in order to improve the management of seizures and for the prevention of complication (including death) of newly diagnosed patients affected by TBC1D24-related disorders.

* Both the authors contributed equally to the present article.




Publication History

Received: 01 September 2020

Accepted: 23 February 2021

Article published online:
21 May 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Falace A, Filipello F, La Padula V. et al. TBC1D24, an ARF6-interacting protein, is mutated in familial infantile myoclonic epilepsy. Am J Hum Genet 2010; 87 (03) 365-370
  • 2 Campeau PM, Hennekam RC. DOORS syndrome collaborative group. DOORS syndrome: phenotype, genotype and comparison with Coffin-Siris syndrome. Am J Med Genet C Semin Med Genet 2014; 166C (03) 327-332
  • 3 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: First descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes. Am J Med Genet A 2018; 176 (03) 515-550
  • 4 Ruggieri M, Praticò AD, Serra A. et al. Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms. Childs Nerv Syst 2017; 33 (04) 549-560
  • 5 Ruggieri M, Praticò AD, Caltabiano R, Polizzi A. Rediagnosing one of Smith's patients (John McCann) with “neuromas tumours” (1849). Neurol Sci 2017; 38 (03) 493-499
  • 6 Ruggieri M, Praticò AD, Scuderi A, Sorge G, Polizzi A. The multiple faces of artwork diagnoses. Lancet Neurol 2017; 16 (06) 417-418
  • 7 Pan X, Eathiraj S, Munson M, Lambright DG. TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. Nature 2006; 442 (7100): 303-306
  • 8 Ranieri C, Di Tommaso S, Loconte DC. et al. In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS). Neurogenetics 2018; 19 (02) 77-91
  • 9 Pavone P, Praticò AD, Falsaperla R. et al. Congenital generalized hypertrichosis: the skin as a clue to complex malformation syndromes. Ital J Pediatr 2015; 41: 55
  • 10 Falace A, Buhler E, Fadda M. et al. TBC1D24 regulates neuronal migration and maturation through modulation of the ARF6-dependent pathway. Proc Natl Acad Sci U S A 2014; 111 (06) 2337-2342
  • 11 Pavone P, Briuglia S, Falsaperla R. et al. Wide spectrum of congenital anomalies including choanal atresia, malformed extremities, and brain and spinal malformations in a girl with a de novo 5.6-Mb deletion of 13q12.11-13q12.13. Am J Med Genet A 2014; 164A (07) 1734-1743
  • 12 Uytterhoeven V, Kuenen S, Kasprowicz J, Miskiewicz K, Verstreken P. Loss of skywalker reveals synaptic endosomes as sorting stations for synaptic vesicle proteins. Cell 2011; 145 (01) 117-132
  • 13 Campeau PM, Kasperaviciute D, Lu JT. et al. The genetic basis of DOORS syndrome: an exome-sequencing study. Lancet Neurol 2014; 13 (01) 44-58
  • 14 Chesneau L, Dambournet D, Machicoane M. et al. An ARF6/Rab35 GTPase cascade for endocytic recycling and successful cytokinesis. Curr Biol 2012; 22 (02) 147-153
  • 15 Chaineau M, Ioannou MS, McPherson PS. Rab35: GEFs, GAPs and effectors. Traffic 2013; 14 (11) 1109-1117
  • 16 Pavone P, Praticò AD, Gentile G. et al. A neurocutaneous phenotype with paired hypo- and hyperpigmented macules, microcephaly and stunted growth as prominent features. Eur J Med Genet 2016; 59 (05) 283-289
  • 17 Fernandes AC, Uytterhoeven V, Kuenen S. et al. Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration. J Cell Biol 2014; 207 (04) 453-462
  • 18 Cremona O, Di Paolo G, Wenk MR. et al. Essential role of phosphoinositide metabolism in synaptic vesicle recycling. Cell 1999; 99 (02) 179-188
  • 19 Verstreken P, Koh TW, Schulze KL. et al. Synaptojanin is recruited by endophilin to promote synaptic vesicle uncoating. Neuron 2003; 40 (04) 733-748
  • 20 Finelli MJ, Aprile D, Castroflorio E. et al. The epilepsy-associated protein TBC1D24 is required for normal development, survival and vesicle trafficking in mammalian neurons. Hum Mol Genet 2019; 28 (04) 584-597
  • 21 Milh M, Falace A, Villeneuve N. et al. Novel compound heterozygous mutations in TBC1D24 cause familial malignant migrating partial seizures of infancy. Hum Mutat 2013; 34 (06) 869-872
  • 22 Pavone P, Rizzo R, Conti I. et al. Primary headaches in children: clinical findings on the association with other conditions. Int J Immunopathol Pharmacol 2012; 25 (04) 1083-1091
  • 23 Falsaperla R, Praticò AD, Ruggieri M. et al. Congenital muscular dystrophy: from muscle to brain. Ital J Pediatr 2016; 42 (01) 78
  • 24 Aprile D, Fruscione F, Baldassari S. et al. TBC1D24 regulates axonal outgrowth and membrane trafficking at the growth cone in rodent and human neurons. Cell Death Differ 2019; 26 (11) 2464-2478
  • 25 Afawi Z, Mandelstam S, Korczyn AD. et al. TBC1D24 mutation associated with focal epilepsy, cognitive impairment and a distinctive cerebro-cerebellar malformation. Epilepsy Res 2013; 105 (1-2): 240-244
  • 26 Yoon J, Hwang YS, Lee M. et al. TBC1d24-ephrinB2 interaction regulates contact inhibition of locomotion in neural crest cell migration. Nat Commun 2018; 9 (01) 3491
  • 27 Guven A, Tolun A. TBC1D24 truncating mutation resulting in severe neurodegeneration. J Med Genet 2013; 50 (03) 199-202
  • 28 Muona M, Berkovic SF, Dibbens LM. et al. A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy. Nat Genet 2015; 47 (01) 39-46
  • 29 Barbagallo M, Ruggieri M, Incorpora G. et al. Infantile spasms in the setting of Sturge-Weber syndrome. Childs Nerv Syst 2009; 25 (01) 111-118
  • 30 Balestrini S, Milh M, Castiglioni C. et al. TBC1D24 genotype-phenotype correlation: epilepsies and other neurologic features. Neurology 2016; 87 (01) 77-85
  • 31 Dunckelmann RJ, Ebinger F, Schulze A, Wanders RJ, Rating D, Mayatepek E. 2-ketoglutarate dehydrogenase deficiency with intermittent 2-ketoglutaric aciduria. Neuropediatrics 2000; 31 (01) 35-38
  • 32 Pavone P, Falsaperla R, Ruggieri M. et al. Clinical course of N-Methyl-D-aspartate receptor encephalitis and the effectiveness of cyclophosphamide treatment. J Pediatr Neurol 2017; 15: 84-89
  • 33 Ruggieri M, Polizzi A, Marceca GP, Catanzaro S, Praticò AD, Di Rocco C. Introduction to phacomatoses (neurocutaneous disorders) in childhood. Childs Nerv Syst 2020; 36 (10) 2229-2268
  • 34 Pavone P, Falsaperla R, Ruggieri M, Praticò AD, Pavone L. West syndrome treatment: new roads for an old syndrome. Front Neurol 2013; 4: 113
  • 35 Berg AT, Berkovic SF, Brodie MJ. et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010; 51 (04) 676-685
  • 36 de Falco FA, Majello L, Santangelo R, Stabile M, Bricarelli FD, Zara F. Familial infantile myoclonic epilepsy: clinical features in a large kindred with autosomal recessive inheritance. Epilepsia 2001; 42 (12) 1541-1548
  • 37 Duru N, Iseri SA, Selçuk N, Tolun A. Early-onset progressive myoclonic epilepsy with dystonia mapping to 16pter-p13.3. J Neurogenet 2010; 24 (04) 207-215
  • 38 Rehman AU, Santos-Cortez RL, Morell RJ. et al; University of Washington Center for Mendelian Genomics. Mutations in TBC1D24, a gene associated with epilepsy, also cause nonsyndromic deafness DFNB86. Am J Hum Genet 2014; 94 (01) 144-152
  • 39 Tona R, Chen W, Nakano Y. et al. The phenotypic landscape of a Tbc1d24 mutant mouse includes convulsive seizures resembling human early infantile epileptic encephalopathy. Hum Mol Genet 2019; 28 (09) 1530-1547
  • 40 Duman D, Tekin M. Autosomal recessive nonsyndromic deafness genes: a review. Front Biosci 2012; 17: 2213-2236
  • 41 Falsaperla R, Perciavalle V, Pavone P. et al. Unilateral eye blinking arising from the ictal ipsilateral occipital area. Clin EEG Neurosci 2016; 47 (03) 243-246
  • 42 Incorpora G, Pavone P, Castellano-Chiodo D, Praticò AD, Ruggieri M, Pavone L. Gelastic seizures due to hypothalamic hamartoma: rapid resolution after endoscopic tumor disconnection. Neurocase 2013; 19 (05) 458-461
  • 43 Pavone P, Praticò AD, Pavone V. et al. Ataxia in children: early recognition and clinical evaluation. Ital J Pediatr 2017; 43 (01) 6
  • 44 Mucha BE, Hennekam RCM, Sisodiya S, Campeau PM. TBC1D24-Related Disorders. 2015 Feb 26. In: Adam MP, Ardinger HH, Pagon RA. eds. GeneReviews®. Seattle, WA: University of Washington; 1993-2020
  • 45 Pavone V, Signorelli SS, Praticò AD. et al. Total hemi-overgrowth in pigmentary mosaicism of the (hypomelanosis of) Ito type: eight case reports. Medicine (Baltimore) 2016; 95 (10) e2705
  • 46 Azaiez H, Booth KT, Bu F. et al. TBC1D24 mutation causes autosomal-dominant nonsyndromic hearing loss. Hum Mutat 2014; 35 (07) 819-823
  • 47 Zhang L, Hu L, Chai Y, Pang X, Yang T, Wu H. A dominant mutation in the stereocilia-expressing gene TBC1D24 is a probable cause for nonsyndromic hearing impairment. Hum Mutat 2014; 35 (07) 814-818
  • 48 Ragona F, Castellotti B, Salis B. et al. Alternating hemiplegia and epilepsia partialis continua: a new phenotype for a novel compound TBC1D24 mutation. Seizure 2017; 47: 71-73
  • 49 Corbett MA, Bahlo M, Jolly L. et al. A focal epilepsy and intellectual disability syndrome is due to a mutation in TBC1D24. Am J Hum Genet 2010; 87 (03) 371-375
  • 50 Banuelos E, Ramsey K, Belnap N. et al. Case report: novel mutations in TBC1D24 are associated with autosomal dominant tonic-clonic and myoclonic epilepsy and recessive Parkinsonism, psychosis, and intellectual disability. F1000 Res 2017; 6: 553
  • 51 Lüthy K, Mei D, Fischer B. et al. TBC1D24-TLDc-related epilepsy exercise-induced dystonia: rescue by antioxidants in a disease model. Brain 2019; 142 (08) 2319-2335
  • 52 Pavone P, Praticò AD, Ruggieri M. et al. Acquired peripheral neuropathy: a report on 20 children. Int J Immunopathol Pharmacol 2012; 25 (02) 513-517
  • 53 Stražišar BG, Neubauer D, Paro Panjan D, Writzl K. Early-onset epileptic encephalopathy with hearing loss in two siblings with TBC1D24 recessive mutations. Eur J Paediatr Neurol 2015; 19 (02) 251-256
  • 54 Ruggieri M, Milone P, Pavone P. et al. Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients. Am J Med Genet A 2012; 158A (11) 2870-2880
  • 55 Ruggieri M, Iannetti P, Pavone L. Delineation of a newly recognized neurocutaneous malformation syndrome with “cutis tricolor”. Am J Med Genet A 2003; 120A (01) 110-116
  • 56 Pavone P, Praticò AD, Vitaliti G. et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
  • 57 Ruggieri M, Praticò AD, Serra A. et al. Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Acta Otorhinolaryngol Ital 2016; 36 (05) 345-367
  • 58 Polizzi A, Finocchiaro M, Parano E, Pavone P, Musumeci S, Polizzi A. Recurrent peripheral neuropathy in a girl with celiac disease. J Neurol Neurosurg Psychiatry 2000; 68 (01) 104-105
  • 59 Vincent A, Jacobson L, Plested P. et al. Antibodies affecting ion channel function in acquired neuromyotonia, in seropositive and seronegative myasthenia gravis, and in antibody-mediated arthrogryposis multiplex congenita. Ann N Y Acad Sci 1998; 841: 482-496
  • 60 Polizzi A, Pavone P, Ciancio E, La Rosa C, Sorge G, Ruggieri M. Hypertrichosis cubiti (hairy elbow syndrome): a clue to a malformation syndrome. J Pediatr Endocrinol Metab 2005; 18 (10) 1019-1025
  • 61 Polizzi A, Pavone P, Parano E, Incorpora G, Ruggieri M. Lack of progression of brain atrophy in Aicardi-Goutières syndrome. Pediatr Neurol 2001; 24 (04) 300-302
  • 62 Polizzi A, Coghill S, McShane MA, Squier W. Acute ataxia complicating Langherans cell histiocytosis. Arch Dis Child 2002; 86 (02) 130-131
  • 63 Caltabiano R, Magro G, Polizzi A. et al. A mosaic pattern of INI1/SMARCB1 protein expression distinguishes Schwannomatosis and NF2-associated peripheral schwannomas from solitary peripheral schwannomas and NF2-associated vestibular schwannomas. Childs Nerv Syst 2017; 33 (06) 933-940
  • 64 Praticò AD, Falsaperla R, Ruggieri M, Corsello G, Pavone P. Prognostic challenges of SCN1A genetic mutations: report on two children with mild features. J Pediatr Neurol 2016; 14: 82-88
  • 65 Praticò AD, Pavone P, Scuderi MG. et al. Symptomatic hypocalcemia in an epileptic child treated with valproic acid plus lamotrigine: a case report. Cases J 2009; 2: 7394
  • 66 Pratico AD, Longo L, Mansueto S. et al. Off-label use of drugs and adverse drug reactions in pediatric units: a prospective, multicenter study. Curr Drug Saf 2018; 13 (03) 200-207
  • 67 Pratico AD, Ruggieri M, Falsaperla R, Pavone P. A probable topiramate-induced limbs paraesthesia and rigid fingers flexion. Curr Drug Saf 2018; 13 (02) 131-136
  • 68 Falsaperla R, D'Angelo G, Praticò AD. et al. Ketogenic diet for infants with epilepsy: a literature review. Epilepsy Behav 2020; 112: 107361