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Journal of Neurology

, Volume 259, Issue 12, pp 2590–2598 | Cite as

A compound heterozygous missense mutation and a large deletion in the KCTD7 gene presenting as an opsoclonus-myoclonus ataxia-like syndrome

  • Lubov Blumkin
  • Sara Kivity
  • Dorit Lev
  • Sarit Cohen
  • Ruth Shomrat
  • Tally Lerman-Sagie
  • Esther Leshinsky-SilverEmail author
Original Communication
  • 599 Downloads

Abstract

Mutations in the potassium channel-related gene KCTD7 were described so far in a single family with progressive myoclonus epilepsy. We describe a unique phenotype: acute onset of myoclonus and ataxia, associated with abnormal opsoclonus-like eye movements; improvement of clinical symptoms under steroid treatment; and appearance of epileptic activity on EEG 2 years later without overt seizures. After excluding possible genetic causes, whole-genome exome sequencing was performed in order to identify the causative gene. One heterozygous missense mutation (R84W) was detected by exome sequencing and a large heterozygous deletion of exons 3 and 4 by MLPA analysis. The father is heterozygous for the R84W mutation and the mother is heterozygous for the exon 3+4 deletion. The mutation affects a highly conserved segment of the predicted protein, changing a basic amino acid into neutral. The large deletion probably results in a truncated protein. The different phenotype broadens the spectrum of KCTD7-related diseases. Therefore, patients diagnosed as having opsoclonus-myoclonus with an atypical course should be evaluated for KCTD7 mutations.

Keywords

Opsoclonus-myoclonus-ataxia Exomics KCTD7 Corticosteroid treatment 

Notes

Acknowledgments

We thank Prof. Pranzatelli MR from the National Pediatric Myoclonus Center, Southern Illinois University School of Medicine for his great help in the evaluation and treatment of our patient.

Conflicts of interest

None.

References

  1. 1.
    Kinsbourne M (1962) Myoclonic encephalopathy of infants. J Neurol Neurosurg Psychiat 25:271–276CrossRef
  2. 2.
    Pranzatelli MR, Chun KY, Moxness M, Tate ED, Allison TJ (2005) Cerebrospinal fluid ACTH and cortisol in opsoclonus-myoclonus: effect of therapy. Pediatr Neurol 33:121–126CrossRef
  3. 3.
    Ramachandran N, Girard JM, Turnbull J, Minassian BA (2009) The autosomal recessively inherited progressive myoclonus epilepsies and their genes. Epilepsia 50(Suppl 5):29–36CrossRef
  4. 4.
    Bassuk AG, Wallace RH, Buhr A, Buller AR, Afawi Z, Shimojo M, Miyata S, Chen S, Gonzalez-Alegre P, Griesbach HL, Wu S, Nashelsky M, Vladar EK, Antic D, Ferguson PJ, Cirak S, Voit T, Scott MP, Axelrod JD, Gurnett C, Daoud AS, Kivity S, Neufeld MY, Mazarib A, Straussberg R, Walid S, Korczyn AD, Slusarski DC, Berkovic SF, El-Shanti HI (2008) A homozygous mutation in human PRICKLE1 causes an autosomal-recessive progressive myoclonus epilepsy–ataxia syndrome. Am J Hum Genet 83:572–581CrossRef
  5. 5.
    Van Bogaert P, Azizieh R, Désir J, Aeby A, De Meirleir L, Laes JF, Christiaens F, Abramowicz MJ (2007) Mutation of a potassium channel-related gene in progressive myoclonic epilepsy. Ann Neurol 61:579–586CrossRef
  6. 6.
    Dibbens LM, Michelucci R, Gambardella A, Andermann F, Rubboli G, Bayly MA, Joensuu T, Vears DF, Franceschetti S, Canafoglia L, Wallace R, Bassuk AG, Power DA, Tassinari CA, Andermann E, Lehesjoki AE, Berkovic SF (2009) SCARB2 mutations in progressive myoclonus epilepsy (PME) without renal failure. Ann Neurol 66:532–536CrossRef
  7. 7.
    Pérez-Dueñas B, Toma C, Ormazábal A, Muchart J, Sanmartí F, Bombau G, Serrano M, García-Cazorla A, Cormand B, Artuch R (2010) Progressive ataxia and myoclonic epilepsy in a patient with a homozygous mutation in the FOLR1 gene. J Inherit Metab Dis 33:795–802CrossRef
  8. 8.
    Corbett MA, Schwake M, Bahlo M, Dibbens LM, Lin M, Gandolfo LC, Vears DF, O’Sullivan JD, Robertson T, Bayly MA, Gardner AE, Vlaar AM, Korenke GC, Bloem BR, de Coo IF, Verhagen JMA, Lehesjoki A-E, Gecz J, Berkovic SF (2011) A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia. Am J Hum Genet 88:657–663CrossRef
  9. 9.
    Matthay KK, Blaes F, Hero B, Plantaz D, De Alarcon P, Mitchell WG, Pike M, Pistoia V (2005) Opsoclonus myoclonus syndrome in neuroblastoma: a report from a workshop on the dancing eyes syndrome at the advances in neuroblastoma meeting in Genoa, Italy. Cancer Lett 228:275–282CrossRef
  10. 10.
    Pranzatelli MR, Travelstead AL, Tate ED, Allison TJ, Verhulst SJ (2004) CSF B-cell expansion in opsoclonus-myoclonus syndrome: a biomarker of disease activity. Mov Disord 19:770–777CrossRef
  11. 11.
    Gorman MP (2010) Update on diagnosis, treatment, and prognosis in opsoclonus-myoclonus-ataxia syndrome. Curr Opin Pediatr 22:745–750CrossRef
  12. 12.
    Shahwan A, Farrell M, Delanty N (2005) Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol 4:239–248CrossRef
  13. 13.
    Pranzatelli MR (1992) The neurobiology of the opsoclonus-myoclonus syndrome. Clin Neuropharmacol 15:186–228CrossRef
  14. 14.
    Haden SV, McShane MA, Holt CM (2009) Opsoclonus myoclonus: a non-epileptic movement disorder that may present as status epilepticus. Arch Dis Child 94:897–899CrossRef
  15. 15.
    Rubboli G, Franceschetti S, Berkovic SF, Canafoglia L, Gambardella A, Dibbens LM, Riguzzi P, Campieri C, Magaudda A, Tassinari CA, Michelucci R (2011) Clinical and neurophysiologic features of progressive myoclonus epilepsy without renal failure caused by SCA. Epilepsia 52:2356–2363CrossRef
  16. 16.
    Herman TE, Siegel MJ (2009) Ataxia without opsoclonus: right lumbar sympathetic trunk neuroblastoma. Clin Pediatr 48:336–340CrossRef
  17. 17.
    de Haan GJ, Pinto D, Carton D, Bader A, Witte J, Peters E, van Erp G, Vandereyken W, Boezeman E, Wapenaar MC, Boon P, Halley D, Koeleman BP, Lindhout D (2006) A novel splicing mutation in KCNQ2 in a multigenerational family with BFNC followed for 25 years. Epilepsia 47:851–889CrossRef
  18. 18.
    Blumkin L, Suls A, Deconinck T, De Jonghe P, Linder I, Kivity S, Dabby R, Leshinsky-Silver E, Lev D, Lerman-Sagie T (2011) Neonatal seizures associated with a severe neonatal myoclonus-like dyskinesia due to a familial KCNQ2 gene mutation. Eur J Paediatr Neurol.
  19. 19.
    Azizieh R, Orduz D, Van Bogaert P, Bouschet T, Rodriguez W, Schiffmann SN, Pirson I, Abramowicz MJ (2011) Progressive myoclonic epilepsy-associated gene KCTD7 is a regulator of potassium conductance in neurons. Mol Neurobiol 44:111–121CrossRef

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Lubov Blumkin
    • 1
    • 2
  • Sara Kivity
    • 1
    • 2
  • Dorit Lev
    • 2
    • 3
    • 6
  • Sarit Cohen
    • 5
  • Ruth Shomrat
    • 4
  • Tally Lerman-Sagie
    • 1
    • 2
    • 6
  • Esther Leshinsky-Silver
    • 2
    • 5
    • 6
    Email author
  1. 1.Pediatric NeurologyWolfson Medical CenterHolonIsrael
  2. 2.Metabolic Neurogenetic ClinicWolfson Medical CenterHolonIsrael
  3. 3.Genetics InstituteWolfson Medical CenterHolonIsrael
  4. 4.Pronto Diagnostics, LtdTel AvivIsrael
  5. 5.Molecular Genetic LaboratoryWolfson Medical CenterHolonIsrael
  6. 6.Sackler Medical SchoolTel Aviv UniversityTel AvivIsrael

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