Journal of Genetic Counseling

, Volume 21, Issue 4, pp 557–563 | Cite as

Genetic Counseling and Testing for FSHD (Facioscapulohumeral Muscular Dystrophy) in the Israeli Population

  • Miri Yanoov-Sharav
  • Esther Leshinsky-Silver
  • Sarit Cohen
  • Chana Vinkler
  • Marina Michelson
  • Tally Lerman-Sagie
  • Mira Ginzberg
  • Menahem Sadeh
  • Dorit Lev
Original Research

Abstract

Facioscapulohumeral muscular dystrophy (FSHD), is a dominantly inherited, late onset, progressive disease. At present, no treatment or prevention of symptoms are available. There is considerable clinical variability, even within families. The gene whose defect causes FSHD has not been identified, but molecular diagnosis can be made by analyzing D4Z4 repeat length on chromosome 4q35. The results can support or rule out the clinical diagnosis of FSHD, but there are also “gray zone”, non-conclusive results. During the years 2000–6, 66 individuals (including 7 asymptomatic individuals), were tested in our institute for D4Z4 repeat number. In 77% of the cases the results were conclusive: two thirds of them supported a diagnosis of FSHD while in a third this diagnosis was ruled out. In 23% the results were in the gray zone. Cognitive involvement was rare, occurring only when the D4Z4 repeat size was very small (<15 kb). Maximal utilization of the existing molecular test for FSHD demands detailed clinical and family pedigree information. We recommend that comprehensive genetic counseling always be given before and after molecular testing for FSHD, in addition to the neurological follow-up. Presymptomatic testing should only be offered when complete molecular evaluation can be offered, including 4qA and 4qB variant analysis.

Keywords

FSHD (Facioscapulohumeral Muscular Dystrophy) Genetic counseling Presymptomatic testing 

References

  1. Arahata, K., Ishihara, T., Fukunaga, H., Orimo, S., Lee, J. H., Goto, K., et al. (1995). Inflammatory response in facioscapulohumeral muscular dystrophy (FSHD): immunocytochemical and genetic analyses. Muscle & Nerve, 2, S56–S66.CrossRefGoogle Scholar
  2. Bakker, E., Van der Wielen, M. J. R., Voorhoeve, E., Ippel, P. F., Padberg, G. W., Frants, R. R., et al. (1996). Diagnostic, predictive, and prenatal testing for facioscapulohumeral muscular dystrophy: diagnostic approach for sporadic and familial cases. Journal of Medical Genetics, 33, 29–35.PubMedCrossRefGoogle Scholar
  3. Bird, T. D. (1999). Risks and benefits of DNA testing for neurogenetic disorders. Seminars in Neurology, 19, 253–259.PubMedCrossRefGoogle Scholar
  4. Brouwer, O. F., Padberg, G. W., Bakker, E., Wijmenga, C., & Frants, R. R. (1995). Early onset facioscapulohumeral muscular dystrophy. Muscle & Nerve, 2, S67–S72.CrossRefGoogle Scholar
  5. Butz, M., Koch, M. C., Müller-Felber, W., Lemmers, R. J., van der Maarel, S. M., & Schreiber, H. (2003). Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers. Journal of Neurology, 250(8), 932–937.PubMedCrossRefGoogle Scholar
  6. Dorobek, M., & Kabzińska, D. (2004). A severe case of facioscapulohumeral muscular dystrophy (FSHD) with some uncommon clinical features and a short 4q35 fragment. European Journal of Paediatric Neurology, 8(6), 313–316.PubMedCrossRefGoogle Scholar
  7. Flanigan, K. M., Coffeen, C. M., Sexton, L., Stauffer, D., Brunner, S., & Leppert, M. F. (2001). Genetic characterization of a large, historically significant Utah kindred with facioscapulohumeral dystrophy. Neuromuscular Disorders, 11(6–7), 525–529.PubMedCrossRefGoogle Scholar
  8. Funakoshi, M., Goto, K., & Arahata, K. (1998). Epilepsy and mental retardation in a subset of early onset 4q35-facioscapulohumeral muscular dystrophy. Neurology, 50(6), 1791–1794.PubMedCrossRefGoogle Scholar
  9. Harper, J. C., Delhanty, J. D., & Handyside, A. H. (2001). Preimplantation genetic diagnosis. West Sussex: John Wiley and Sons.CrossRefGoogle Scholar
  10. Kakourou, G., Dhanjal, S., Mamas, T., Gotts, S., Doshi, A., Fordham, K., et al. (2008). Preimplantation genetic diagnosis for myotonic dystrophy type 1 in the UK. Neuromuscular Disorders, 18(2), 131–136.PubMedCrossRefGoogle Scholar
  11. Kissel, J. T. (1999). Facioscapulohumeral dystrophy. Seminars in Neurology, 19(1), 35–43.PubMedCrossRefGoogle Scholar
  12. Klinge, L., Eagle, M., Haggerty, I. D., Roberts, C. E., Straub, V., & Bushby, K. M. (2006). Severe phenotype in infantile facioscapulohumeral muscular dystrophy. Neuromuscular Disorders, 16(9–10), 553–558.PubMedCrossRefGoogle Scholar
  13. Krasnianski, M., Neudecker, S., Eger, K., Jakubiczka, S., & Zierz, S. (2003). Typical facioscapulohumeral dystrophy phenotype in patients without FSHD 4q35 deletion. Journal of Neurology, 250(9), 1084–1087.PubMedCrossRefGoogle Scholar
  14. Lemmers, R. J., Osborn, M., Haaf, T., Rogers, M., Frants, R. R., Padberg, G. W., et al. (2003). D4F104S1 deletion in facioscapulohumeral muscular dystrophy: phenotype, size, and detection. Neurology, 61(2), 178–183.PubMedCrossRefGoogle Scholar
  15. Lemmers, R. J., van der Wielen, M. J., Bakker, E., Padberg, G. W., Frants, R. R., & van der Maarel, S. M. (2004). Somatic mosaicism in FSHD often goes undetected. Annals of Neurology, 55(6), 845–850.PubMedCrossRefGoogle Scholar
  16. Lemmers, R. J., Wohlgemuth, M., van der Gaag, K. J., van der Vliet, P. J., van Teijlingen, C. M., de Knijff, P., et al. (2007). Specific sequence variations within the 4q35 region are associated with facioscapulohumeral muscular dystrophy. American Journal of Human Genetics, 81(5), 884–894.PubMedCrossRefGoogle Scholar
  17. Lunt, P. W., & Harper, P. S. (1991). Genetic counselling in facioscapulohumeral muscular dystrophy. Journal of Medical Genetics, 28(10), 655–664.PubMedCrossRefGoogle Scholar
  18. Malcov, M., Ben-Yosef, D., Schwartz, T., Mey-Raz, N., Azem, F., Lessing, J. B., et al. (2005). Preimplantation genetic diagnosis (PGD) for Duchenne muscular dystrophy (DMD) by triplex-nested PCR. Prenatal Diagnosis, 25(13), 1200–1205.PubMedCrossRefGoogle Scholar
  19. Miura, K., Kumagai, T., Matsumoto, A., Iriyama, E., Watanabe, K., Goto, K., et al. (1998). Two cases of chromosome 4q35-linked early onset facioscapulohumeral muscular dystrophy with mental retardation and epilepsy. Neuropediatrics, 29(5), 239–241.PubMedCrossRefGoogle Scholar
  20. Podnar, S., & Zidar, J. (2006). Sensitivity of motor unit potential analysis in facioscapulohumeral muscular dystrophy. Muscle & Nerve, 34(4), 451–456.CrossRefGoogle Scholar
  21. Sacconi, S., Salviati, L., Bourget, I., Figarella, D., Péréon, Y., Lemmers, R., et al. (2006). Diagnostic challenges in facioscapulohumeral muscular dystrophy. Neurology, 24;67(8), 1464–1466.Google Scholar
  22. Saito, Y., Miyashita, S., Yokoyama, A., Komaki, H., Seki, A., Maegaki, Y., et al. (2007). Facioscapulohumeral muscular dystrophy with severe mental retardation and epilepsy. Brain & Development, 29(4), 231–233.CrossRefGoogle Scholar
  23. Smith, C. O., Lipe, H. P., & Bird, T. D. (2004). Impact of presymptomatic genetic testing for hereditary ataxia and neuromuscular disorders. Archives of Neurology, 61(6), 875–880.PubMedCrossRefGoogle Scholar
  24. Tawil, R., & Van Der Maarel, S. M. (2006). Facioscapulohumeral muscular dystrophy. Muscle & Nerve, 34(1), 1–15.CrossRefGoogle Scholar
  25. Tawil, R., Forrester, J., Griggs, R. C., Mendell, J., Kissel, J., McDermott, M., et al. (1996). Evidence for anticipation and association of deletion size with severity infacioscapulohumeral muscular dystrophy. The FSH-DY Group. Annals of Neurology, 39(6), 744–748.PubMedCrossRefGoogle Scholar
  26. Tawil, R., Figlewicz, D. A., Griggs, R. C., & Weiffenbach, B. (1998). Facioscapulohumeral dystrophy: a distinct regional myopathy with a novel molecular pathogenesis. FSH Consortium. Ann Neurol, 43, 279–282.CrossRefGoogle Scholar
  27. Thomas, N. S., Wiseman, K., Spurlock, G., MacDonald, M., Ustek, D., & Upadhyaya, M. (2007). A large patient study confirming that facioscapulohumeral muscular dystrophy (FSHD) disease expression is almost exclusively associated with an FSHD locus located on a 4qA-defined 4qter subtelomere. Journal of Medical Genetics, 44(3), 215–218.PubMedCrossRefGoogle Scholar
  28. Tonini, M. M., Passos-Bueno, M. R., Cerqueira, A., Matioli, S. R., Pavanello, R., & Zatz, M. (2004). Asymptomatic carriers and gender differences in facioscapulohumeral muscular dystrophy (FSHD). Neuromuscular Disorders, 4(1), 33–38.CrossRefGoogle Scholar
  29. Trevisan, C. P., Pastorello, E., Ermani, M., Angelini, C., Tomelleri, G., Tonin, P., et al. (2008). Facioscapulohumeral muscular dystrophy: a multicenter study on hearing function. Audiology & Neuro-Otology, 13(1), 1–6.CrossRefGoogle Scholar
  30. Upadhyaya, M., MacDonald, M., & Ravine, D. (1999). Prenatal diagnosis for facioscapulohumeral muscular dystrophy (FSHD). Prenatal Diagnosis, 19(10), 959–965.PubMedCrossRefGoogle Scholar
  31. Wijmenga, C., Frants, R. R., Brouwer, O. F., Moerer, P., Weber, J. L., & Padberg, G. W. (1990). Location of facioscapulohumeral muscular dystrophy gene on chromosome 4. Lancet, 15;336(8716), 651–653.Google Scholar
  32. Wijmenga, C., Frants, R. R., Hewitt, J. E., van Deutekom, J. C., van Geel, M., Wright, T. J., et al. (1993). Molecular genetics of facioscapulohumeral muscular dystrophy. Neuromuscular Disorders, 3(5–6), 487–491.PubMedCrossRefGoogle Scholar
  33. Wu, Z. Y., Wang, Z. Q., Murong, S. X., & Wang, N. (2004). FSHD in Chinese population: characteristics of translocation and genotype-phenotype correlation. Neurology, 63(3), 581–583.PubMedCrossRefGoogle Scholar
  34. Zatz, M., Marie, S. K., Passos-Bueno, M. R., Vainzof, M., Campiotto, S., Cerqueira, A., et al. (1995). High proportion of new mutations and possible anticipation in Brazilian facioscapulohumeral muscular dystrophy families. American Journal of Human Genetics, 56(1), 99–105.PubMedGoogle Scholar
  35. Zatz, M., Marie, S. K., Cerqueira, A., Vainzof, M., Pavanello, R. C., & Passos-Bueno, M. R. (1998). The facioscapulohumeral muscular dystrophy (FSHD1) gene affects males more severely and more frequently than females. Am J Med Genet, 1;77(2), 155–161.Google Scholar

Copyright information

© National Society of Genetic Counselors, Inc. 2011

Authors and Affiliations

  • Miri Yanoov-Sharav
    • 1
    • 2
  • Esther Leshinsky-Silver
    • 2
    • 3
    • 5
  • Sarit Cohen
    • 3
  • Chana Vinkler
    • 1
    • 2
  • Marina Michelson
    • 1
    • 2
  • Tally Lerman-Sagie
    • 2
    • 5
  • Mira Ginzberg
    • 2
  • Menahem Sadeh
    • 4
    • 5
  • Dorit Lev
    • 1
    • 2
    • 5
  1. 1.Institute of Medical GeneticsWolfson Medical CenterHolonIsrael
  2. 2.Metabolic Neurogenetic ClinicWolfson Medical CenterHolonIsrael
  3. 3.Molecular Genetics LaboratoryWolfson Medical CenterHolonIsrael
  4. 4.Department of NeurologyWolfson Medical CenterHolonIsrael
  5. 5.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael

Personalised recommendations