Top

Published in:

01-07-2010 | Original Communication

Facioscapulohumeral muscular dystrophy presenting with unusual phenotypes and atypical morphological features of vacuolar myopathy

Authors: Peter Reilich, Nicolai Schramm, Benedikt Schoser, Peter Schneiderat, Nicola Strigl-Pill, Josef Müller-Höcker, Wolfram Kress, Andreas Ferbert, Sabine Rudnik-Schöneborn, Johannes Noth, Hanns Lochmüller, Joachim Weis, Maggie C. Walter

Published in: Journal of Neurology | Issue 7/2010

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common muscular dystrophy and usually follows an autosomal dominant trait. Clinically, FSHD affects facial muscles and proximal upper limb and girdle muscles, but may present with variable clinical phenotypes even within the same family. Most genetically confirmed FSHD patients exhibit unspecific morphological signs of a degenerative myopathy. We report on five unrelated patients who carried the pathogenic FSHD mutation on chromosome 4q35. Muscle biopsies revealed numerous rimmed vacuoles and filamentous cytoplasmic inclusions in all cases. Clinically, the patients suffered from weakness and atrophy predominantly of the lower limb muscles. In conclusion, we suggest considering FSHD in the differential diagnosis of adult-onset distal myopathies with rimmed vacuoles.

Askanas V, Engel WK (2008) Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer’s and Parkinson’s disease brains. Acta Neuropathol 116:583–595CrossRefPubMed

Awerbuch GI, Nigro MA, Wishnow R (1990) Beevor’s sign and facioscapulohumeral dystrophy. Arch Neurol 47:1208–1209PubMed

Busse K, Kohler J, Stegmann K, Pongratz D, Koch MC, Schreiber H (2000) An inherited 4q35-EcoRI-DNA-fragment of 35 kb in a family with a sporadic case of facioscapulohumeral muscular dystrophy (FSHD). Neuromuscul Disord 10:178–181CrossRefPubMed

Butz M, Koch MC, Muller-Felber W, Lemmers RJ, van der Maarel SM, Schreiber H (2003) Facioscapulohumeral muscular dystrophy. Phenotype-genotype correlation in patients with borderline D4Z4 repeat numbers. J Neurol 250:932–937CrossRefPubMed

Eger K, Jordan B, Habermann S, Zierz S (2009) Beevor’s sign in facioscapulohumeral muscular dystrophy: an old sign with new implications. J Neurol. doi:10.1007/s00415-009-5342-9

Felice KJ, Jones JM, Conway SR (2005) Facioscapulohumeral dystrophy presenting as infantile facial diplegia and late-onset limb-girdle myopathy in members of the same family. Muscle Nerve 32:368–372CrossRefPubMed

Felice KJ, Moore SA (2001) Unusual clinical presentations in patients harboring the facioscapulohumeral dystrophy 4q35 deletion. Muscle Nerve 24:352–356CrossRefPubMed

Felice KJ, North WA, Moore SA, Mathews KD (2000) FSH dystrophy 4q35 deletion in patients presenting with facial-sparing scapular myopathy. Neurology 54:1927–1931PubMed

Fidzianska A, Glinka Z, Kaminska A, Niebroj-Dobosz I (2008) Altered distribution of lamin and emerin in muscle nuclei of sIBM patients. Clin Neuropathol 27:424–429PubMed

10.

Figarella-Branger D, Pellissier JF, Serratrice G, Pouget J, Bianco N (1989) Immunocytochemical study of the inflammatory forms of facioscapulohumeral myopathies and correlation with other types of myositis. Ann Pathol 9:100–108PubMed

11.

Finsterer J, Stollberger C, Meng G (2005) Cardiac involvement in facioscapulohumeral muscular dystrophy. Cardiology 103:81–83CrossRefPubMed

12.

Flanigan KM (2003) Facioscapulohumeral muscular dystrophy and scapulohumeral syndrome. In: Engel AG, Franzini-Armstrong C (eds) Myology. McGraw-Hill, New York, pp 1123–1134

13.

Funakoshi M, Goto K, Arahata K (1998) Epilepsy and mental retardation in a subset of early onset 4q35-facioscapulohumeral muscular dystrophy. Neurology 50:1791–1794PubMed

14.

Gabellini D, D’Antona G, Moggio M, Prelle A, Zecca C, Adami R, Angeletti B, Ciscato P, Pellegrino MA, Bottinelli R, Green MR, Tupler R (2006) Facioscapulohumeral muscular dystrophy in mice overexpressing FRG1. Nature 439:973–977PubMed

15.

Galluzzi G, Deidda G, Cacurri S, Colantoni L, Piazzo N, Vigneti E, Ricci E, Servidei S, Merico B, Pachi A, Brambati B, Mangiola F, Tonali P, Felicetti L (1999) Molecular analysis of 4q35 rearrangements in fascioscapulohumeral muscular dystrophy (FSHD): application to family studies for a correct genetic advice and a reliable prenatal diagnosis of the disease. Neuromuscul Disord 9:190–198CrossRefPubMed

16.

Hauser MA, Horrigan SK, Salmikangas P, Torian UM, Viles KD, Dancel R, Tim RW, Taivainen A, Bartoloni L, Gilchrist JM, Stajich JM, Gaskell PC, Gilbert JR, Vance JM, Pericak-Vance MA, Carpen O, Westbrook CA, Speer MC (2000) Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet 9:2141–2147CrossRefPubMed

17.

Jardine PE, Upadhyaya M, Maynard J, Harper P, Lunt PW (1994) A scapular onset muscular dystrophy without facial involvement: possible allelism with facioscapulohumeral muscular dystrophy. Neuromuscul Disord 4:477–482CrossRefPubMed

18.

Krasnianski M, Eger K, Neudecker S, Jakubiczka S, Zierz S (2003) Atypical phenotypes in patients with facioscapulohumeral muscular dystrophy 4q35 deletion. Arch Neurol 60:1421–1425CrossRefPubMed

19.

Krasnianski M, Neudecker S, Eger K, Schulte-Mattler W, Zierz S (2003) Facioscapulohumeral muscular dystrophy. The spectrum of clinical manifestations and molecular genetic changes. Nervenarzt 74:151–158CrossRefPubMed

20.

Krause S, Gohringer T, Walter MC, Schoser BG, Reilich P, Linn J, Popperl GE, Frolich L, Hentschel F, Lochmuller H, Danek A (2007) Brain imaging and neuropsychology in late-onset dementia due to a novel mutation (R93C) of valosin-containing protein. Clin Neuropathol 26:232–240PubMed

21.

Landouzy L, Déjerine J (1884) De la myopathie atrophique progressive (myopathie héréditaire débutant dans l’enfance, par la face sans altération du système nerveux). C R Seances Acad Sci 98:53–58

22.

Lemmers RJ, Wohlgemuth M, Frants RR, Padberg GW, Morava E, van der Maarel SM (2004) Contractions of D4Z4 on 4qB subtelomeres do not cause facioscapulohumeral muscular dystrophy. Am J Hum Genet 75:1124–1130CrossRefPubMed

23.

Lunt PW, Harper PS (1991) Genetic counselling in facioscapulohumeral muscular dystrophy. J Med Genet 28:655–664CrossRefPubMed

24.

Molnar M, Dioszeghy P, Mechler F (1991) Inflammatory changes in facioscapulohumeral muscular dystrophy. Eur Arch Psychiatry Clin Neurosci 241:105–108CrossRefPubMed

25.

Moreira ES, Wiltshire TJ, Faulkner G, Nilforoushan A, Vainzof M, Suzuki OT, Valle G, Reeves R, Zatz M, Passos-Bueno MR, Jenne DE (2000) Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 24:163–166CrossRefPubMed

26.

Munsat TL (1994) Facioscapulohumeal disease and the scapuloperoneal syndrome. In: Engel AG, Franzini-Armstrong C (eds) Myology. McGraw-Hill, New York, pp 1220–1232

27.

Neudecker S, Krasnianski M, Bahn E, Zierz S (2004) Rimmed vacuoles in facioscapulohumeral muscular dystrophy: a unique ultrastructural feature. Acta Neuropathol (Berl) 108:257–259CrossRef

28.

Olsen DB, Gideon P, Jeppesen TD, Vissing J (2006) Leg muscle involvement in facioscapulohumeral muscular dystrophy assessed by MRI. J Neurol 253:1437–1441CrossRefPubMed

29.

Osborne RJ, Welle S, Venance SL, Thornton CA, Tawil R (2006) Expression profile of FSHD supports a link between retinal vasculopathy and muscular dystrophy. Neurology 68:569–577CrossRefPubMed

30.

Padberg GW (1982) Facioscapulohumeral disease. University of Leiden, Leiden, pp 23–24 (see also pp 133–134)

31.

Padberg GW, Lunt PW, Koch M, Fardeau M (1991) Diagnostic criteria for facioscapulohumeral muscular dystrophy. Neuromuscul Disord 1:231–234CrossRefPubMed

32.

Pradhan S (2002) Poly-Hill sign in facioscapulohumeral dystrophy. Muscle Nerve 25:754–755CrossRefPubMed

33.

Reilich P, Petersen J, Vielhaber S, Mawrin C, Schneider-Gold C, Sommer C, Reiners KH, Deschauer M, Pongratz D, Lochmüller H, Walter MC (2006) LGMD 2I due to the common mutation 826C>A in the FKRP gene presenting as myopathy with vacuoles and paired-helical filaments. Acta Myol 25:73–76PubMed

34.

Rudnik-Schoneborn S, Weis J, Kress W, Hausler M, Zerres K (2008) Becker’s muscular dystrophy aggravating facioscapulohumeral muscular dystrophy—double trouble as an explanation for an atypical phenotype. Neuromuscul Disord 18:881–885CrossRefPubMed

35.

Sacconi S, Salviati L, Bourget I, Figarella D, Pereon Y, Lemmers R, van der Maarel S, Desnuelle C (2006) Diagnostic challenges in facioscapulohumeral muscular dystrophy. Neurology 67:1464–1466CrossRefPubMed

36.

Schoser B (2009) Physiology, pathophysiology and diagnostic significance of autophagic changes in skeletal muscle tissue—towards the enigma of rimmed and round vacuoles. Clin Neuropathol 28:59–70PubMed

37.

Schroder JM, Hoheneck M, Weis J, Deist H (1985) Ethylene oxide polyneuropathy: clinical follow-up study with morphometric and electron microscopic findings in a sural nerve biopsy. J Neurol 232:83–90CrossRefPubMed

38.

Shahrizaila N, Wills AJ (2005) Significance of Beevor’s sign in facioscapulohumeral dystrophy and other neuromuscular diseases. J Neurol Neurosurg Psychiatry 76:869–870CrossRefPubMed

39.

Slipetz DM, Aprille JR, Goodyer PR, Rozen R (1991) Deficiency of complex III of the mitochondrial respiratory chain in a patient with facioscapulohumeral disease. Am J Hum Genet 48:502–510PubMed

40.

Thomas NS, 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. J Med Genet 44:215–218CrossRefPubMed

41.

Trevisan CP, Pastorello E, Tomelleri G, Vercelli L, Bruno C, Scapolan S, Siciliano G, Comacchio F (2008) Facioscapulohumeral muscular dystrophy: hearing loss and other atypical features of patients with large 4q35 deletions. Eur J Neurol 15:1353–1358CrossRefPubMed

42.

Tsuji M, Kinoshita M, Imai Y, Kawamoto M, Kohara N (2009) Facioscapulohumeral muscular dystrophy presenting with hypertrophic cardiomyopathy: a case study. Neuromuscul Disord 19:140–142CrossRefPubMed

43.

Uncini A, Galluzzi G, Di Muzio A, De Angelis MV, Ricci E, Scoppetta C, Servidei S (2002) Facioscapulohumeral muscular dystrophy presenting isolated monomelic lower limb atrophy. Report of two patients with and without 4q35 rearrangement. Neuromuscul Disord 12:874–877CrossRefPubMed

44.

van der Kooi AJ, Visser MC, Rosenberg N, van den Berg-Vos R, Wokke JH, Bakker E, de Visser M (2000) Extension of the clinical range of facioscapulohumeral dystrophy: report of six cases. J Neurol Neurosurg Psychiatry 69:114–116CrossRefPubMed

45.

Walter MC, Reilich P, Huebner A, Fischer D, Schroder R, Vorgerd M, Kress W, Born C, Schoser BG, Krause KH, Klutzny U, Bulst S, Frey JR, Lochmuller H (2007) Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P. Brain 130:1485–1496CrossRefPubMed

46.

Weis J, Kaussen M, Calvo S, Buonanno A (2000) Denervation induces a rapid nuclear accumulation of MRF4 in mature myofibers. Dev Dyn 218:438–451CrossRefPubMed

47.

Weis J, Schroder JM (1988) Adult polyglucosan body myopathy with subclinical peripheral neuropathy: case report and review of diseases associated with polyglucosan body accumulation. Clin Neuropathol 7:271–279PubMed

48.

Weis J, Schroder JM (1989) Differential effects of nerve, muscle, and fat tissue on regenerating nerve fibers in vivo. Muscle Nerve 12:723–734CrossRefPubMed

49.

Wood-Allum C, Brennan P, Hewitt M, Lowe J, Tyfield L, Wills A (2004) Clinical and histopathological heterogeneity in patients with 4q35 facioscapulohumeral muscular dystrophy (FSHD). Neuropathol Appl Neurobiol 30:188–191CrossRefPubMed

50.

Yamanaka G, Goto K, Matsumura T, Funakoshi M, Komori T, Hayashi YK, Arahata K (2001) Tongue atrophy in facioscapulohumeral muscular dystrophy. Neurology 57:733–735PubMed

Title: Facioscapulohumeral muscular dystrophy presenting with unusual phenotypes and atypical morphological features of vacuolar myopathy
Authors: Peter Reilich
Nicolai Schramm
Benedikt Schoser
Peter Schneiderat
Nicola Strigl-Pill
Josef Müller-Höcker
Wolfram Kress
Andreas Ferbert
Sabine Rudnik-Schöneborn
Johannes Noth
Hanns Lochmüller
Joachim Weis
Maggie C. Walter
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Journal of Neurology / Issue 7/2010
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-010-5471-1

At a glance: The STEP trials

Springer Medicine

Facioscapulohumeral muscular dystrophy presenting with unusual phenotypes and atypical morphological features of vacuolar myopathy

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 7/2010

Stroke: high rate of occult atrial fibrillation, effects of insulin on growth of infarction and stenting versus endarterectomy for treatment of carotid-artery stenosis

Identification of previously unreported mutations in CHRNA1, CHRNE and RAPSN genes in three unrelated Italian patients with congenital myasthenic syndromes

Central pontine and extrapontine myelinolysis: from epileptic and other manifestations to cognitive prognosis

Visual short-term memory binding in Alzheimer’s disease and depression

Communications of the European Neurological Society

Parkinson’s disease and 2009: recent advances