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Mypopathy in Williams-Beuren syndrome

  • Neuropediatrics
  • Published:
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Abstract

Williams-Beuren syndrome (WBS) is a disorder of unknown aetiology. The classical features of the syndrome include a typical (‘elfin’) facies, mental retardation and heart defects. Myopathy has not so far been part of the spectrum of WBS. We studied six patients with WBS aged 3–25 years, five of whom showed clinical and morphological evidence of myopathy. The clinical manifestations of myopathy included hypotonia in infancy, walking delay, joint contractures, scoliosis, and increased exhaustion on exertion. These symptoms were present in variable expression but part of a typical postural pattern. Examination of muscle biopsies showed lipid storage in four patients and increased variability of fibre size in three. In one patient a muscle biopsy gave normal results. Biochemical investigation in four patients with morphological evidence of lipid storage in muscle revealed muscle carnitine deficiency in three. In addition, enzyme activities of fatty acid β-oxidation were low in one of two specimens tested. It is concluded that a clinically relevant myopathy is part of the multi-system manifestation of WBS and a clinical trial of carnitine supplementation is justified.

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Abbreviations

PPS:

peripheral pulmonary stenosis

SVAS:

supravalvular aortic stenosis

WBS:

Williams-Beuren syndrome

References

  1. Beuren AJ (1964b) Ein neues Syndrom: Supravalvuläre Aortenstenose, multiple periphere Pulmonalstenosen, geistige Retardierung, ähnliche Gesichtszüge und identische Zahnmißbildungen, Monatsschr Kinderheilkd 112: 218–221

    PubMed  Google Scholar 

  2. Beuren AJ (1972) Supravalvular aortic stenosis: a complex syndrome with and without mental retardation. Brith Defects 8: 45–55

    Google Scholar 

  3. Beuren AJ, Apitz J, Harmjanz D (1962) Supravalvular aortic stenosis in association with mental retardation and a certain facial appearance. Circulation 26: 1235–1240

    PubMed  Google Scholar 

  4. Beuren AJ, Schulze C, Eberle P, Harmjanz D, Apitz J (1964a) The syndrome of supravalvular aortic stenosis, peripheral pulmonary stenosis, mental retardation and similar facial appearance. Am J Cardiol 13: 471–483

    Article  PubMed  Google Scholar 

  5. Black IA, Bonham-Carter RE (1963) Association between aortic stenosis and facies of severe infantile hypercalcaemia. Lancet II: 745

    Article  Google Scholar 

  6. Burn J (1986) Williams syndrome. J Med Genet 23: 389–395

    PubMed  Google Scholar 

  7. Crisco JJ, Dobbs JM, Mulhern RK (1988) Cognitive processing of children with Williams syndrome. Dev Med Child Neurol 30: 650–656

    PubMed  Google Scholar 

  8. Culler FL, Jones KL, Deftos LJ (1985) Impaired calcitonin secretion in patients with Williams syndrome. J Pediatr 107: 720–723

    PubMed  Google Scholar 

  9. Dubowitz V (1985) Muscle biopsy. A practical approach, 2nd edn. Baillere Tindall, London

    Google Scholar 

  10. Engel AG (1986) Carnitine deficiency syndromes and lipid storage myopathies. In: Banker BQ, Engel AG (eds) Myology, McGraw Hill, New York, pp 1663–1696

    Google Scholar 

  11. Forbes GB, Bryson MF, Manning J, Amirhakimi GH, Reina JC (1972) Impaired calcium homeostasis in the infantile hypercalcemic syndrome. Acta Paediatr Scand 61: 305–309

    PubMed  Google Scholar 

  12. Friedmann WF, Roberts WC (1966) Vitamin D and the supravalvar aortic stenosis syndrome. The transplacental effects of vitamin D on the aorta of the rabbit. Circulation 34: 77–86

    PubMed  Google Scholar 

  13. Grimm T, Wesselhoeft W (1980) Zur Genetik des Williams-Beuren-Syndroms und der isolierten Form der supravalvulären Aortenstenose. Untersuchungen von 128 Familien. Z Kardiol 69: 168–172

    PubMed  Google Scholar 

  14. Hallidie-Smith KA, Karas S (1988) Cardiac anomalies in Williams-Beuren syndrome. Arch Dis Child 63: 809–813

    PubMed  Google Scholar 

  15. Hitman GA, Garde L, Daoud W, Snodgrass GJAI, Cohen RD (1989) The calcitonin-CGRP gene in the infantile hypercalcaemia/Williams-Beuren syndrome. J Med Genet 26: 609–613

    PubMed  Google Scholar 

  16. Hutchins GM, Mirvis SE, Mendelsohn G, Bulkley BH (1978) Supravalvular aortic stenosis with parafollicular cell (C-cell) hyperplasia. Am J Med 64: 967–973

    Article  PubMed  Google Scholar 

  17. Jones KL, Smith DW (1975) The Williams elfin facies syndrome. J Pediatr 86: 718–723

    PubMed  Google Scholar 

  18. Kaplan P, Kirschner M, Watters G, Costa MT (1989) Contractures in patients with Williams syndrome. Pediatrics 84: 895–899

    PubMed  Google Scholar 

  19. Maebashi M, Kawamura N, Sato M, Imamura A, Yoshinaga K, Suzuki M (1977a) Urinary excretion of carnitine in patients with hyperthyroidism and hypothyroidism: Augmentation by thyroid hormone. Metabolism 26: 351–356

    Article  PubMed  Google Scholar 

  20. Maebashi M, Kawamura N, Sato M, Imamura A, Yoshinaga K, Suzuki M (1977b) Urinary excretion of carnitine and serum concentration of carnitine and lipids in patients with hypofunctional endocrine diseases: involvement of adrenocorticoid and thyroid hormones in ACTH-induced augmentation of carnitine and lipid metabolism. Metabolism 26: 357–361

    Article  PubMed  Google Scholar 

  21. Martin NDT, Snodgrass GJAI, Cohen RD (1984) Idiopathic infantile hypercalcaemia — a continuing enigma. Arch Dis Child 59: 603–613

    PubMed  Google Scholar 

  22. McGarry JD, Foster DM (1976) An improved and simplified radioisotope assay for the determination of free and esterified carnitine. J Lipid Res 17: 277–281

    PubMed  Google Scholar 

  23. Morris CA, Demsey SA, Leonard CO, Dilts C, Blackburn BL (1988) Natural history of Williams syndrome: physical characteristics. J Pediatr 113: 318–326

    PubMed  Google Scholar 

  24. Preus M (1984) The Williams syndrome: objective definition and diagnosis. Med Genet 25: 422–428

    Google Scholar 

  25. Rebouche CJ, Engel AG (1983) Carnitine metabolism and deficiency syndromes. Mayo Clin Proc 58: 533–540

    PubMed  Google Scholar 

  26. Reichmann H, Rohkamm R, Zeviani M, Servidei S, Ricker K, DiMauro S (1986) Mitochondrial myopathy due to complex III deficiency with normal reducible cytochrome b concentration. Arch Neurol 43: 957–961

    PubMed  Google Scholar 

  27. Roe CR, Millington DS, Maltby DA, Bohan TP, Kahler SG, Chalmers RA (1985) Diagnostic and therapeutic implications of medium-chain acylcarnitines in the medium-chain acyl-CoA dehydrogenase deficiency. Pediatr Res 19: 459–466

    PubMed  Google Scholar 

  28. Trauner DA, Bellugi U, Chase C (1989) Neurologic features of Williams and Down syndromes. Pediatr Neurol 5: 166–168

    Article  PubMed  Google Scholar 

  29. Vernant P, Corone P, Rossignol AM, Bielman C (1980) Etude de 120 observations de syndrome de Williams et Beuren. Arch Mal Coeur 73: 661–666

    PubMed  Google Scholar 

  30. Wesselhoeft H, Salomon F, Grimm T (1980) Spektrum der supravalvulären Aortenstenose: Untersuchungsergebnisse bei 150 Patienten mit Williams-Beuren-Syndrom und der isolierten Form der supravalvulären Aortenstenose. Z Kardiol 69: 131–140

    PubMed  Google Scholar 

  31. Williams JCP, Barratt-Boyes BG, Lowe JB (1961) Supravalvular aortic stenosis. Circulation 24: 1311–1318

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Paediatrics, University of Düsseldorf, Moorenstrasse 5, W-4000, Düsseldorf, Germany

    T. Voit, H. Kramer & H. G. Lenard

  2. Department of Neuropathology, University of Düsseldorf, Moorenstrasse 5, W-4000, Düsseldorf, Germany

    C. Thomas & W. Wechsler

  3. Department of Neurology, University of Würzburg, Josef-Schneider-Strasse 11, W-8700, Würzburg, Germany

    H. Reichmann

Authors
  1. T. Voit
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  2. H. Kramer
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  3. C. Thomas
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  4. W. Wechsler
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  5. H. Reichmann
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  6. H. G. Lenard
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Additional information

The authors wish to dedicate this paper to the memory of Alois J. Beuren, MD, FACC

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Voit, T., Kramer, H., Thomas, C. et al. Mypopathy in Williams-Beuren syndrome. Eur J Pediatr 150, 521–526 (1991). https://doi.org/10.1007/BF01958438

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  • DOI: https://doi.org/10.1007/BF01958438

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