Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2016

Open Access 01-12-2016 | Research

MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients

Authors: C. Fiorillo, G. Astrea, M. Savarese, D. Cassandrini, G. Brisca, F. Trucco, M. Pedemonte, R. Trovato, L. Ruggiero, L. Vercelli, A. D’Amico, G. Tasca, M. Pane, M. Fanin, L. Bello, P. Broda, O. Musumeci, C. Rodolico, S. Messina, G. L. Vita, M. Sframeli, S. Gibertini, L. Morandi, M. Mora, L. Maggi, A. Petrucci, R. Massa, M. Grandis, A. Toscano, E. Pegoraro, E. Mercuri, E. Bertini, T. Mongini, L. Santoro, V. Nigro, C. Minetti, F. M. Santorelli, C. Bruno, on behalf of the Italian Network on Congenital Myopathies

Published in: Orphanet Journal of Rare Diseases | Issue 1/2016

Login to get access

Abstract

Background

Myosin heavy chain 7 (MYH7)-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions.

Results

As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7. Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps.

Conclusion

This work adds to the genotype-phenotype correlation of MYH7-relatedmyopathies confirming the complexity of the disorder.
Appendix
Available only for authorised users
Literature
1.
Tajsharghi H, Thornell LE, Lindberg C, Lindvall B, Henriksson KG, Oldfors A. Myosin storage myopathy associated with a heterozygous missense mutation in MYH7. Ann Neurol. 2003;54(4):494–500.CrossRefPubMed
2.
Walsh R, Rutland C, Thomas R, Loughna S. Cardiomyopathy: a systematic review of disease-causing mutations in myosin heavy chain 7 and their phenotypic manifestations. Cardiology. 2010;115(1):49–60.CrossRefPubMed
3.
Pegoraro E, Gavassini BF, Borsato C, Melacini P, Vianello A, et al. MYH7 gene mutation in myosin storage myopathy and scapulo-peroneal myopathy. Neuromuscul Disord. 2007;17(4):321–9.CrossRefPubMed
4.
Cullup T, Lamont PJ, Cirak S, Damian MS, Wallefeld W, et al. Mutations in MYH7 cause Multi-minicore Disease (MmD) with variable cardiac involvement. Neuromuscul Disord. 2012;22(12):1096–104.CrossRefPubMed
5.
Clarke NF, Amburgey K, Teener J, Camelo-Piragua S, Kesari A, et al. A novel mutation expands the genetic and clinical spectrum of MYH7-related myopathies. Neuromuscul Disord. 2013;23(5):432–6.CrossRefPubMedPubMedCentral
6.
Ortolano S, Tarrío R, Blanco-Arias P, Teijeira S, Rodríguez-Trelles F, et al. A novel MYH7 mutation links congenital fiber type disproportion and myosin storage myopathy. Neuromuscul Disord. 2011;21(4):254–62.CrossRefPubMed
7.
Ruggiero L, Fiorillo C, Gibertini S, De Stefano F, Manganelli F, et al. A rare mutation in MYH7 gene occurs with overlapping phenotype. Biochem Biophys Res Commun. 2015;457(3):262–6.CrossRefPubMed
8.
Tajsharghi H, Oldfors A, Macleod DP, Swash M. Homozygous mutation in MYH7 in myosin storage myopathy and cardiomyopathy. Neurology. 2007;68(12):962.CrossRefPubMed
9.
Yüceyar N, Ayhan Ö, Karasoy H, Tolun A. Homozygous MYH7 R1820W mutation results in recessive myosin storage myopathy: scapuloperoneal and respiratory weakness with dilated cardiomyopathy. Neuromuscul Disord. 2015;25(4):340–4.CrossRefPubMed
10.
Rayment I, Holden HM, Sellers JR, Fananapazir L, Epstein ND. Structural interpretation of the mutations in the beta-cardiac myosin that have been implicated in familial hypertrophic cardiomyopathy. Proc Natl Acad Sci U S A. 1995;92(9):3864–8.CrossRefPubMedPubMedCentral
11.
Udd B. 165th ENMC International Workshop: distal myopathies 6-8th February 2009 Naarden, The Netherlands. Neuromuscul Disord. 2009;19(6):429–38.CrossRefPubMed
12.
Savarese M, Di Fruscio G, Mutarelli M, Torella A, Magri F, Santorelli FM, Comi GP, Bruno C, Nigro V. MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples. Acta Neuropathol Commun. 2014;2:100.CrossRefPubMedPubMedCentral
13.
Mutarelli M, Marwah V, Rispoli R, Carrella D, Dharmalingam G, Oliva G, di Bernardo D. A community-based resource for automatic exome variant-calling and annotation in Mendelian disorders. BMC Genomics. 2014;15 Suppl 3:S5.CrossRefPubMedPubMedCentral
14.
Lupas A, Van Dyke M, Stock J. Predicting coiled coils from protein sequences. Science. 1991;252(5009):1162–4.CrossRefPubMed
15.
Rampersaud E, Siegfried JD, Norton N, Li D, Martin E, Hershberger RE. Rare variant mutations identified in pediatric patients with dilated cardiomyopathy. Prog Pediatr Cardiol. 2011;31(1):39–47.CrossRefPubMedPubMedCentral
16.
Park JM, Kim YJ, Yoo JH, Hong YB, Park JH, et al. A novel MYH7 mutation with prominent paraspinal and proximal muscle involvement. Neuromuscul Disord. 2013;23(7):580–6.CrossRefPubMed
17.
Roncarati R, Latronico MV, Musumeci B, Aurino S, Torella A, Bang ML, Jotti GS, Puca AA, Volpe M, Nigro V, Autore C, Condorelli G. Unexpectedly low mutation rates in beta-myosin heavy chain and cardiac myosin binding protein genes in Italian patients with hypertrophic cardiomyopathy. J Cell Physiol. 2011;226(11):2894–900.CrossRefPubMedPubMedCentral
18.
Darin N, Tajsharghi H, Ostman-Smith I, Gilljam T, Oldfors A. New skeletal myopathy and cardiomyopathy associated with a missense mutation in MYH7. Neurology. 2007;68(23):2041–2.CrossRefPubMed
19.
Fokstuen S, Munoz A, Melacini P, Iliceto S, Perrot A, et al. Rapid detection of genetic variants in hypertrophic cardiomyopathy by custom DNA resequencing array in clinical practice. J Med Genet. 2011;48(8):572–6.CrossRefPubMed
20.
Girolami F, Olivotto I, Passerini I, Zachara E, Nistri S, Re F, Fantini S, Baldini K, Torricelli F, Cecchi F. A molecular screening strategy based on beta-myosin heavy chain, cardiac myosin binding protein C and troponin T genes in Italian patients with hypertrophic cardiomyopathy. J Cardiovasc Med (Hagerstown). 2006;7(8):601–7.CrossRef
21.
Pajusalu S, Talvik I, Noormets K, Talvik T, Põder H, et al. De novo exonic mutation in MYH7 gene leading to exon skipping in a patient with early onset muscular weakness and fiber-type disproportion. Neuromuscul Disord. 2016;26(3):236-9.
22.
Lamont PJ, Wallefeld W, Hilton-Jones D, Udd B, Argov Z, et al. Novel mutations widen the phenotypic spectrum of slow skeletal/β-cardiac myosin (MYH7) distal myopathy. Hum Mutat. 2014;35(7):868–79.CrossRefPubMedPubMedCentral
23.
Tajsharghi H, Oldfors A. Myosinopathies: pathology and mechanisms. Acta Neuropathol. 2013;125(1):3–18.CrossRefPubMed
24.
Homayoun H, Khavandgar S, Hoover JM, Mohsen AW, Vockley J, et al. Novel mutation in MYH7 gene associated with distal myopathy and cardiomyopathy. Neuromuscul Disord. 2011;21(3):219–22.CrossRefPubMed
25.
Uro-Coste E, Arné-Bes MC, Pellissier JF, Richard P, Levade T, Heitz F, Figarella-Branger D, Delisle MB. Striking phenotypic variability in two familial cases of myosin storage myopathy with a MYH7 Leu1793pro mutation. Neuromuscul Disord. 2009;19(2):163–6.CrossRefPubMed
26.
Muelas N, Hackman P, Luque H, Garcés-Sánchez M, Azorín I, Suominen T, Sevilla T, Mayordomo F, Gómez L, Martí P, María Millán J, Udd B, Vílchez JJ. MYH7 gene tail mutation causing myopathic profiles beyond Laing distal myopathy. Neurology. 2010;75(8):732–41.CrossRefPubMed
27.
Finsterer J, Brandau O, Stöllberger C, Wallefeld W, Laing NG, Laccone F. Distal myosin heavy chain-7 myopathy due to the novel transition c.5566G > A (p.E1856K) with high interfamilial cardiac variability and putative anticipation. Neuromuscul Disord. 2014;24(8):721–5.CrossRefPubMed
28.
Sewry CA, Müller C, Davis M, Dwyer JS, Dove J, et al. The spectrum of pathology in central core disease. Neuromuscul Disord. 2002;12(10):930–8.CrossRefPubMed
29.
Bohlega S, Abu-Amero SN, Wakil SM, Carroll P, Al-Amr R, Lach B, Al-Sayed Y, Cupler EJ, Meyer BF. Mutation of the slow myosin heavy chain rod domain underlies hyaline body myopathy. Neurology. 2004;62(9):1518–21.CrossRefPubMed
30.
Shingde MV, Spring PJ, Maxwell A, Wills EJ, Harper CG, Dye DE, Laing NG, North KN. Myosin storage (hyaline body) myopathy: a case report. Neuromuscul Disord. 2006;16(12):882–6.CrossRefPubMed
31.
Laing NG, Laing BA, Meredith C, Wilton SD, Robbins P, et al. Autosomal dominant distal myopathy: linkage to chromosome 14. Am J Hum Genet. 1995;56(2):422–7.PubMedPubMedCentral
32.
Muelas N, Hackman P, Luque H, Suominen T, Espinós C, et al. Spanish MYH7 founder mutation of Italian ancestry causing a large cluster of Laing myopathy patients. Clin Genet. 2012;81(5):491–4.CrossRefPubMed
33.
Tasca G, Ricci E, Penttilä S, Monforte M, Giglio V, Ottaviani P, Camastra G, Silvestri G, Udd B. New phenotype and pathology features in MYH7-related distal myopathy. Neuromuscul Disord. 2012;22(7):640–7.CrossRefPubMed
34.
Quijano-Roy S, Carlier RY, Fischer D. Muscle imaging in congenital myopathies. Semin Pediatr Neurol. 2011;18(4):221–9. Review.CrossRefPubMed
35.
Astrea G, Brisca G, Fiorillo C, Valle M, Tosetti M, et al. Muscle MRI in TRPV4-related congenital distal SMA. Neurology. 2012;78(5):364–5.CrossRefPubMed
36.
Meredith C, Herrmann R, Parry C, Liyanage K, Dye DE, et al. Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause Laing early-onset distal myopathy (MPD1). Am J Hum Genet. 2004;75(4):703–8.CrossRefPubMedPubMedCentral
37.
Hershberger RE, Parks SB, Kushner JD, Li D, Ludwigsen S, et al. Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy. Clin Transl Sci. 2008;1(1):21–6.CrossRefPubMedPubMedCentral
Metadata
Title
MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients
Authors
C. Fiorillo
G. Astrea
M. Savarese
D. Cassandrini
G. Brisca
F. Trucco
M. Pedemonte
R. Trovato
L. Ruggiero
L. Vercelli
A. D’Amico
G. Tasca
M. Pane
M. Fanin
L. Bello
P. Broda
O. Musumeci
C. Rodolico
S. Messina
G. L. Vita
M. Sframeli
S. Gibertini
L. Morandi
M. Mora
L. Maggi
A. Petrucci
R. Massa
M. Grandis
A. Toscano
E. Pegoraro
E. Mercuri
E. Bertini
T. Mongini
L. Santoro
V. Nigro
C. Minetti
F. M. Santorelli
C. Bruno
on behalf of the Italian Network on Congenital Myopathies
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2016
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-016-0476-1

Other articles of this Issue 1/2016

Orphanet Journal of Rare Diseases 1/2016 Go to the issue

Review

The P42 peptide and Peptide-based therapies for Huntington’s disease

Letter to the Editor

The medical experience of a patient with a rare disease and her family

Research

A homozygous splicing mutation in ELAC2 suggests phenotypic variability including intellectual disability with minimal cardiac involvement

Research

Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study

Research

Establishment of reference values of α-tocopherol in plasma, red blood cells and adipose tissue in healthy children to improve the management of chylomicron retention disease, a rare genetic hypocholesterolemia

Research

Quality of life, fatigue and mental health in patients with the m.3243A > G mutation and its correlates with genetic characteristics and disease manifestation