Clinical characteristics.

Dysferlinopathy includes a spectrum of muscle disease characterized by two major phenotypes: Miyoshi muscular dystrophy (MMD) and limb-girdle muscular dystrophy type 2B (LGMD2B); and two minor phenotypes: asymptomatic hyperCKemia and distal myopathy with anterior tibial onset (DMAT).

• MMD (median age of onset 19 years) is characterized by muscle weakness and atrophy, most marked in the distal parts of the legs, especially the gastrocnemius and soleus muscles. Over a period of years, the weakness and atrophy spread to the thighs and gluteal muscles. The forearms may become mildly atrophic with decrease in grip strength; the small muscles of the hands are spared.
• LGMD2B is characterized by early weakness and atrophy of the pelvic and shoulder girdle muscles in adolescence or young adulthood, with slow progression. Other phenotypes in this spectrum are scapuloperoneal syndrome and congenital muscular dystrophy.
• Asymptomatic hyperCKemia is characterized by marked elevation of serum CK concentration only.
• DMAT is characterized by early and predominant distal muscle weakness, particularly of the muscles of the anterior compartment of the legs.

Diagnosis/testing.

The diagnosis of dysferlinopathy is established in a proband with suggestive findings and biallelic pathogenic variants in DYSF identified by molecular genetic testing.

Management.

Treatment of manifestations: There is no approved therapy for dysferlinopathy. Treatment is symptomatic only. Management should be tailored to the individual and the specific subtype. Individualized management may include physical therapy, use of mechanical aids, surgical intervention for orthopedic complications, respiratory aids, and social and emotional support.

Surveillance: Annual monitoring of muscle strength, physical function, activities of daily living, joint range of motion, balance, and respiratory function, and for evidence of cardiomyopathy for individuals with cardiac involvement.

Agents/circumstances to avoid: Weight control to avoid obesity.

Genetic counseling.

Dysferlinopathy is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a DYSF pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the DYSF pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.

Suggestive Findings

Dysferlinopathy should be suspected in those with suggestive findings of major phenotypes and considered in those with suggestive findings of minor phenotypes. The diagnosis should be informed by family history.

Establishing the Diagnosis

The diagnosis of dysferlinopathy is established in a proband with Suggestive Findings and biallelic pathogenic variants in DYSF identified by molecular genetic testing (see Table 1).

Note: Identification of biallelic DYSF variants of uncertain significance (or identification of one known DYSF pathogenic variant and one DYSF variant of uncertain significance) does not establish or rule out a diagnosis of this disorder.

Molecular genetic testing approaches can include a combination of gene-targeted testing (single-gene testing or multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing) depending on the phenotype. Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not.

Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of a dysferlinopathy has not been considered are more likely to be diagnosed using genomic testing (see Option 2).

Clinical Description

Dysferlinopathy includes a spectrum of muscle disease characterized by two major phenotypes (Miyoshi muscular dystrophy [MMD] and limb-girdle muscular dystrophy type 2B [LGMD2B]) and two minor phenotypes (asymptomatic hyperCKemia and distal myopathy with anterior tibial onset [DMAT]) [Ueyama et al 2002]. The major and minor phenotypes can occur within families having the same pathogenic variants [Liu et al 1998, Weiler et al 1999, Illarioshkin et al 2000, Nakagawa et al 2001, Ueyama et al 2001].

The weakness and atrophy may be asymmetric with any of these presentations.

Miyoshi muscular dystrophy. Young adults have muscle weakness and atrophy most marked in the distal part of the legs, especially the gastrocnemius and soleus muscles. Early on, affected individuals are not able to stand on tiptoe, but retain the ability to stand on the heels. Over a period of years, the weakness and atrophy spread to the thighs and gluteal muscles, at which time climbing stairs, standing, and walking become difficult. The forearms may become mildly atrophic with decrease in grip strength; the small muscles of the hands are spared. The weakness may eventually include the shoulder girdle muscles [Mahjneh et al 2001].

Limb-girdle muscular dystrophy type 2B is characterized by early weakness and atrophy of the pelvic and shoulder girdle muscles that begins in adolescence or young adulthood, with slow progression. The spectrum of muscle involvement can also on occasion manifest as the scapuloperoneal syndrome with initial weakness of the shoulder girdle muscles combined with distal weakness of the legs or congenital muscular dystrophy with early onset – as observed, for example, in two sibs with hypotonia beginning between birth and age two months who had delayed motor development and serum CK concentrations that were normal or slightly elevated before age three years [Paradas et al 2009].

Asymptomatic hyperCKemia. Some individuals have only a marked elevation of serum CK concentration. This is usually considered a presymptomatic presentation of myopathy in an individual who eventually develops muscle weakness and atrophy. Sometimes the calf muscles are enlarged; this presentation may be confused with a dystrophinopathy (i.e., Duchenne or Becker muscular dystrophy).

Distal myopathy with anterior tibial onset is characterized by leg weakness that involves the muscles of the anterior compartment of the leg, causing foot drop [Illa et al 2001].

Histology. Muscle biopsy shows evidence of a dystrophy with random variation in fiber size and evidence of degeneration and regeneration. Type I fibers may predominate. There is often evidence of inflammation, sometimes leading to a misdiagnosis of polymyositis.

Genotype-Phenotype Correlations

Studies have reported genotype-phenotype correlates with the following two pathogenic variants [Takahashi et al 2003a, Takahashi et al 2013, Izumi et al 2020]:

• c.2997G>T was associated with a milder form of Miyoshi muscular dystrophy and LGMD2B
• c.3373delG was associated with Miyoshi muscular dystrophy.

Nomenclature

Dysferlinopathy was originally called LGMD2B because at the time that it was mapped to 2p13 it was the second form (2) of autosomal recessive (B) limb-girdle muscular dystrophy (LGMD) to be mapped. The gene for Miyoshi muscular dystrophy and the gene for LGMD2B were mapped to the same genetic interval at chromosome 2p13. Two groups independently identified a novel human skeletal muscle gene, DYSF, at this locus and documented that DYSF pathogenic variants cause both Miyoshi muscular dystrophy and LGMD2B.

Prevalence

The prevalence is not known. In the initial (1967) description of Miyoshi muscular dystrophy, four affected individuals in two families were from Japan.

Subsequently, Tagawa et al [2003] examined 107 unrelated Japanese individuals, including 53 with unclassified LGMD, 28 with Miyoshi muscular dystrophy, and 26 with other neuromuscular disorders. Using expression of dysferlin protein by immunohistochemistry (IHC) and mini-multiplex western blotting, they found deficiency of dysferlin protein by both methods in 19% of individuals with LGMD and 75% of individuals with Miyoshi muscular dystrophy.

In Libyan Jews, the prevalence of dysferlinopathy is at least 1:1,300, with a carrier rate of approximately 10% for the variant c.4872delG [Argov et al 2000].

A founder variant, c.2779delG, has been identified in Jews of the Caucasus [Leshinsky-Silver et al 2007].

A founder variant, c.5713C>T, has been identified in individuals from Spain [Vilchez et al 2005].

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with dysferlinopathy, the evaluations summarized in Table 4 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Treatment of Manifestations

There is no approved therapy for dysferlinopathy. Treatment is symptomatic only.

Management should be tailored to the individual and the specific subtype. A general approach to appropriate management can prolong survival and improve quality of life.

Surveillance

Routine follow up with the multidisciplinary team (annually or more frequently as determined by managing physician) is recommended. See Table 6.

Agents/Circumstances to Avoid

Control weight to avoid obesity; avoid use of steroids [Walter et al 2013].

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Comparison of the effect of prednisolone with vamorolone on dysferlin-deficient myofiber repair showed that vamorolone stabilized dysferlin-deficient muscle cell membrane and improved repair of dysferlin-deficient mouse myofibers [Sreetama et al 2018].

Exon skipping is a therapeutic approach that is feasible for various genetic disorders [Rodrigues & Yokota 2018]. Dominov et al [2019] designed antisense oligonucleotides (AONs) to bypass the effect of the affected individual’s pathogenic variant on RNA splicing. AON-mediated exon skipping corrected the aberrant pseudoexon splicing events in vitro, which increased normal mRNA production and significantly restored dysferlin protein expression [Dominov et al 2019].

Ono et al [2020] recently demonstrated that AMP-activated protein kinase (AMPK)γ1 was bound to a region of dysferlin, and AMPK complex was vital for the sarcolemmal damage repair of skeletal muscle fibers. Treatment with an AMPK activator rescued the membrane-repair impairment observed in immortalized human myotubes with reduced expression of dysferlin and dysferlin-null mouse fibers [Ono et al 2020].

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Mode of Inheritance

Dysferlinopathy is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

• The parents of an affected individual are obligate heterozygotes (i.e., presumed to be carriers of one DYSF pathogenic variant based on family history).
• Molecular genetic testing is recommended for the parents of a proband to confirm that both parents are heterozygous for a DYSF pathogenic variant and to allow reliable recurrence risk assessment. If a pathogenic variant is detected in only one parent, the following possibilities should be considered:
  • One of the pathogenic variants identified in the proband occurred as a de novo event in the proband or as a postzygotic de novo event in a mosaic parent [Jónsson et al 2017].
  • Uniparental isodisomy for the parental chromosome with the pathogenic variant resulted in homozygosity for the pathogenic variant in the proband.
• Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Sibs of a proband

• If both parents are known to be heterozygous for a DYSF pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
• Intrafamilial clinical variability may be observed between sibs who inherit biallelic DYSF pathogenic variants; for example, Miyoshi muscular dystrophy, limb-girdle muscular dystrophy type 2B, and distal myopathy with anterior tibial onset have been reported in the same family [Saito et al 2007].
• Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Offspring of a proband. The offspring of an individual with dysferlinopathy are obligate heterozygotes (carriers) for a pathogenic variant in DYSF.

Other family members. Each sib of the proband's parents is at a 50% risk of being a carrier of a DYSF pathogenic variant.

Carrier Detection

Carrier testing for at-risk relatives requires prior identification of the DYSF pathogenic variants in the family.

Related Genetic Counseling Issues

Family planning

• The optimal time for determination of genetic risk and discussion of the availability of prenatal and preimplantation genetic testing is before pregnancy.
• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

Prenatal Testing and Preimplantation Genetic Testing

Once the DYSF pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.

Molecular Pathogenesis

Dysferlin is expressed in the plasma membrane of skeletal muscles and is involved in calcium-mediated membrane fusion events and plasma membrane repair [Bansal et al 2003, Lennon et al 2003].

Mechanism of disease causation. Loss-of-function variants result in very low levels of dysferlin expression in skeletal muscle membranes.

DYSF-specific laboratory technical considerations

• DYSF RNA analysis from muscle cells or myogenic cells transduced from skin fibroblasts can be useful in identifying variants affecting splicing [Dominov et al 2019].
• Dysferlin immunohistochemical and immunoblot analyses on muscle tissue that identify dysferlin protein deficiency can assist in interpretation of variants of uncertain significance. However, dysferlin expression can also be reduced in other muscular dystrophies: dystrophinopathy [Piccolo et al 2000], sarcoglycanopathy [Piccolo et al 2000], caveolinopathy [Matsuda et al 2001], and calpainopathy [Tagawa et al 2003].

Revision History

• 27 May 2021 (bp) Comprehensive update posted live
• 5 March 2015 (me) Comprehensive update posted live
• 22 April 2010 (me) Comprehensive update posted live
• 19 April 2006 (me) Comprehensive update posted live
• 5 February 2004 (me) Review posted live
• 24 September 2003 (ma) Original submission

Literature Cited

• Argov Z, Sadeh M, Mazor K, Soffer D, Kahana E, Eisenberg I, Mitrani-Rosenbaum S, Richard I, Beckmann J, Keers S, Bashir R, Bushby K, Rosenmann H. Muscular dystrophy due to dysferlin deficiency in Libyan Jews. Clinical and genetic features. Brain. 2000;123:1229–37. [PubMed: 10825360]
• Bansal D, Miyake K, Vogel SS, Groh S, Chen CC, Williamson R, McNeil PL, Campbell KP. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature. 2003;423:168–72. [PubMed: 12736685]
• Dominov JA, Uyan Ö, McKenna-Yasek D, Nallamilli BRR, Kergourlay V, Bartoli M, Levy N, Hudson J, Evangelista T, Lochmuller H, Krahn M, Rufibach L, Hegde M, Brown RH Jr. Correction of pseudoexon splicing caused by a novel intronic dysferlin mutation. Ann Clin Transl Neurol. 2019;6:642–54. [PMC free article: PMC6469257] [PubMed: 31019989]
• Harris E, Bladen CL, Mayhew A, James M, Bettinson K, Moore U, Smith FE, Rufibach L, Cnaan A, Bharucha-Goebel DX, Blamire AM, Bravver E, Carlier PG, Day JW, Díaz-Manera J, Eagle M, Grieben U, Harms M, Jones KJ, Lochmüller H, Mendell JR, Mori-Yoshimura M, Paradas C, Pegoraro E, Pestronk A, Salort-Campana E, Schreiber-Katz O, Semplicini C, Spuler S, Stojkovic T, Straub V, Takeda S, Tesi Rocha C, Walter MC, Bushby K, et al. The clinical outcome study for dysferlinopathy: an international multicenter study. Neurol Genet. 2016;2:e89. [PMC free article: PMC4994875] [PubMed: 27602406]
• Harris-Love MO, Joe G, Davenport TE, Koziol D, Abbett Rose K, Shrader JA, Vasconcelos OM, McElroy B, Dalakas MC. Reliability of the Adult Myopathy Assessment Tool in individuals with myositis. Arthritis Care Res (Hoboken). 2015;67:563–70. [PMC free article: PMC4450351] [PubMed: 25201624]
• Illa I, Serrano-Munuera C, Gallardo E, Lasa A, Rojas-Garcia R, Palmer J, Gallano P, Baiget M, Matsuda C, Brown RH. Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype. Ann Neurol. 2001;49:130–4. [PubMed: 11198284]
• Illarioshkin SN, Ivanova-Smolenskaya IA, Greenberg CR, Nylen E, Sukhorukov VS, Poleshchuk VV, Markova ED, Wrogemann K. Identical dysferlin mutation in limb-girdle muscular dystrophy type 2B and distal myopathy. Neurology. 2000;55:1931–3. [PubMed: 11134403]
• Izumi R, Takahashi T, Suzuki N, Niihori T, Ono H, Nakamura N, Katada S, Kato M, Warita H, Tateyama M, Aoki M. The genetic profile of dysferlinopathy in a cohort of 209 cases: Genotype–phenotype relationship and a hotspot on the inner DysF domain. Hum Mutat. 2020;41:1540–54. [PubMed: 32400077]
• Jebsen RH, Taylor N, Trieschmann RB, Trotter MJ, Howard LA. An objective and standardized test of hand function. Arch Phys Med Rehabil. 1969;50:311–9. [PubMed: 5788487]
• Jónsson H, Sulem P, Kehr B, Kristmundsdottir S, Zink F, Hjartarson E, Hardarson MT, Hjorleifsson KE, Eggertsson HP, Gudjonsson SA, Ward LD, Arnadottir GA, Helgason EA, Helgason H, Gylfason A, Jonasdottir A, Jonasdottir A, Rafnar T, Frigge M, Stacey SN, Th Magnusson O, Thorsteinsdottir U, Masson G, Kong A, Halldorsson BV, Helgason A, Gudbjartsson DF, Stefansson K. Parental influence on human germline de novo mutations in 1,548 trios from Iceland. Nature. 2017;549:519–22. [PubMed: 28959963]
• Lennon NJ, Kho A, Bacskai BJ, Perlmutter SL, Hyman BT, Brown RH Jr. Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing. J Biol Chem. 2003;278:50466–73. [PubMed: 14506282]
• Leshinsky-Silver E, Argov Z, Rozenboim L, Cohen S, Tzofi Z, Cohen Y, Wirguin Y, Dabby R, Lev D, Sadeh M. Dysferlinopathy in the Jews of the Caucasus: a frequent mutation in the dysferlin gene. Neuromuscul Disord. 2007;17:950–4. [PubMed: 17825554]
• Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, Serrano C, Urtizberea JA, Hentati F, Hamida MB, Bohlega S, Culper EJ, Amato AA, Bossie K, Oeltjen J, Bejaoui K, McKenna-Yasek D, Hosler BA, Schurr E, Arahata K, de Jong PJ, Brown RH Jr. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet. 1998;20:31–6. [PubMed: 9731526]
• Mahjneh I, Marconi G, Bushby K, Anderson LV, Tolvanen-Mahjneh H, Somer H. Dysferlinopathy (LGMD2B): a 23-year follow-up study of 10 patients homozygous for the same frameshifting dysferlin mutations. Neuromuscul Disord. 2001;11:20–6. [PubMed: 11166162]
• Matsuda C, Hayashi YK, Ogawa M, Aoki M, Murayama K, Nishino I, Nonaka I, Arahata K, Brown RH Jr. The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. Hum Mol Genet. 2001;10:1761–6. [PubMed: 11532985]
• Nakagawa M, Matsuzaki T, Suehara M, Kanzato N, Takashima H, Higuchi I, Matsumura T, Goto K, Arahata K, Osame M. Phenotypic variation in a large Japanese family with Miyoshi myopathy with nonsense mutation in exon 19 of dysferlin gene. J Neurol Sci. 2001;184:15–9. [PubMed: 11231027]
• Ono H, Suzuki N, Kanno S, Kawahara G, Izumi R, Takahansi T, Kitajima Y, Osana S, Nakamura N, Akiyama T, Ikeda K, Shijo T, Mitsuzawa S, Nagatomi R, Araki N, Yasui A, Warita H, Hayashi YK, Miyake K, Aoki M. AMPK complex activation promotes sarcolemmal repair in dysferlinopathy. Mol Ther. 2020;28:1133–53. [PMC free article: PMC7132631] [PubMed: 32087766]
• Paradas C, González-Quereda L, De Luna N, Gallardo E, García-Consuegra I, Gómez H, Cabello A, Illa I, Gallano P. A new phenotype of dysferlinopathy with congenital onset. Neuromuscul Disord. 2009;19:21–5. [PubMed: 19084402]
• Piccolo F, Moore SA, Ford GC, Campbell KP. Intracellular accumulation and reduced sarcolemmal expression of dysferlin in limb-girdle muscular dystrophies. Ann Neurol. 2000;48:902–12. [PubMed: 11117547]
• Rodrigues M, Yokota T. An overview of recent advances and clinical applications of exon skipping and splice modulation for muscular dystrophy and various genetic diseases. Methods Mol Biol. 2018;1828:31–55. [PubMed: 30171533]
• Saito H, Suzuki N, Ishiguro H, Hirota K, Itoyama Y, Takahashi T, Aoki M. Distal anterior compartment myopathy with early ankle contractures. Muscle Nerve. 2007;36:525–7. [PubMed: 17614318]
• Sreetama SC, Chandra G, Van der Meulen JH, Ahmad MM, Suzuki P, Bhuvanendran S, Nagaraju K, Hoffman EP, Jaiswal JK. Membrane stabilization by modified steroid offers a potential therapy for muscular dystrophy due to dysferlin deficit. Mol Ther. 2018;26:2231–42. [PMC free article: PMC6127637] [PubMed: 30166241]
• Tagawa K, Ogawa M, Kawabe K, Yamanaka G, Matsumura T, Goto K, Nonaka I, Nishino I, Hayashi YK. Protein and gene analyses of dysferlinopathy in a large group of Japanese muscular dystrophy patients. J Neurol Sci. 2003;211:23–8. [PubMed: 12767493]
• Takahashi T, Aoki M, Suzuki N, Tateyama M, Yaginuma C, Sato H, Hayasaka M, Sugawara H, Ito M, Abe-Kondo E, Shimakura N, Ibi T, Kuru S, Wakayama T, Sobue G, Fujii N, Saito T, Matsumura T, Funakawa I, Mukai E, Kawanami T, Morita M, Yamazaki M, Hasegawa T, Shimizu J, Tsuji S, Kuzuhara S, Tanaka H, Yoshioka M, Konno H, Onodera H, Itoyama Y. Clinical features and a mutation with late onset of limb girdle muscular dystrophy 2B. J Neurol Neurosurg Psychiatry. 2013;84:433–40. [PMC free article: PMC3595148] [PubMed: 23243261]
• Takahashi T, Aoki M, Tateyama M, Kondo E, Mizuno T, Onodera Y, Takano R, Kawai H, Kamakura K, Mochizuki H, Shizuka-Ikeda M, Nakagawa M, Yoshida Y, Akanuma J, Hoshino K, Saito H, Nishizawa M, Kato S, Saito K, Miyachi T, Yamashita H, Kawai M, Matsumura T, Kuzuhara S, Ibi T, Sahashi K, Nakai H, Kohnosu T, Nonaka I, Arahata K, Brown RH Jr, Saito H, Itoyama Y. Dysferlin mutations in Japanese Miyoshi myopathy: Relationship to phenotype. Neurology. 2003a;60:1799–804. [PubMed: 12796534]
• Takahashi T, Aoki M, Tateyama M, Onodera Y, Kondo E, Sato H, Ito M, Yoshioka M, Konno K, Brown RH Jr, Saito H, Itoyama Y (2003b) Mutational and clinical features of Japanese patients with dysferlinopathy. Neurology 60 Suppl A:233.
• Ueyama H, Kumamoto T, Horinouchi H, Fujimoto S, Aono H, Tsuda T. Clinical heterogeneity in dysferlinopathy. Intern Med. 2002;41:532–6. [PubMed: 12132520]
• Ueyama H, Kumamoto T, Nagao S, Masuda T, Horinouchi H, Fujimoto S, Tsuda T. A new dysferlin gene mutation in two Japanese families with limb-girdle muscular dystrophy 2B and Miyoshi myopathy. Neuromuscul Disord. 2001;11:139–45. [PubMed: 11257469]
• Vilchez JJ, Gallano P, Gallardo E, Lasa A, Rojas-Garcia R, Freixas A, De Luna N, Calafell F, Sevilla T, Mayordomo F, Baiget M, Illa I. Identification of a novel founder mutation in the DYSF gene causing clinical variability in the Spanish population. Arch Neurol. 2005;62:1256–9. [PubMed: 16087766]
• Visser J, Mans E, de Visser M, van den Berg-Vos RM, Franssen H, de Jong JM, van den Berg LH, Wokke JH, de Haan RJ. Comparison of maximal voluntary isometric contraction and hand-held dynamometry in measuring muscle strength of patients with progressive lower motor neuron syndrome. Neuromuscul Disord. 2003;13:744–50. [PubMed: 14561498]
• Walter MC, Reilich P, Thiele S, Schessl J, Schreiber H, Reiners K, Kress W, Müller-Reible C, Vorgerd M, Urban P, Schrank B, Deschauer M, Schlotter-Weigel B, Kohnen R, Lochmüller H. Treatment of dysferlinpathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis. 2013;8:26. [PMC free article: PMC3617000] [PubMed: 23406536]
• Weiler T, Bashir R, Anderson LV, Davison K, Moss JA, Britton S, Nylen E, Keers S, Vafiadaki E, Greenberg CR, Bushby CR, Wrogemann K. Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s). Hum Mol Genet. 1999;8:871–7. [PubMed: 10196377]