Dysphagia and esophageal dysfunction due to dystrophin deficient muscular dystrophy in a male Spanish water spaniel

McAtee, Brigitte B.; Heseltine, Johanna C.; Guo, Ling; Willard, Michael D.; Shelton, G. Diane

doi:10.1080/01652176.2018.1435939

Cited by 4 publications

(3 citation statements)

References 17 publications

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“… 15 Regrettably, in the present case, sections of the oesophagus and diaphragm were not collected at the post-mortem examination to determine whether the MD was associated with myofibre degeneration of the thoracic and abdominal oesophageal muscles or diaphragm, as noted in a Spanish Water Spaniel. 16 The use of clindamycin to treat the misdiagnosed Toxoplasma infection was considered as a possible cause of oesophageal injury; however, a classical stricture was not observed on swallow fluoroscopy and oesophagoscopy was declined.…”

Section: Discussionmentioning

confidence: 99%

Feline dystrophin-deficient muscular dystrophy misdiagnosed as Toxoplasma myositis

Reynolds,

Marks,

Guo

et al. 2024

Journal of Feline Medicine and Surgery Open Reports

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Case summary A 6-month-old male entire domestic shorthair cat presented for presumptive Toxoplasma myopathy that was non-responsive to antiprotozoal therapy. Clinical features included marked macroglossia, dysphagia, regurgitation, truncal muscle hypertrophy, pelvic limb gait abnormalities and megaoesophagus. Relevant diagnostics included serial creatine kinase activity, cardiac troponin I, fluoroscopic swallow study and routine muscle histopathology. Ultimately, post-mortem histopathology with immunostaining demonstrated markedly decreased or absent staining for the rod and carboxy terminus of dystrophin, confirming a dystrophin-deficient muscular dystrophy (MD). The misdiagnosis of toxoplasmosis was based on an increased IgG titre and muscle histopathology submitted to a local laboratory. Treatment for megaoesophagus included vertical feeding of wet food only, sildenafil and omeprazole. Dysphagia and regurgitation improved moderately. Presumptive hyperaesthesia and muscle pain were managed with anti-inflammatory doses of prednisolone. The patient was ultimately euthanased as a result of progressive MD signs and uraemia at 2 years of age. Relevance and novel information This case report highlights the collective clinical features of MD, as they could be considered pathognomonic for this rare condition and must be differentiated from other myopathies via specific immunostaining of muscle biopsies. This is crucial to obtain a correct and early diagnosis, allowing instigation of potentially valuable treatments. Megaoesophagus is an inconsistent feature in feline MD in addition to the more commonly observed oropharyngeal dysphagia. Management with a canned diet, sildenafil, omeprazole and upright feeding was beneficial with moderate improvement in the frequency of regurgitation. Prednisolone was thought to minimise the presumptive myalgia.

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Section: Discussionmentioning

confidence: 99%

Feline dystrophin-deficient muscular dystrophy misdiagnosed as Toxoplasma myositis

Reynolds,

Marks,

Guo

et al. 2024

Journal of Feline Medicine and Surgery Open Reports

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“…Dysphagia, muscle hypertrophy, and gait abnormalities are clinical signs that may be associated with diverse neuromuscular diseases, including but not limited to inflammatory myopathies [ 1 , 2 , 3 , 4 ], muscular dystrophies [ 5 , 6 , 7 ], non-dystrophic myotonias [ 8 , 9 , 10 , 11 , 12 ], and congenital myopathies associated with myostatin deficiency [ 13 , 14 ]. Specific variants have been identified in the dystrophin gene [ 15 ], sarcoglycan genes [ 15 , 16 ], the chloride channel gene [ 8 , 9 , 10 , 11 , 12 ], and the myostatin gene [ 13 , 14 ] that result in localized or generalized muscle hypertrophy with or without dysphagia.…”

Section: Introductionmentioning

confidence: 99%

Variants in CLCN1 and PDE4C Associated with Muscle Hypertrophy, Dysphagia, and Gait Abnormalities in Young French Bulldogs

Shelton,

Mickelson,

Friedenberg

et al. 2024

Animals

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(1) Background: Muscle hypertrophy, swallowing disorders, and gait abnormalities are clinical signs common to many muscle diseases, including muscular dystrophies, non-dystrophic myotonias, genetic myopathies associated with deficiency of myostatin, and acquired inflammatory myopathies. Here, we investigated underlying causes of this triad of clinical signs in four young French bulldogs via muscle histopathology coupled with whole genome and Sanger sequencing. (2) Methods: Dogs were evaluated by veterinary clinical internists and neurologists, and biopsies were obtained for histopathological diagnosis. DNA was submitted for whole genome sequencing, followed by bioinformatics evaluation and confirmation of variants via Sanger sequencing in two cases. (3) Results: Two novel variants were identified. The first, found in two related French bulldogs, was a homozygous variant in the chloride channel gene CLCN1 known to cause non-dystrophic congenital myotonia, and the second, found in an unrelated French bulldog, was a heterozygous variant in the cAMP phosphodiesterase gene PDE4C, which is the major phosphodiesterase expressed in skeletal muscle and may play a role in decreasing muscle atrophy. An underlying molecular basis in one other case has not yet been identified. (4) Conclusions: Here, we identified two novel variants, one in the CLCN1 and one in the PDE4C gene, associated with clinical signs of muscle hypertrophy, dysphagia, and gait abnormalities, and we suggested other bases of these phenotypes in French bulldogs that are yet to be discovered. Identification of genes and deleterious variants associated with these clinical signs may assist breeders in improving the overall health of this very popular breed and may lead to the identification of new therapies to reverse muscle atrophy in people and animals with neuromuscular diseases.

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“…In GRMD, a splice site mutation in intron 6 causes deletion (skipping) of exon 7 in the DMD transcript, with a resulting frameshift and premature stop codon in exon 8 [ 14 ]. Several additional DMD mutations, including variably sized deletions and insertions, have been characterized in other dogs [ 13 , 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

A novel canine model for Duchenne muscular dystrophy (DMD): single nucleotide deletion in DMD gene exon 20

López

Hammond²,

Rigsby

et al. 2018

Skeletal Muscle

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BackgroundBoys with Duchenne muscular dystrophy (DMD) have DMD gene mutations, with associated loss of the dystrophin protein and progressive muscle degeneration and weakness. Corticosteroids and palliative support are currently the best treatment options. The long-term benefits of recently approved compounds such as eteplirsen and ataluren remain to be seen. Dogs with naturally occurring dystrophinopathies show progressive disease akin to that of DMD. Accordingly, canine DMD models are useful for studies of pathogenesis and preclinical therapy development. A dystrophin-deficient, male border collie dog was evaluated at the age of 5 months for progressive muscle weakness and dysphagia.Case presentationDramatically increased serum creatine kinase levels (41,520 U/L; normal range 59–895 U/L) were seen on a biochemistry panel. Histopathologic changes characteristic of dystrophinopathy were seen. Dystrophin was absent in the skeletal muscle on immunofluorescence microscopy and western blot. Whole genome sequencing, polymerase chain reaction, and Sanger sequencing revealed a frameshift, single nucleotide deletion in canine DMD exon 20, position 27,626,466 (c.2841delT mRNA), resulting in a stop codon six nucleotides downstream. Semen was archived for future line perpetuation.ConclusionsThis spontaneous canine dystrophinopathy occurred due to a novel mutation in the minor DMD mutation hotspot (between exons 2 through 20). Perpetuating this line could allow for preclinical testing of genetic therapies targeted to this area of the DMD gene.Electronic supplementary materialThe online version of this article (10.1186/s13395-018-0162-1) contains supplementary material, which is available to authorized users.

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Dysphagia and esophageal dysfunction due to dystrophin deficient muscular dystrophy in a male Spanish water spaniel

Cited by 4 publications

References 17 publications

Feline dystrophin-deficient muscular dystrophy misdiagnosed as Toxoplasma myositis

Feline dystrophin-deficient muscular dystrophy misdiagnosed as Toxoplasma myositis

Variants in CLCN1 and PDE4C Associated with Muscle Hypertrophy, Dysphagia, and Gait Abnormalities in Young French Bulldogs

A novel canine model for Duchenne muscular dystrophy (DMD): single nucleotide deletion in DMD gene exon 20

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