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Brody myopathy(BROD)

MedGen UID:: 371441
•Concept ID:: C1832918
•: Disease or Syndrome

Synonym:	BRODY DISEASE
SNOMED CT:	Brody myopathy (703530005); Brody disease (703530005)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal recessive inheritance (Orphanet) Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	ATP2A1 (16p11.2)

Monarch Initiative:	MONDO:0010977
OMIM®:	601003
Orphanet:	ORPHA53347

Definition

Brody disease (BROD) is an autosomal recessive skeletal muscle disorder characterized by exercise-induced muscle stiffness and cramps primarily affecting the arms, legs, and eyelids, although more generalized muscle involvement may also occur. Symptom onset is most often in the first decade, but many patients present and are diagnosed later in life. Skeletal muscle biopsy typically shows variation in fiber size, increased internal nuclei, and atrophy of type II muscle fibers. Rare patients have been reported to develop malignant hyperthermia after administration of anesthesia, suggesting that patients with the disorder should be tested. The disorder results from defective relaxation of fast-twitch (type II) skeletal muscle fibers due to defects in calcium homeostasis and reuptake in the muscle fiber (summary by Odermatt et al., 2000 and Molenaar et al., 2020). [from OMIM]

Additional description

From MedlinePlus Genetics
Brody myopathy is a condition that affects the skeletal muscles, which are the muscles used for movement. Affected individuals experience muscle cramping and stiffening after exercise or other strenuous activity, especially in cold temperatures. These symptoms typically begin in childhood. They are usually painless, but in some cases can cause mild discomfort. The muscles usually relax after a few minutes of rest. Most commonly affected are the muscles of the arms, legs, and face (particularly the eyelids).

In some people with Brody myopathy, exercise leads to the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. https://medlineplus.gov/genetics/condition/brody-myopathy

Clinical features

From HPO

Myalgia

MedGen UID:: 68541
•Concept ID:: C0231528
•: Sign or Symptom

Pain in muscle.

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Fasciculations

MedGen UID:: 5124
•Concept ID:: C0015644
•: Sign or Symptom

Fasciculations are observed as small, local, involuntary muscle contractions (twitching) visible under the skin. Fasciculations result from increased irritability of an axon (which in turn is often a manifestation of disease of a motor neuron). This leads to sporadic discharges of all the muscle fibers controlled by the axon in isolation from other motor units.

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Abnormal reflex

MedGen UID:: 19707
•Concept ID:: C0034933
•: Finding

Any anomaly of a reflex, i.e., of an automatic response mediated by the nervous system (a reflex does not need the intervention of conscious thought to occur).

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Myokymia

MedGen UID:: 146882
•Concept ID:: C0684219
•: Sign or Symptom

Myokymia consists of involuntary, fine, continuous, undulating contractions that spread across the affected striated muscle.

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Motor delay

MedGen UID:: 381392
•Concept ID:: C1854301
•: Finding

A type of Developmental delay characterized by a delay in acquiring motor skills.

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Somatic sensory dysfunction

MedGen UID:: 1790456
•Concept ID:: C5551413
•: Finding

An abnormality of the primary sensation that is mediated by peripheral nerves (pain, temperature, touch, vibration, joint position). The word hypoesthesia (or hypesthesia) refers to a reduction in cutaneous sensation to a specific type of testing.

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Muscle weakness

MedGen UID:: 57735
•Concept ID:: C0151786
•: Finding

Reduced strength of muscles.

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Flexion contracture

MedGen UID:: 83069
•Concept ID:: C0333068
•: Anatomical Abnormality

A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.

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Difficulty running

MedGen UID:: 108251
•Concept ID:: C0560346
•: Finding

Reduced ability to run.

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Myotonia

MedGen UID:: 675119
•Concept ID:: C0700153
•: Finding

An involuntary and painless delay in the relaxation of skeletal muscle following contraction or electrical stimulation.

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Percussion myotonia

MedGen UID:: 148293
•Concept ID:: C0751359
•: Finding

A localized myotonic contraction in a muscle in reaction to percussion (tapping with the examiner's finger, a rubber percussion hammer, or a similar object).

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Exercise-induced muscle cramps

MedGen UID:: 383715
•Concept ID:: C1855578
•: Finding

Sudden and involuntary contractions of one or more muscles brought on by physical exertion.

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Exercise-induced muscle stiffness

MedGen UID:: 343388
•Concept ID:: C1855579
•: Finding

A type of muscle stiffness that occurs following physical exertion.

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Skeletal muscle hypertrophy

MedGen UID:: 853739
•Concept ID:: C2265792
•: Finding

Abnormal increase in muscle size and mass not due to training.

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EMG: myotonic discharges

MedGen UID:: 867779
•Concept ID:: C4022169
•: Finding

High frequency discharges in electromyography (EMG) that vary in amplitude and frequency, waxing and waning continuously with firing frequencies ranging from 150/second down to 20/second and producing a sound that has been referred to as a dive bomber sound.

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Malignant hyperthermia

MedGen UID:: 1830388
•Concept ID:: C5779784
•: Pathologic Function

Malignant hyperthermia is characterized by a rapid increase in temperature to 39-42 degrees C. Malignant hyperthermia may occur in response to either inhalational anesthetics such as halothane, to muscle relaxants such as succinylcholine, or to exercise.

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Abnormality of metabolism/homeostasis
- Malignant hyperthermia
Abnormality of the musculoskeletal system
Abnormality of the nervous system
Constitutional symptom
- Myalgia

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVBrody myopathy

Qualitative or quantitative defects of protein SERCA1
- Brody myopathy

Follow this link to review classifications for Brody myopathy in Orphanet.

Recent clinical studies

Etiology

Clinical, morphological and genetic characterization of Brody disease: an international study of 40 patients.

Molenaar JP, Verhoeven JI, Rodenburg RJ, Kamsteeg EJ, Erasmus CE, Vicart S, Behin A, Bassez G, Magot A, Péréon Y, Brandom BW, Guglielmi V, Vattemi G, Chevessier F, Mathieu J, Franques J, Suetterlin K, Hanna MG, Guyant-Marechal L, Snoeck MM, Roberts ME, Kuntzer T, Fernandez-Torron R, Martínez-Arroyo A, Seeger J, Kusters B, Treves S, van Engelen BG, Eymard B, Voermans NC, Sternberg D
Brain 2020 Feb 1;143(2):452-466. doi: 10.1093/brain/awz410. PMID: 32040565 Free PMC Article

Flat Anterior Chamber after Trabeculectomy in Secondary Angle-Closure Glaucoma with BEST1 Gene Mutation: Case Series.

Zhong Y, Guo X, Xiao H, Luo J, Zuo C, Huang X, Huang J, Mi L, Zhang Q, Liu X
PLoS One 2017;12(1):e0169395. Epub 2017 Jan 5 doi: 10.1371/journal.pone.0169395. PMID: 28056057 Free PMC Article

Atypical nuclear abnormalities in a patient with Brody disease.

Mussini JM, Magot A, Hantaï D, Sternberg D, Chevessier F, Péréon Y
Neuromuscul Disord 2015 Oct;25(10):773-9. Epub 2015 Jul 13 doi: 10.1016/j.nmd.2015.07.005. PMID: 26248958

See all (3)

Diagnosis

Brody Disease, an Early-Onset Myopathy With Delayed Relaxation and Abnormal Gait: A Case Series of 9 Children.

Verhoeven JI, Kramer J, Seeger J, Molenaar JP, Braakman H, Kamsteeg EJ, Rodenburg RJ, Kusters B, Koudijs S, Van Engelen BG, Erasmus CE, Voermans NC
Neurology 2024 Mar 12;102(5):e209164. Epub 2024 Feb 19 doi: 10.1212/WNL.0000000000209164. PMID: 38373275

Clinical, morphological and genetic characterization of Brody disease: an international study of 40 patients.

Brody myopathy demonstrates a pseudo-increment on repetitive nerve stimulation.

Masingue M, Arzel M, Sternberg D, Stojkovic T, Behin A, Bassez G, Vicart S, Péréon Y, Magot A, Kuntzer T, Eymard B, Fournier E
Muscle Nerve 2020 Apr;61(4):491-495. Epub 2020 Jan 22 doi: 10.1002/mus.26809. PMID: 31944327

Brody disease: when myotonia is not myotonia.

Braz L, Soares-Dos-Reis R, Seabra M, Silveira F, Guimarães J
Pract Neurol 2019 Oct;19(5):417-419. Epub 2019 Apr 17 doi: 10.1136/practneurol-2019-002224. PMID: 30996034

Brody syndrome: a clinically heterogeneous entity distinct from Brody disease: a review of literature and a cross-sectional clinical study in 17 patients.

Voermans NC, Laan AE, Oosterhof A, van Kuppevelt TH, Drost G, Lammens M, Kamsteeg EJ, Scotton C, Gualandi F, Guglielmi V, van den Heuvel L, Vattemi G, van Engelen BG
Neuromuscul Disord 2012 Nov;22(11):944-54. Epub 2012 Jun 15 doi: 10.1016/j.nmd.2012.03.012. PMID: 22704959

See all (6)

Prognosis

Identification of a pathogenic mutation in ATP2A1 via in silico analysis of exome data for cryptic aberrant splice sites.

Bruels CC, Li C, Mendoza T, Khan J, Reddy HM, Estrella EA, Ghosh PS, Darras BT, Lidov HGW, Pacak CA, Kunkel LM, Modave F, Draper I, Kang PB
Mol Genet Genomic Med 2019 Mar;7(3):e552. Epub 2019 Jan 28 doi: 10.1002/mgg3.552. PMID: 30688039 Free PMC Article

Atypical nuclear abnormalities in a patient with Brody disease.

Mussini JM, Magot A, Hantaï D, Sternberg D, Chevessier F, Péréon Y
Neuromuscul Disord 2015 Oct;25(10):773-9. Epub 2015 Jul 13 doi: 10.1016/j.nmd.2015.07.005. PMID: 26248958

See all (2)

Clinical prediction guides

Clinical, morphological and genetic characterization of Brody disease: an international study of 40 patients.

Identification of a pathogenic mutation in ATP2A1 via in silico analysis of exome data for cryptic aberrant splice sites.

Flat Anterior Chamber after Trabeculectomy in Secondary Angle-Closure Glaucoma with BEST1 Gene Mutation: Case Series.

Zhong Y, Guo X, Xiao H, Luo J, Zuo C, Huang X, Huang J, Mi L, Zhang Q, Liu X
PLoS One 2017;12(1):e0169395. Epub 2017 Jan 5 doi: 10.1371/journal.pone.0169395. PMID: 28056057 Free PMC Article

SERCA1 protein expression in muscle of patients with Brody disease and Brody syndrome and in cultured human muscle fibers.

Guglielmi V, Vattemi G, Gualandi F, Voermans NC, Marini M, Scotton C, Pegoraro E, Oosterhof A, Kósa M, Zádor E, Valente EM, De Grandis D, Neri M, Codemo V, Novelli A, van Kuppevelt TH, Dallapiccola B, van Engelen BG, Ferlini A, Tomelleri G
Mol Genet Metab 2013 Sep-Oct;110(1-2):162-9. Epub 2013 Jul 20 doi: 10.1016/j.ymgme.2013.07.015. PMID: 23911890

Identification of a missense mutation in the bovine ATP2A1 gene in congenital pseudomyotonia of Chianina cattle: an animal model of human Brody disease.

Drögemüller C, Drögemüller M, Leeb T, Mascarello F, Testoni S, Rossi M, Gentile A, Damiani E, Sacchetto R
Genomics 2008 Dec;92(6):474-7. Epub 2008 Sep 25 doi: 10.1016/j.ygeno.2008.07.014. PMID: 18786632

See all (5)

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Brody myopathy(BROD)

Definition

Additional description

Clinical features

Term Hierarchy

Recent clinical studies

Etiology

Diagnosis

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Molecular resources

Consumer resources

Reviews

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