U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Bethlem myopathy(BTHLM1; BTHLM1A)

MedGen UID:
331805
Concept ID:
C1834674
Disease or Syndrome
Synonyms: Benign Congenital Muscular Dystrophy; Benign Congenital Myopathy with Contractures; Muscular dystrophy, benign congenital; Myopathy, benign congenital, with contractures
SNOMED CT: Bethlem myopathy (718572004); Benign autosomal dominant myopathy (718572004)
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.
 
Related genes: COL12A1, COL6A3, COL6A2, COL6A1
 
Monarch Initiative: MONDO:0008029
OMIM®: 120220; 158810
OMIM® Phenotypic series: PS158810
Orphanet: ORPHA610

Definition

Bethlem myopathy-1 (BTHLM1) is a congenital muscular dystrophy characterized by distal joint laxity and a combination of distal and proximal joint contractures. The age at onset is highly variable, ranging from infancy to adulthood. Disease progression is slow and ambulation is usually retained into adulthood (summary by Butterfield et al., 2013). Genetic Heterogeneity of Bethlem Myopathy See Bethlem myopathy-1B (BTHLM1B; 620725), caused by mutation in the COL6A2 gene (120240) on chromosome 21q22; Bethlem myopathy-1C (620726), caused by mutation the COL6A3 gene (120250) on chromosome 2q37; and Bethlem myopathy-2 (BTHLM2; 616471), caused by mutation in the COL12A1 gene (120320) on chromosome 6q13-q14. [from OMIM]

Additional description

From MedlinePlus Genetics
Individuals with collagen VI-related dystrophy often have signs and symptoms of multiple forms of this condition, so it can be difficult to assign a specific diagnosis. The overlap in disease features, in addition to their common cause, is why these once separate conditions are now considered part of the same disease spectrum.

People with Ullrich congenital muscular dystrophy have severe muscle weakness beginning soon after birth. Some affected individuals are never able to walk and others can walk only with support. Those who can walk often lose the ability, usually in early adolescence. Individuals with Ullrich congenital muscular dystrophy develop contractures in their shoulders, elbows, hips, and knees, which further impair movement. Many individuals with this form of the condition have loose joints (joint laxity) in the fingers, wrists, toes, ankles, and other joints. Affected individuals need continuous mechanical ventilation to help them breathe while sleeping, and some may need it in the daytime. As in Bethlem muscular dystrophy, some people with Ullrich congenital muscular dystrophy have follicular hyperkeratosis; soft, velvety skin on the palms and soles; and abnormal wound healing.

The intermediate form of collagen VI-related dystrophy is characterized by muscle weakness that begins in infancy. Affected children are able to walk, although walking becomes increasingly difficult starting in early adulthood. They develop contractures in their fingers, elbows, shoulders, and ankles in childhood. In some affected people, the respiratory muscles are weakened, requiring people to use a machine to help them breathe (mechanical ventilation), particularly during sleep.

People with Bethlem muscular dystrophy usually have low muscle tone (hypotonia) in infancy. Muscle weakness can begin at any age but often appears in childhood to early adulthood. The muscle weakness is slowly progressive, with about two-thirds of affected individuals over age 50 needing walking assistance, particularly when outdoors. Affected individuals usually develop contractures by adulthood, typically in their fingers, elbows, shoulders, and ankles. Older individuals may develop weakness in respiratory muscles, which can cause breathing problems. Some people with this mild form of collagen VI-related dystrophy have skin abnormalities, including small bumps called follicular hyperkeratosis on the arms and legs; soft, velvety skin on the palms of the hands and soles of the feet; and abnormal wound healing that creates shallow scars.

Collagen VI-related dystrophy is a group of disorders that affect skeletal muscles (which are the muscles used for movement) and connective tissue (which provides strength and flexibility to the skin, joints, and other structures throughout the body). Most affected individuals have muscle weakness and joint deformities called contractures that restrict movement of the affected joints and worsen over time. Researchers have described several forms of collagen VI-related dystrophy, which range in severity: Bethlem muscular dystrophy is the mildest, an intermediate form is moderate in severity, and Ullrich congenital muscular dystrophy is the most severe.  https://medlineplus.gov/genetics/condition/collagen-vi-related-myopathy

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Macroscopic hematuria
MedGen UID:
633103
Concept ID:
C0473237
Finding
Hematuria that is visible upon inspection of the urine.
Ankle contracture
MedGen UID:
575402
Concept ID:
C0343148
Acquired Abnormality
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Knee contracture
MedGen UID:
332406
Concept ID:
C1837263
Anatomical Abnormality
Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the knee joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.
Shoulder girdle muscle atrophy
MedGen UID:
339837
Concept ID:
C1847766
Finding
Amyotrophy affecting the muscles of the shoulder girdle.
Limb-girdle muscle weakness
MedGen UID:
347625
Concept ID:
C1858127
Finding
Weakness of the limb-girdle muscles (also known as the pelvic and shoulder girdles), that is, lack of strength of the muscles around the shoulders and the pelvis.
Abnormality of the cardiovascular system
MedGen UID:
116727
Concept ID:
C0243050
Congenital Abnormality
Any abnormality of the cardiovascular system.
Abnormal EKG
MedGen UID:
105507
Concept ID:
C0522055
Finding
Abnormal rhythm of the heart.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Tip-toe gait
MedGen UID:
98104
Concept ID:
C0427144
Finding
An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Abnormal nerve conduction velocity
MedGen UID:
355800
Concept ID:
C1866772
Finding
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Abnormal cranial nerve physiology
MedGen UID:
1671020
Concept ID:
C4732756
Pathologic Function
A functional abnormality affecting one or more of the cranial nerves, which emerge directly from the brain stem.
Congenital hip dislocation
MedGen UID:
9258
Concept ID:
C0019555
Disease or Syndrome
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Difficulty climbing stairs
MedGen UID:
68676
Concept ID:
C0239067
Finding
Reduced ability to climb stairs.
Neck muscle weakness
MedGen UID:
66808
Concept ID:
C0240479
Finding
Decreased strength of the neck musculature.
Finger joint contracture
MedGen UID:
575400
Concept ID:
C0343146
Acquired Abnormality
Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of a finger joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.
Camptodactyly of finger
MedGen UID:
98041
Concept ID:
C0409348
Finding
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers cannot be extended to 180 degrees by either active or passive extension.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Difficulty running
MedGen UID:
108251
Concept ID:
C0560346
Finding
Reduced ability to run.
Elbow contracture
MedGen UID:
331445
Concept ID:
C1833142
Anatomical Abnormality
A limitation in the passive range of motion of the elbow resulting from loss of elasticity in the periarticular tissues owing to structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules or skin.
Distal lower limb amyotrophy
MedGen UID:
324515
Concept ID:
C1836451
Disease or Syndrome
Muscular atrophy of distal leg muscles.
Centrally nucleated skeletal muscle fibers
MedGen UID:
330782
Concept ID:
C1842170
Finding
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
Axial muscle weakness
MedGen UID:
334472
Concept ID:
C1843697
Finding
Reduced strength of the axial musculature (i.e., of the muscles of the head and neck, spine, and ribs).
Muscle fiber necrosis
MedGen UID:
376893
Concept ID:
C1850848
Pathologic Function
Abnormal cell death involving muscle fibers usually associated with break in, or absence of, muscle surface fiber membrane and resulting in irreversible damage to muscle fibers.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Fiber type grouping
MedGen UID:
478824
Concept ID:
C3277194
Finding
An abnormal distribution of muscle fiber types in muscle tissue. Human skeletal muscle contains at least two fiber types recognizable by histochemical techniques. In transverse sections of normal skeletal muscle, type 1 and type 2 fibers are distributed in a random fashion. Grouping of fibers of the same type can be seen in certain peripheral neuropathies, thought to be due to reinnervation of denervated muscle fibers by sprouting axons. With grouping, motor units enlarge. The fibers of a motor unit, which are normally scattered, come to lie adjacent to one another. Histochemical examination shows groups of muscle fibers of the same histochemical type.
Fatty replacement of skeletal muscle
MedGen UID:
866735
Concept ID:
C4021082
Finding
Muscle fibers degeneration resulting in fatty replacement of skeletal muscle fibers
EMG: myopathic abnormalities
MedGen UID:
867362
Concept ID:
C4021726
Pathologic Function
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding
Skin rash
MedGen UID:
1830322
Concept ID:
C5779628
Sign or Symptom
A red eruption of the skin.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Mildly elevated creatine kinase
MedGen UID:
342469
Concept ID:
C1850309
Finding
Congenital muscular torticollis
MedGen UID:
86902
Concept ID:
C0079352
Congenital Abnormality
A congenital form of torticollis resulting from shortening of the sternocleidomastoid muscle and leading to a limited range of motion in both rotation and lateral bending.
Keratosis pilaris
MedGen UID:
82664
Concept ID:
C0263383
Disease or Syndrome
An anomaly of the hair follicles of the skin that typically presents as small, rough, brown folliculocentric papules distributed over characteristic areas of the skin, particularly the outer-upper arms and thighs.
Phrynoderma
MedGen UID:
83101
Concept ID:
C0334013
Disease or Syndrome
A skin condition characterized by excessive development of keratin in hair follicles, resulting in rough, cone-shaped, elevated papules resulting from closure of hair follicles with a white plug of sebum.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Bethlem myopathy in Orphanet.

Professional guidelines

PubMed

Kwong AK, Zhang Y, Ho RS, Gao Y, Ling X, Tsang MH, Luk HM, Chung BH, Bönnemann CG, Javed A, Chan SH
Neuromuscul Disord 2023 May;33(5):371-381. Epub 2023 Mar 12 doi: 10.1016/j.nmd.2023.03.003. PMID: 37023487
Voermans NC, Bonnemann CG, Hamel BC, Jungbluth H, van Engelen BG
J Neurol 2009 Jan;256(1):13-27. Epub 2009 Feb 9 doi: 10.1007/s00415-009-0105-1. PMID: 19221853

Recent clinical studies

Etiology

Caria F, Cescon M, Gualandi F, Pichiecchio A, Rossi R, Rimessi P, Cotti Piccinelli S, Gallo Cassarino S, Gregorio I, Galvagni A, Ferlini A, Padovani A, Bonaldo P, Filosto M
Neuromuscul Disord 2019 Sep;29(9):657-663. Epub 2019 Jul 30 doi: 10.1016/j.nmd.2019.07.007. PMID: 31471117
Panadés-de Oliveira L, Rodríguez-López C, Cantero Montenegro D, Marcos Toledano MDM, Fernández-Marmiesse A, Esteban Pérez J, Hernández Lain A, Domínguez-González C
J Neurol 2019 Apr;266(4):934-941. Epub 2019 Jan 31 doi: 10.1007/s00415-019-09217-z. PMID: 30706156
Kim SY, Kim WJ, Kim H, Choi SA, Lee JS, Cho A, Jang SS, Lim BC, Kim KJ, Kim JI, Hahn SH, Chae JH
Muscle Nerve 2018 Sep;58(3):381-388. doi: 10.1002/mus.26093. PMID: 29406609
Sframeli M, Sarkozy A, Bertoli M, Astrea G, Hudson J, Scoto M, Mein R, Yau M, Phadke R, Feng L, Sewry C, Fen ANS, Longman C, McCullagh G, Straub V, Robb S, Manzur A, Bushby K, Muntoni F
Neuromuscul Disord 2017 Sep;27(9):793-803. Epub 2017 Jun 16 doi: 10.1016/j.nmd.2017.06.008. PMID: 28688748
Voermans NC, Bonnemann CG, Hamel BC, Jungbluth H, van Engelen BG
J Neurol 2009 Jan;256(1):13-27. Epub 2009 Feb 9 doi: 10.1007/s00415-009-0105-1. PMID: 19221853

Diagnosis

Jfri A, Alajmi A
Dermatology 2018;234(3-4):127-130. Epub 2018 Aug 16 doi: 10.1159/000491924. PMID: 30114700
Sframeli M, Sarkozy A, Bertoli M, Astrea G, Hudson J, Scoto M, Mein R, Yau M, Phadke R, Feng L, Sewry C, Fen ANS, Longman C, McCullagh G, Straub V, Robb S, Manzur A, Bushby K, Muntoni F
Neuromuscul Disord 2017 Sep;27(9):793-803. Epub 2017 Jun 16 doi: 10.1016/j.nmd.2017.06.008. PMID: 28688748
Bushby KM, Collins J, Hicks D
Adv Exp Med Biol 2014;802:185-99. doi: 10.1007/978-94-007-7893-1_12. PMID: 24443028
Lampe AK, Bushby KM
J Med Genet 2005 Sep;42(9):673-85. doi: 10.1136/jmg.2002.002311. PMID: 16141002Free PMC Article
Bertini E, Pepe G
Eur J Paediatr Neurol 2002;6(4):193-8. doi: 10.1053/ejpn.2002.0593. PMID: 12374585

Therapy

Castagnaro S, Pellegrini C, Pellegrini M, Chrisam M, Sabatelli P, Toni S, Grumati P, Ripamonti C, Pratelli L, Maraldi NM, Cocchi D, Righi V, Faldini C, Sandri M, Bonaldo P, Merlini L
Autophagy 2016 Dec;12(12):2484-2495. Epub 2016 Sep 22 doi: 10.1080/15548627.2016.1231279. PMID: 27656840Free PMC Article
Sabatelli P, Palma E, Angelin A, Squarzoni S, Urciuolo A, Pellegrini C, Tiepolo T, Bonaldo P, Gualandi F, Merlini L, Bernardi P, Maraldi NM
J Cell Physiol 2012 Jul;227(7):2927-35. doi: 10.1002/jcp.23039. PMID: 21953374Free PMC Article
Bernardi P, Bonaldo P
Ann N Y Acad Sci 2008 Dec;1147:303-11. doi: 10.1196/annals.1427.009. PMID: 19076452
Merlini L, Bernardi P
Neurotherapeutics 2008 Oct;5(4):613-8. doi: 10.1016/j.nurt.2008.08.004. PMID: 19019314Free PMC Article
Hicks D, Lampe AK, Barresi R, Charlton R, Fiorillo C, Bonnemann CG, Hudson J, Sutton R, Lochmüller H, Straub V, Bushby K
Neurology 2008 Apr 1;70(14):1192-9. doi: 10.1212/01.wnl.0000307749.66438.6d. PMID: 18378883

Prognosis

Panadés-de Oliveira L, Rodríguez-López C, Cantero Montenegro D, Marcos Toledano MDM, Fernández-Marmiesse A, Esteban Pérez J, Hernández Lain A, Domínguez-González C
J Neurol 2019 Apr;266(4):934-941. Epub 2019 Jan 31 doi: 10.1007/s00415-019-09217-z. PMID: 30706156
Sframeli M, Sarkozy A, Bertoli M, Astrea G, Hudson J, Scoto M, Mein R, Yau M, Phadke R, Feng L, Sewry C, Fen ANS, Longman C, McCullagh G, Straub V, Robb S, Manzur A, Bushby K, Muntoni F
Neuromuscul Disord 2017 Sep;27(9):793-803. Epub 2017 Jun 16 doi: 10.1016/j.nmd.2017.06.008. PMID: 28688748
Finsterer J, Stöllberger C
Scand Cardiovasc J 2008 Feb;42(1):9-24. doi: 10.1080/14017430701854953. PMID: 18273731
van der Kooi AJ, de Voogt WG, Bertini E, Merlini L, Talim FB, Ben Yaou R, Urtziberea A, de Visser M
Arch Neurol 2006 Nov;63(11):1617-21. doi: 10.1001/archneur.63.11.1617. PMID: 17101832
Gordon ES, Hoffman EP
Curr Opin Neurol 2001 Oct;14(5):567-73. doi: 10.1097/00019052-200110000-00004. PMID: 11562567

Clinical prediction guides

Merlini L, Sabatelli P, Gualandi F, Redivo E, Di Martino A, Faldini C
Int J Mol Sci 2023 Aug 5;24(15) doi: 10.3390/ijms241512474. PMID: 37569848Free PMC Article
Kim SY, Kim WJ, Kim H, Choi SA, Lee JS, Cho A, Jang SS, Lim BC, Kim KJ, Kim JI, Hahn SH, Chae JH
Muscle Nerve 2018 Sep;58(3):381-388. doi: 10.1002/mus.26093. PMID: 29406609
Deconinck N, Richard P, Allamand V, Behin A, Lafôret P, Ferreiro A, de Becdelievre A, Ledeuil C, Gartioux C, Nelson I, Carlier RY, Carlier P, Wahbi K, Romero N, Zabot MT, Bouhour F, Tiffreau V, Lacour A, Eymard B, Stojkovic T
J Neurol Neurosurg Psychiatry 2015 Dec;86(12):1337-46. Epub 2014 Dec 22 doi: 10.1136/jnnp-2013-307245. PMID: 25535305
Voermans NC, Bonnemann CG, Hamel BC, Jungbluth H, van Engelen BG
J Neurol 2009 Jan;256(1):13-27. Epub 2009 Feb 9 doi: 10.1007/s00415-009-0105-1. PMID: 19221853
van der Kooi AJ, de Voogt WG, Bertini E, Merlini L, Talim FB, Ben Yaou R, Urtziberea A, de Visser M
Arch Neurol 2006 Nov;63(11):1617-21. doi: 10.1001/archneur.63.11.1617. PMID: 17101832

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...