illandchill

NOTE: I am not a medical professional, nor am I providing medical advice. This is purely educational and is intended to help patients or caregivers find information on rare types of Ehlers-Danlos syndrome and rare gene variants that can then, for example, be given to medical professionals to aid in their care.

In literature, this type of EDS is often used interchangeably with the terms "Bethlem Myopathy 2," especially in the ClinVar database. ClinVar currently lists only 149 known pathogenic/likely pathogenic variants in the COL12A1 gene. On the other hand, there are 1,991 variants in the COL12A1 gene that are variants of uncertain significance.

Synonyms listed on the NORD website include: Bethlem myopathy 2, Bethlem myopathy caused by mutation in COL12A1, and myopathic Ehlers-Danlos Syndrome. I have also found that mEDS is often described as "Bethlem myopathy/Ehlers-Danlos overlap syndrome." Another condition that is typically grouped with mEDS (especially regarding COL12A1 variants) is Ullrich congenital muscular dystrophy type 2 (UCMD2); however, from what I can tell UCMD2 is a bit clinically different from mEDS (though it still has many similarities).

Bethlem Myopathy 2 is characterized by hypotonia (low muscle tone) and myopathy (disease of the muscle) at birth. Joint contractures, or when your joints and muscles tighten causing a deformity, can also occur alongside joint hypermobility. (OMIM)

Ullrich congenital muscle dystrophy-2 is characterized by joint hypermobility, joint contractures, and muscle weakness prior to walking. (OMIM)

Myopathic Ehlers-Danlos Syndrome is characterized by hypotonia and/or muscle weakness at birth, joint contractures, and joint hypermobility. It may also cause soft/doughy skin and atrophic scarring. (Orphanet)

Below is a list of papers published that relate to or directly mention COL12A1 variants, myopathic EDS, Bethlem Myopathy 2, and UCMD2. Articles that I know without a doubt are peer reviewed are marked with asterisks (*). Only five of these papers are not open-access and will require you to access them through this link. The papers are password protected, so please message me on here, on reddit, or email me at: illandchill@mailbox.org to gain access. Also, please message me on any of those places if you have found any papers not listed here. Please also let me know if any of these links break.

Lots of love, V.

Papers

Ehlers-Danlos/myopathy overlap syndrome caused by a large de novo deletion in COL12A1 *

Mutations in the collagen XII gene define a new form of extracellular matrix-related myopathy * - not open access

A novel COL12A1 variant expands the clinical picture of congenital myopathies with extracellular matrix defects *

Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice *

Novel defects in collagen XII and VI expand the mixed myopathy/Ehlers-Danlos syndrome and lead to variant-specific alterations in the extracellular matrix *

Collagen XII myopathy with rectus femoris atrophy and collagen XII retention in fibroblasts * - not open access

Dominant collagen XII mutations cause a distal myopathy *

COL12A1 Gene Variant and a Review of the Literature: A Case Report of Ullrich Congenital Muscular Dystrophy *

Homozygous splice site variant affecting the first von Willebrand factor A domain of COL12A1 in a patient with myopathic Ehlers-Danlos syndrome *

A novel homozygous nonsense variant in COL12A1 causes myopathic Ehlers-Danlos syndrome: A case report and literature review * - not open access

Whole exome sequencing identifies a novel variant in the COL12A1 gene in a family with Ullrich congenital muscular dystrophy 2 * - not open access

Ehlers-Danlos: A Literature Review and Case Report in a Colombian Woman with Multiple Comorbidities *

Clinical characterization of Collagen XII-related disease caused by biallelic COL12A1 variants *

COL12A1-related myopathic Ehlers-Danlos syndrome with Chiari I malformation: A clinical report *

Ullrich congenital muscular dystrophy: Connective tissue abnormalities in the skin support overlap with Ehlers-Danlos syndromes *

The Ehlers-Danlos Syndromes against the Backdrop of Inborn Errors of Metabolism *

The Ehlers-Danlos syndromes, rare types

Myopathic Ehlers-Danlos Syndrome (mEDS) Related to COL12A1: Two Novel Families and Literature Review *

Recessive COL12A1 loss of function EDS/myopathy overlap syndrome: confirmation and expansion of a consistently severe phenotype *

Collagen type XII: A new congenital matrix and muscle disease * - not open access

A Novel COL12A1 Mutation Causes Oral Tissue Abnormalities by Regulating Gingival Fibroblast Function *

Collagen XII as a new disease gene for Bethlem-like myopathy *

Collagen XII-Related Myopathy: An Emerging Spectrum of Extracellular Matrix-Related Myopathy *