11/17/2025
Good EDS info
The Ehlers-Danlos syndromes (EDS) are a group of 13 heritable connective tissue disorders, each caused by specific gene variants that affect the structure or processing of collagen and related proteins. These genetic changes weaken connective tissues throughout the body, leading to symptoms like joint hypermobility, skin hyperextensibility, and tissue fragility.
Genetic Basis of EDS Subtypes: With the exception of hypermobile EDS (hEDS), all EDS subtypes have an identified genetic cause that can be confirmed by molecular genetic testing. The inheritance patterns are typically autosomal dominant (AD) or autosomal recessive (AR). An autosomal dominant condition only requires one copy of the altered gene to cause the trait or disorder, with affected individuals having a 50% chance of passing it to each child. An autosomal recessive condition requires two copies of the altered gene (one from each parent) to manifest, meaning affected individuals typically have parents who are both carriers but do not show symptoms themselves
* The Ehlers-Danlos syndromes:
EDS Subtype: Classical (cEDS) Gene(s) Involved : COL5A1, COL5A2, rarely COL1A1. Inheritance Pattern : AD. Affected Protein/Process: Type V collagen (structure/production).
EDS Subtype: Classical-like 1 (clEDS). Gene(s) Involved : TNXB. Inheritance Pattern: AR . Affected Protein/Process: Tenascin XB (ECM interaction).
EDS Subtype: Vascular (vEDS). Gene(s) Involved : COL3A1, rarely COL1A1. Inheritance Pattern : AD. Affected Protein/Process: Type III collagen (processing/secretion).
EDS Subtype: Hypermobile (hEDS). Gene(s) Involved: Unknown. Inheritance Pattern: AD. (suspected). Affected Protein/Process: Cause unknown.
EDS Subtype: Arthrochalasia (aEDS). Gene(s) Involved: COL1A1, COL1A2. Inheritance Pattern: AD. Affected Protein/Process: Type I collagen (N-propeptide cleavage).
EDS Subtype: Kyphoscoliotic (kEDS). Gene(s) Involved: PLOD1, FKBP14. Inheritance Pattern: AR. Affected Protein/Process: Lysyl hydroxylase 1 or a protein involved in collagen folding.
EDS Subtype: Dermatosparaxis (dEDS) Gene(s) Involved : ADAMTS2. Inheritance Pattern: AR. Affected Protein/Process: Procollagen N-peptidase (cleavage of propeptides).
EDS Subtype: Cardiac-valvular (cvEDS). Gene(s) Involved: COL1A2. Inheritance Pattern: AR. Affected Protein/Process: Type I collagen.
EDS Subtype: Brittle Cornea Syndrome (BCS) . Gene(s) Involved: ZNF469, PRDM5. Inheritance Pattern: AR. Affected Protein/Process: Transcription regulation of collagens.
EDS Subtype: Spondylodysplastic (spEDS). Gene(s) Involved : B4GALT7, B3GALT6, SLC39A13. Inheritance Pattern: AR. Affected Protein/Process: Glycosaminoglycan biosynthesis or zinc transport.
EDS Subtype: Musculocontractural (mcEDS). Gene(s) Involved: CHST14, DSE. Inheritance Pattern: AR. Affected Protein/Process: Dermatan sulfate biosynthesis.
EDS Subtype: Myopathic (mEDS) Gene(s) Involved: COL12A1. Inheritance Pattern: AD or AR. Affected Protein/Process: Type XII collagen.
EDS Subtype: Periodontal (pEDS) Gene(s) Involved: C1R, C1SCHST14, DSE AR Dermatan sulfate biosynthesis. Inheritance Pattern: AD. Affected Protein/Process: Complement components (collagen degradation)
Collagen Defects: The primary issue in most types of EDS is a defect in collagen synthesis, processing, or structure, which compromises the strength and integrity of connective tissues throughout the body.
Inheritance: The specific inheritance pattern (autosomal dominant or recessive) depends on the subtype, meaning some cases can be passed on from a single parent and others require variants from both parents.
De Novo Mutations: In some instances, the genetic change is not inherited from a parent but occurs spontaneously (de novo) in the affected individual.
Diagnosis: Diagnosis is primarily clinical, especially for hEDS where no genetic marker has been found. For all other types, genetic testing is used to confirm the diagnosis and rule out other conditions like Marfan syndrome or osteogenesis imperfecta.
Variable Severity: Even within the same family and the same EDS type, symptoms can vary significantly in severity.
Genetic Testing: Genetic testing can confirm the diagnosis for all subtypes except hEDS. For the hypermobile type, diagnosis is based solely on clinical criteria due to the unknown genetic cause.