Types of Ehlers-Danlos Syndromes (EDS)

By Afsaneh Khetrapal, BScReviewed by Benedette Cuffari, M.Sc.

There are many types of Ehlers-Danlos syndromes (EDS).

Based on the inheritance pattern, EDS can be classified as autosomal dominant, autosomal recessive, and autosomal dominant or recessive. In each of these types, a set of major and minor criteria is identified and a minimal criterion is arrived at for the physicians to suggest the EDS types. Molecular testing is typically used to confirm the final diagnosis.

Autosomal dominant EDS

Below are the types of EDS that develop due to an autosomal dominant inheritance pattern:

• Classical
• Vascular
• Hypermobile
• Arthrochalasia
• Periodontal

The two major criteria for Classical EDS (cEDS) include atrophic scarring and hyperextensibility of the skin, as well as generalized joint hypermobility (GJH). When these two major criteria, or the first major criterion in combination with a minimum of three minor criteria (out of 9 minor criteria), is present, cEDS is suggested as the appropriate diagnosis.

The heterozygous mutation of the gene COL3A1 causes Vascular EDS (vEDS). Testing is considered when there is a family history of the disorder. Additionally, the presence of a few major criteria, out of the 5, combined with few other minor criteria, out of 12, will confirm the presence of vEDS.

There is no sufficient data established as criteria to diagnose Hypermobile EDS (hEDS), whereas three major and five minor criteria are established for Arthrochalasia EDS (aEDS). Diagnosis is suggested when major criteria 1 & 3 are present, or when major criterion 2 combines with a minimum of two minor criteria.

When the C1R gene is absent or a C1S gene mutations exists, Periodontal EDS (pEDS) is likely the appropriate diagnosis.

Autosomal recessive

Autosomal recessive inheritance results in the following types of EDS:

• Classical-like
• Cardiac-valvular
• Dermatosparaxis
• Kyphoscoliotic
• Brittle Cornea Syndrome
• Spondylodysplastic
• Musculocontractural

Classical-like EDS (clEDS) is caused by the absence of Tenascin XB, which is the only gene related with clEDS. Although seven minor criteria are identified, physicians will only suggest clEDS when all three major criteria are present, along with an autosomal recessive inheritance family history.

Cardiac-valvular EDS (cvEDS) is caused by biallelic mutations of the gene COL1A2, which is the only gene related to cvEDS. The diagnosis for this type of EDS occurs when there is a family history of autosomal recessive type combined with the first major criterion and either one other major criterion or a minimum of two minor criteria.

With 9 major and 11 minor criteria defined, Dermatosparaxis EDS (dEDS) is suggested when there is extreme fragility of the skin and distinctive craniofacial features. These are two major criteria that must be present for a dEDS diagnosis, along with either one major criterion or three minor criteria. The only gene connected with dEDS is ADAMTS2 and its biallelic mutations result in dEDS.

Kyphoscoliotic EDS (kEDS) is suggested when the first two major criteria are present, along with either the third major criteria or three general or gene-related criteria. Mutations of the genes PLOD1 or FKBP14 result in kEDS.

Brittle Cornea Syndrome (BCS) is due to the biallelic mutations of either ZNF469 gene or PRDM5 gene. Diagnosis is recommended when the first major criteria of a thin cornea with a thickness of central corneal less than 400 µm without rupture or sometimes ruptured is present along with one more major criteria. The major criteria that can support a BCS diagnosis include an early start of keratoconus, the early beginning of keratoglobus that are progressive, and blue sclera. A diagnosis of BCS can also be achieved when first major criterion combines with any 3 of the 14 minor criteria.

For Spondylodysplastic EDS (spEDS), three major, five minor, and specific criteria related to genes B4GALT7, B3GALT6, and SLC39A13 are identified. Diagnosis is suggested when the first two major criteria, distinctive radiographic abnormalities, are present in combination with a minimum of three minor criteria that are either general or specific to the gene.

Biallelic mutations of the gene CHST14 are responsible for Musculocontractural EDS (mcEDS). Though 15 minor criteria are defined, suggestion for this type of EDS is based on the identified three major criteria. When the first two major criteria are present in the individual at birth, during early childhood, or when the first and third major criteria are present in adolescents and adults, mcEDS is suggested.

Autosomal dominant or recessive

Myopathic EDS (mEDS) is either autosomal dominant or recessive. Biallelic mutations of the gene COL12A1 are the cause of this type of EDS, in which Type XII Collagen protein is involved. With three major and four minor criteria defined, physicians suggest a diagnosis if the first major criterion is present with either one other major criterion or three minor criteria.

EDS Groups

Based on the similarities of the EDS causing genes affecting the human body, EDS can also be grouped as:

References

• https://ehlers-danlos.com/eds-types/
• https://rarediseases.info.nih.gov/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180581/
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548259/

Further Reading

• All Ehlers-Danlos Syndrome Content
• What is Ehlers-Danlos Syndrome?
• Living with Ehlers-Danlos Syndrome