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Ehlers-Danlos syndrome

From SNPedia

Ehlers–Danlos syndrome (EDS) is an inherited connective tissue disorder with different presentations that have been classified into several primary types. EDS is caused by a defect in the structure, production, or processing of collagen or proteins that interact with collagen, such as mutations in the COL5A or COL3A genes. More specifically, as outlined in Wikipedia the EDS types and corresponding genes are as follows:

Name Number Description Gene(s)
Hypermobility type 3 Affects 1 in 10,000 to 15,000 and is caused by an autosomal dominant or autosomal recessive mechanism. Mutations in either of two separate genes (which are also involved in Vascular EDS and Tenascin-X deficiency EDS, respectively) may lead to this variant. However, there has only been one report involving one family showing this mutation in COL3A1 (10.1093/hmg/3.9.1617), while there is some thought that the TNXB related EDS is actually its own separate subtype apart from type III. Joint hypermobility is the hallmark of this type, with less severe skin manifestations. Joint instability and chronic musculoskeletal pain are particularly prominent in this type. Patients with the Hypermobility Type experience frequent joint Joint dislocation|dislocations and subluxations (partial/incomplete dislocations), with or without trauma. As a result, pain is a common, severe, and a lifelong symptom of this type. Additionally, osteoarthritis is common, and many get it earlier in life than expected. TNXB, SometimesCOL3A1 (see description).
Classical types 1 & 2 Affects approximately 1 in 20,000 to 50,000 people. It is caused by autosomal dominant mechanism and affects type-V collagen, as well as type-I collagen. Type 1 typically presents with severe skin involvement, and type 2 presents with mild to moderate skin involvement. Patients with the Classical Type may experience the same symptoms as the Hypermobility Type. The main difference between the Hypermobility and Classical Types are the Classical has more skin involvement while the Hypermobility Type has more joint involvement. Those with Classical EDS can also have severe joints issues like those with the Hypermobility Type. COL5A1, COL5A2, COL1A1
Vascular type 4 Is an autosomal dominant defect in the type-III collagen synthesis; now thought to affect approximately 1 in 50,000 to 1 in 200,000. Most are only diagnosed after rupturing, so it is believed that many more may well go undiagnosed. The vascular type is considered one of the more serious forms of Ehlers–Danlos syndrome because blood vessels and organs are fragile and prone to tearing (rupture). Many patients with EDS type 4 express a characteristic facial appearance (large eyes, small chin, sunken cheeks, thin nose and lips, lobeless ears), have a small stature with a slim build, and typically have thin, pale, translucent skin (veins can usually be seen on the chest and abdomen) with very easy bruising and propensity to develop ecchymoses (bruising without trauma). Degree of severity depends on the nature of the mutations involved. The current statistics, based largely on those only diagnosed after rupturing, indicate that about one in four people diagnosed with vascular type EDS develop a significant health problem by age 20 and more than 80 percent develop life-threatening complications by age 40. COL3A1
Kyphoscoliosis type 6 Is an autosomal recessive defect due to deficiency of an enzyme called lysyl hydroxylase; it is very rare, with fewer than 60 cases reported. The kyphoscoliosis type is characterized by progressive curvature of the spine (scoliosis), thin conjunctiva with blue appearing sclera (eyes) and severe muscle weakness. PLOD1
Arthrochalasia types 7A & B Is an autosomal dominant defect which is very rare, with roughly 30 cases reported. It affects type-I collagen. The arthrochalasia type is characterised by very loose joints and dislocations involving both hips. Their joints are much looser than the Hypermobility Type. It could be considered more severe than Hypermobility Type. COL1A1, COL1A2
Dermatosparaxis type 7C Autosomal recessive. Very rare, with approximately 10 cases reported. The dermatosparaxis type is characterized by extremely fragile and sagging skin. ADAMTS2

And these genes are mentioned in Wikipedia: COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, and TNXB

Coverage (% of known variants of any magnitude in SNPedia tested by a given company/chip) for variants from the genes mentioned above is shown in the following table:

SNP % is based on # of SNPs on chip vs in SNPedia (unadjusted for mutation frequency or magnitude)
Company & chip version TNXB COL1A1 COL5A1 COL5A2 COL3A1 PLOD1 COL1A2 ADAMTS2
23andMe v5 19% 41% 50% 47% 23% 12% 31% 43%
Ancestry v2
28% 37% 12% 5% 66% 29% 38% 71%

rs28937869 is linked in OMIM

[PMID 29606302] Bi-allelic Alterations in AEBP1 Lead to Defective Collagen Assembly and Connective Tissue Structure Resulting in a Variant of Ehlers-Danlos Syndrome