Ehlers Danlos Syndrome (EDS) – 13 Subtypes, Interesting Facts, Symptoms, Prognosis

What is Ehlers Danlos Syndrome (EDS)

Ehlers Danlos Syndrome are a group of related disorders. The etiology of EDS is due to various genetic defects in the collagen.

Collagen is one of the major structural components of the body. 

Poor strength of collagen is responsible for the symptoms in patients with Ehlers Danlos Syndrome.

Synonyms

  • EDS
  • E-D Syndrome

Prevalence of EDS

The data from the Research shows that the total prevalence of the Ehlers-Danlos syndromes is 1 in 2,500 to 1 in 5,000 people.

Recent clinical evidence proves that Ehlers Danlos Syndrome may be more common.

The conditions affects both males and females of all racial and ethnic backgrounds.

Subtypes of Ehlers Danlos Syndrome

  1. Classic EDS
  2. Classical-like EDS
  3. Cardiac-valvular
  4. Vascular EDS
  5. Hypermobile EDS
  6. Arthrochalasia EDS
  7. Dermatosparaxis EDS
  8. Kyphoscoliotic EDS
  9. Brittle cornea syndrome
  10. Spondylodysplastic EDS
  11. Musculocontractural EDS
  12. Myopathic EDS
  13. Periodontal EDS

Symptoms of Classic EDS

Very Common Symptoms

  • Atrophic scars 
  • Cigarette-paper scars 
  • Fragile skin 
  • Generalized joint laxity 
  • Hyperextensible skin 
  • Soft, doughy skin 
  • Striae distensae 

Common Symptoms

  • Chronic constipation 
  • Fatigue 
  • Gastroesophageal reflux 
  • Muscle spasm 
  • Muscle weakness 
  • Muscular hypotonia 
  • Nausea 
  • Osteopenia 
  • Poor wound healing 
  • Pulp stones 
  • Vomiting 

Occasional Symptoms

  • Abnormal cornea morphology 
  • Abnormal heart valve physiology 
  • Abnormality of the foot 
  • Abnormality of the temporomandibular joint 
  • Acrocyanosis 
  • Aortic root aneurysm 
  • Arterial dissection 
  • Arterial rupture 
  • Arteriovenous fistula 
  • Arthralgia 
  • Bladder diverticulum 
  • Blepharochalasis 
  • Bruising susceptibility 
  • Cervical insufficiency 
  • Dermatochalasis 
  • Dilatation of the cerebral artery 
  • Dislocated radial head 
  • Ecchymosis 
  • Epicanthus 
  • Hiatus hernia 
  • Hip dislocation 
  • Incisional hernia 
  • Inguinal hernia 
  • Joint swelling 
  • Limb pain 
  • Molluscoid pseudotumors 
  • Motor delay 
  • Osteoarthritis 
  • Patellar dislocation 
  • Pes planus 
  • Phalangeal dislocation
  • Piezogenic pedal papules 
  • Premature birth 
  • Premature rupture of membranes 
  • Prematurely aged appearance 
  • Prolonged bleeding time 
  • Rectal prolapse 
  • Scoliosis 
  • Shoulder dislocation 
  • Subcutaneous spheroids 
  • Talipes equinovarus 
  • Umbilical hernia 
  • Uterine prolapse 

Rare Symptoms

  • Headache 
  • Mitral regurgitation 
  • Mitral valve prolapse 
  • Orthostatic hypotension 
  • Tricuspid valve prolapse

Symptoms of Hypermobile EDS

Very Common Symptoms

  • Abnormality of the foot 
  • Acrocyanosis 
  • Arthralgia 
  • Elbow dislocation 
  • Fatigue 
  • Hip dislocation 
  • Hyperextensible skin 
  • Joint dislocation 
  • Joint hyperflexibility 
  • Myalgia 
  • Sleep disturbance 
  • Vertigo 
  • Wormian bones 

Common Symptoms

  • Arrhythmia 
  • Constipation 
  • Decreased nerve conduction velocity 
  • Depressivity 
  • Malabsorption 
  • Migraine 
  • Nausea and vomiting 
  • Osteoarthritis 
  • Pes planus 
  • Soft skin 
  • Thin skin 

Ocasional Symptoms

  • Abnormal palate morphology 
  • Abnormality of the dentition 
  • Abnormality of the gingiva 
  • Abnormality of the menstrual cycle 
  • Abnormality of the wrist 
  • Anorectal anomaly 
  • Aplasia/Hypoplasia of the abdominal wall musculature 
  • Apnea 
  • Arterial dissection 
  • Atypical scarring of skin 
  • Cystocele 
  • Decreased fertility 
  • Dilatation of the ascending aorta 
  • Epicanthus 
  • Gastroesophageal reflux 
  • Gastrointestinal dysmotility 
  • Genital hernia 
  • Gingival overgrowth 
  • Gingivitis 
  • Inguinal hernia 
  • Keratoconjunctivitis sicca 
  • Keratoconus 
  • Limitation of joint mobility 
  • Microdontia 
  • Osteolysis 
  • Paresthesia 
  • Ptosis 
  • Scoliosis 
  • Subcutaneous nodule 
  • Tendon rupture 
  • Umbilical hernia 
  • Venous insufficiency

Symptoms of Brittle cornea syndrome

Very Common Symptoms

  • Corneal dystrophy 
  • Decreased corneal thickness 
  • High myopia 
  • Hyperextensible skin 
  • Keratoglobus 
  • Soft skin 

Common Symptoms

  • Abnormality of hair pigmentation 
  • Blue sclerae 
  • Bruising susceptibility 
  • Conductive hearing impairment 
  • Corneal scarring 
  • Gait disturbance 
  • Joint hyperflexibility 
  • Myalgia 
  • Osteoporosis 
  • Sensorineural hearing impairment 
  • Visual loss

Ocasional Symptoms

  • Abnormality of epiphysis morphology 
  • Abnormality of the dentition 
  • Arachnodactyly 
  • Camptodactyly 
  • Cleft palate 
  • Corneal erosion 
  • Glaucoma 
  • Hallux valgus 
  • Hernia 
  • Hip dysplasia 
  • Increased susceptibility to fractures 
  • Mitral valve prolapse 
  • Neonatal hypotonia 
  • Pes planus 
  • Pulmonic stenosis 
  • Retinal detachment 
  • Scoliosis 

Symptoms of Arthrochalasia Ehlers-Danlos syndrome

Very Common Symptoms

  • Abnormality of subcutaneous fat tissue 
  • Aphasia 
  • Avascular necrosis of the capital femoral epiphysis 
  • Coxa valga 
  • Coxa vara 
  • Dysphasia 
  • Echolalia 
  • Hip dislocation 
  • Hip dysplasia 
  • Hyperextensible skin 
  • Joint dislocation 
  • Joint hyperflexibility 
  • Joint stiffness 
  • Muscle flaccidity 
  • Muscular hypotonia 
  • Mutism 
  • Scarring 
  • Severe short stature 
  • Thin skin 

Common Symptoms

  • Depressed nasal bridge 
  • Epicanthus 
  • Hypertelorism 
  • Micrognathia 
  • Retrognathia 
  • Scoliosis 

Ocasional Symptoms

  • Femoral hernia 
  • Inguinal hernia 

Symptoms of Dermatosparaxis Ehlers-Danlos syndrome

Very Common Symptoms

  • Abnormal joint morphology 
  • Abnormality of subcutaneous fat tissue 
  • Aphasia 
  • Avascular necrosis of the capital femoral epiphysis 
  • Coxa valga 
  • Coxa vara 
  • Dysphasia 
  • Echolalia 
  • Esophagitis 
  • Excessive wrinkled skin 
  • Gastroesophageal reflux 
  • Hernia 
  • Hiatus hernia
  • Hip dislocation 
  • Hip dysplasia 
  • Hyperextensible skin
  • Joint dislocation
  • Joint hyperflexibility 
  • Joint stiffness 
  • Muscular hypotonia
  • Mutism 
  • Osteomalacia 
  • Osteopenia 
  • Osteoporosis 
  • Prolonged bleeding time
  • Rickets 
  • Scarring 
  • Severe short stature 
  • Thin skin

Common Symptoms

  • Depressed nasal bridge 
  • Epicanthus
  • Femoral hernia 
  • Inguinal hernia 
  • Micrognathia 
  • Retrognathia 
  • Scoliosis

What is the diagnosis of EDS?

The crucial aspect to treat EDS is the timely diagnosis which is very important because of the very fact that though this condition cannot be cured completely, they are fully treatable.

  1. Classic EDS – molecular testing detects the genes encoding type V collagen (COL5A1 and COL5A2), the mutation of which is responsible for the Classic EDS
  2. Classical-like EDS – molecular testing detects the Tenascin XB gene, which is the only gene associated with Classical-like EDS.
  3. Cardiac-valvular – molecular testing detects the COL1A2 gene.
  4. Vascular EDS – molecular testing detects the COL3A1 gene.
  5. Hypermobile EDS – The diagnosis of hypermobile EDS (hEDS) is primarily clinical. As there is no molecular and genetic cause yet identified, there is no test available for almost all with hEDS.
  6. Arthrochalasia EDS – molecular testing detects the COL1A1 or COL1A2 genes.
  7. Dermatosparaxis EDS – molecular testing detects the ADAMTS2 gene.
  8. Kyphoscoliotic EDS (kEDS) – The majority of patients with kEDS harbor biallelic mutations in PLOD1; recently, biallelic mutations have been identified in FKBP14 in patients. Laboratory confirmation should start with a urine test using high-performance liquid chromatography (to evaluate the ratio of lysyl-pyridinoline to hydroxylysyl-pyridinoline crosslinks; a normal ratio is ~0.2, whereas kEDS-PLOD1 range is 2-9).
  9. Brittle cornea syndrome – molecular testing detects the ZNF469 or PRDM5 genes.
  10. Spondylodysplastic EDS – molecular testing detects the B4GALT7, B3GALT6, and SLC39A13 genes.
  11. Musculocontractural EDS – Musculocontractural EDS is caused by biallelic mutations in CHST14 detected by molecular testing
  12. Myopathic EDS (mEDS)- mEDS is caused by heterozygous or biallelic mutations in COL12A1 detected by molecular testing
  13. Periodontal EDS (pEDS) – pEDS is caused by heterozygous gain-of-function mutations in C1R or C1S detected by molecular testing
  • Physical testing using the Beighton Scale
  • The Beighton Scale is to assess how mobile your joints are, a search for abnormal scarring and testing your skin to determine what it feels like and how much it stretches.
  • Molecular testing results are useful to provide the basis for genetic counseling for our families also helpful in the guidance on treatment options.

What is the prognosis of Ehlers Danlos Syndrome?

  • Fortunately, there is treatment for symptoms of EDS.
  • There is no cure for the Ehlers Danlos syndrome, hence preventative measures are the life savers.
  • The prognosis usually depends on the type of Ehlers Danlos syndrome.
  • Those affected with the Vascular Ehlers Danlos syndrome will have lower Life expectancy as there are higher possibilities of rupture of visceral organs and blood vessels.
  • In the other subtypes, the life expectancy is usually not affected. The severity can be a mild or moderate range within a family.
  • Each affected individual of Ehlers Danlos syndrome will be unique.