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Ehlers-Danlos syndrome type 4

MIM.130050 2q31

Monday 24 January 2005

Ehlers-Danlos syndrome type IV is the vascular type of Ehlers-Danlos syndromes (EDSs).

It is an autosomal dominant collagen disease defined by characteristic facial features (acrogeria) in most patients, translucent skin with highly visible subcutaneous vessels on the trunk and lower back, easy bruising, and severe arterial, digestive and uterine complications, which are rarely, if at all, observed in the other forms of EDS.

The estimated prevalence for all EDS varies between 1/10,000 and 1/25,000, EDS type IV representing approximately 5 to 10% of cases.

The vascular complications may affect all anatomical areas, with a tendency toward arteries of large and medium diameter.

Dissections of the vertebral arteries and the carotids in their extra- and intra-cranial segments (carotid-cavernous fistulae) are typical. There is a high risk of recurrent colonic perforations. Pregnancy increases the likelihood of a uterine or vascular rupture.

EDS type IV is inherited as an autosomal dominant trait that is caused by mutations in the COL3A1 gene coding for type III procollagen.

Diagnosis is based on clinical signs, non-invasive imaging, and the identification of a mutation of the COL3A1 gene.

Clinical differential diagnosis

- In childhood

- In adulthood

Synopsis

- short stature
- pinched nose
- thin nose
- thin lips
- lobeless ears
- keratoconus
- periodontal disease
- early loss of teeth
- mitral valve prolapse
- spontaneous pneumothorax
- hemoptysis
- inguinal hernia
- spontaneous rupture of bowel
- uterine rupture associated with pregnancy
- uterine prolapse
- bladder prolapse
- hypermobility of distal interphalangeal joints
- acroosteolysis
- club foot
- acroosteolysis
- fragile skin
- easy bruisability
- cigarette-paper scars
- atrophic skin over ears
- prominent venous markings
- absent-mild skin hyperextensibility
- skin changes worse in areas of lower skin temperature
- molluscoid pseudotumors
- acrogeria (skin over hands and feet are thin and finely wrinkled)
- alopecia of scalp
- premature delivery because of cervical insufficiency or membrane fragility
- death usually occurs before 5th decade

- arterial anomalies

  • coronary arteriomegaly
  • arterial aneurysms
    • intracranial aneurysms
  • spontaneous arterial rupture
  • bilateral renal artery dissection
  • hematoma of the ascending aorta

- spontaneous hepatic rupture (10852630, 9286240)

Associations

- hepatic epithelioid hemangioendothelioma
- situs solitus with dextrocardia

Etiology

- germline mutations in the gene COL3A1 coding for type III collagen (COL3s) (MIM.120180)

See also

- connective tissue diseases

References

- Germain DP. Ehlers-Danlos syndrome type IV. Orphanet J Rare Dis. 2007 Jul 19;2(1):32 PMID: 17640391