Table 1 Characteristics of the study population: method of diagnosis shows either the mutation in COL3A1 if found, diagnosis by EDS specific electron microscopy of antebrachial skin biopsy or clinical phenotype evaluated by a geneticist. Major and minor symptoms include EDS and especially vascular type EDS specific symptoms based patients’ reports. Familial involvement shows positive family history (yes) in patients and A, B, C refer to distinct families, where more than one member participated in the study (Fig. 2). Medication shows daily and occasional drugs at the time of investigation. (y = years, f = female, m = male, SAB = subarachnoideal bleeding)

1

f

39

clinical

-

(uncomplicated delivery)

yes

Celiprolol

2

f

45

c3508G > A (p.G1170S)

hemorrhage

(mother/sister had lethal internal bleedings)

yes

-

3

f

44

Col3A1 c.1804C > A

hemorrhage, hypermenorrhea

(sister/niece have same vasc EDS mutation)

yes

Thyroxine, Venlafaxine

4

m

52

skin biopsy

cranial aneurysm, SAB

-

-

ASS, Metoprolol, Amiodarone

5

m

43

COL3A1:c.{973G > T};{=}

cranial aneurysm

-

A

-

6

m

13

COL3A1:c.{973G > T};{=}

-

hypermobility

A

-

7

f

22

c.2295_2312delTCCTATTGGTCCTCCTGG,p,lle767_Pro772del

vertebral aneurysm

hypermenorrhea

-

evtl Tranexamic acid

8

f

36

clinical

-

hypermobility

-

Thyroxine

9

m

53

clinical

-

multiple hernia

-

-

10

f

25

skin biopsy

internal bleeding

hypermobility,kissing spleen,varicose veins,valve insuffic

-

Tramadol,Bisoprolol,Duloxetine

11

f

75

COL3A1:IVS16 + 1G > A

cervical av-istula

hemorrhage, varicose veins, hypermobility

C

-

12

f

46

COL3A1:IVS16 + 1G > A

kidney infarction, SAB

hemorrhage, hematoma lower extremity, hypermobility

C

-

13

f

55

COL3A1:IVS16 + 1G > A

SAB

hypermobilita

C

-

14

f

29

COL3A1:IVS16 + 1G > A

-

spina bifida, hydrocephalus, hypermobility

C

-

15

f

41

clinical

atrial septum aneurysm

hemorrhage, hypermobility, mitral valve reflux

-

Nebivolol,Kodein,Prednisolon

16

f

50

skin biopsy, negative

Col5A/Col3A testing

hemorrhage

(six uncomplicated deliveries)

B

-

17

m

19

clinical

gastric perforation

hemorrhage

B

-

18

m

8

clinical

hemorrhage

impaired wound healing

B

-

19

m

9

clinical

-

facial stigmata of EDS

B

-

20

m

50

Col3A1 c.3544G > A

retroperitoneal hemotoma

-

-

-

21

f

25

Col3A1c.1258G > C

carotid dissection, stroke

contralateral asymptomatic dissection

-

-

22

f

49

skin biopsy

hemorrhage

gestational bleeding

-

-