El jueves y viernes 10 y 11 de mayo del 2018 realizamos en la Fundación Ramón Areces un Simposio Internacional, en el cual se trató el tema del mosaicismo somático en malformaciones vasculares.

1. Rudolf Happle
Department of Dermatology
University of Freiburg
Germany
A fresh look at capillary malformations:A fresh look at capillary malformations:
Why do we need particular namesWhy do we need particular names
for different vascular skin lesions?for different vascular skin lesions?
Madrid
10 May 2018

3. International Society for the Study of Vascular Anomalies
(ISSVA)

5. Capillary malformations
(CM)

6. According to the ISSVA,
the diagnosis is capillary malformation

7. According to the ISSVA,
the diagnosis is capillary malformation

8. Lee MS et al: J Am Acad Dermatol 2013
According to the ISSVA,
the diagnosis is capillary malformation

10. Klippel-Trenaunay syndrome: CM + VM +/− LM + limb overgrowth
Parkes-Weber syndrome: CM + AVF + limb overgrowth
Servelle-Martorell syndrome: limb VM + bone undergrowth
Sturge-Weber syndrome: facial + leptomeningeal CM + ocular anomalies +/
− bone and/or soft tissue overgrowth
Limb CM + congenital nonprogressive limb hypertrophy
Maffucci syndrome: VM +/− spindle cell hemangioma + enchondroma
Macrocephaly-CM (M-CM)/megalencephaly-CM-polymicrogyria (MCAP)
Microcephaly-CM (MICCAP)
CLOVES syndrome: LM + VM + CM +/− AVM + lipomatous overgrowth
Proteus syndrome: CM, VM and/or LM + asymmetric somatic overgrowth
Bannayan-Riley-Ruvalcaba syndrome: AVM + VM + macrocephaly,
lipomatous overgrowth
Wassef M et al and ISSVA Board and Scientific Committee: Pediatrics 2015
Vascular Anomalies Classification:
Recommendations From the International Society for the Study of Vascular Anomalies
For clinical dermatologists
this classification is worthless!

12. Capillary nevi

13. All of these capillary neviAll of these capillary nevi
can occurcan occur
without any extracutaneous anomaly!without any extracutaneous anomaly!

14. Rhodoid nevus (Vikkula nevus)Rhodoid nevus (Vikkula nevus)
Nevus vascularis mixtusNevus vascularis mixtus
Congenital livedo reticularisCongenital livedo reticularis
Nevus flammeusNevus flammeus
Nevus roseusNevus roseus
GNAQ
GNA11
RASA1
EPHB4
PIK3CA
?
?

16. Nevus roseus
versus
nevus flammeus

18. Diociaiuti A et al:
J Am Acad Dermatol 2005
Jordaan HF, Happle R:
Br J Dermatol 2008
Phacomatosis spilorosea:
Macular nevus spilus combined with nevus roseus
Happle R:
J Eur Acad Dermatol Venereol
2015

21. A rather frequently occurring capillary malformation
that deserves a specific name:
Rhodoid nevus
(Vikkula nevus)
Thanks to
Dr. Regina Fölster-Holst, Kiel, Germany

22. Miikka VikkulaMiikka Vikkula
Professor of Human GeneticsProfessor of Human Genetics
BrusselsBrussels
2003:2003:
A new autosomal dominant phenotypeA new autosomal dominant phenotype
„„capillary malformation-arteriovenous malformation“capillary malformation-arteriovenous malformation“
(CM-AVM), being caused by(CM-AVM), being caused by RASA1RASA1 mutationsmutations

23. 2003:2003:
A new autosomal dominant phenotypeA new autosomal dominant phenotype
„„capillary malformation-arteriovenous malformation“capillary malformation-arteriovenous malformation“
(CM-AVM), being caused by(CM-AVM), being caused by RASA1RASA1 mutationsmutations

24. Revencu N and 51 coauthors:
Hum Mutation 2013
Type 2 segmental manifestation
= bias of ascertainment

25. Revencu N et al: Hum Mutation 2008Revencu N et al: Hum Mutation 2008
„„Capillary malformation-arteriovenous malformation“:Capillary malformation-arteriovenous malformation“:
The arteriovenous malformation is aThe arteriovenous malformation is a
type 2 segmental manifestation of the syndrome!type 2 segmental manifestation of the syndrome!

26. rhodoidesrhodoides = rose-colored= rose-colored
Courtesy ofCourtesy of
Dr. Cornelia Seitz,Dr. Cornelia Seitz,
Göttingen,GermanyGöttingen,Germany
Rhodoid nevusRhodoid nevus
(Vikkula nevus)

27. Courtesy ofCourtesy of
Dr. Cornelia Seitz,Dr. Cornelia Seitz,
Göttingen,GermanyGöttingen,Germany
Why a new name?

28. „„Nomina si nescis, perit et cognitio rerum.“Nomina si nescis, perit et cognitio rerum.“
Carl von LinnéCarl von Linné
1707-17781707-1778
Si no se conocen los nombres, losSi no se conocen los nombres, los
conocimientos de estas cosas se pierden.conocimientos de estas cosas se pierden.

29. Thanks to
Dr. Antonio Torrelo, Madrid
The pale halo
is very
characteristic,
but…

30. Chee D et al: J Pediatr Surg 2010
…it is
not always
present!

32. Amyere M et al: Circulation 2017

34. Conclusion:Conclusion:
Rhodoid nevi (Vikkula nevi) occur rather frequently.Rhodoid nevi (Vikkula nevi) occur rather frequently.
They are inherited as an autosomal dominant trait.They are inherited as an autosomal dominant trait.
An arteriovenous malformation („CM-AVM“)An arteriovenous malformation („CM-AVM“)
isis notnot an obligatory criterion.an obligatory criterion.
They reflect a mutation inThey reflect a mutation in RASA1 or EPHB4RASA1 or EPHB4..

36. Torrelo A et al:
J Eur Acad Dermatol Venereol 2006
Del Boz González J et al:
An Pediatr (Barc) 2008
Cutis marmorata telangiectatica congenita

38. …is a hallmark of
congenital livedo reticularis-megalencephaly syndrome
(„macrocephaly-capillary malformation syndrome“)
Congenital livedo reticularis

39. Cutis marmorataCutis marmorata
telangiectatica congenitatelangiectatica congenita
CongenitalCongenital
livedo reticularislivedo reticularis
The cause is so far
unknown
PIK3CA
Rivière JB et al:
Nat Genet 2012

40. Congenital livedo reticularis-megalencephaly
syndrome
MegalencephalyMegalencephaly PolymicrogyriaPolymicrogyria Ventriculomegaly
Mirzaa GM et al: Am J Med Genet 2012Mirzaa GM et al: Am J Med Genet 2012
[„Megalencephly-capillary malformation (M-CAP)“]

41. Swarr DT et al:Swarr DT et al:
Prenatal Diagnosis 2013Prenatal Diagnosis 2013
Congenital livedo reticularis
Gonzalez ME et al:
Pediatr Dermatol 2009

42. Lee MS et al: J Am Acad Dermatol 2013
Congenital
livedo reticularis

44. Plötz SG et al:
Br J Dermatol 1998
Thanks to Dr. Sigrid Tinschert,
Berlin, Germany
Chen WC et al: Dermatology 2006
Thanks to Dr. Henning Hamm,
Würzburg, Germany
Port-wine nevus
of the Proteus type
Port-wine nevus
of the CLOVES type
Angiokeratoma
circumscriptum
Segmental angioma
serpiginosum
Nevus anemicus Nevus vascularis mixtus
Thanks to Dr. Helena de las Heras,
Madrid, Spain
Other capillary nevi

46. Capillary nevi in limbo
(capillary malformations that
probably represent nevi)

47. Midfacial port-wine patch

48. Midfacial port-wine patch

49. Macrocephaly–Capillary Malformation: Analysis of 13 Patients and Review of the
Diagnostic Criteria
Víctor Martínez-Glez, Valeria Romanelli, María A. Mori, Ricardo Gracia, Mabel Segovia,
Antonio Gonzalez-Meneses, Juan C. Lopez-Gutierrez, Esther Gean, Loreto Martorell, Pablo Lapunzina
Am J Med Genet Part A 2010
Midfacial port-wine patch

51. Krämer D et al: Int J Dermatol 2016
Midfacial port-wine patch of the CLAPO type

52. Am J Med Genet Part A 2008
PIK3CA
Rodriguez-Laguna L et al: Genet Med 2018

53. Krämer D et al: Int J Dermatol 2016
Midfacial port-wine patch of the CLAPO type

54. Genet Med 2018

56. Isidor B et al: Am J Med Genet 2011
Carter-Mirzaa macules
„„MICCAP“MICCAP“
STAMPBSTAMPB mutationsmutations
Grimaldi M et al: Acta Derm Venereol 2006
Unilateral punctate telangiectasia
Unilateral nevoid telangiectasia of the patchy type
Other capillary nevi in limbo

58. Capillary non-nevi

59. Juern AM et al: J Am Acad Dermatol 2010
Salmon patch

60. Autosomal dominant
angiokeratoma
corporis diffusum
5 capillary non-nevi
Salmon patch
Osler disease
Fabry disease
Calzavara-Pinton PG et al: Arch Dermatol 1995
Hereditary angioma serpiginosum
Marriott PT et al: Br J Dermatol 1975

62. • Nevus flammeus
• Port-wine nevus of the Proteus type
• Port-wine nevus of the CLOVES type
• Nevus roseus
• Rhodoid nevus (Vikkula nevus)
• Cutis marmorata telangiectatica
congenita
• Congenital livedo reticularis
• Segmental angioma serpiginosum
• Nevus anemicus
• Nevus vascularis mixtus
• Angiokeratoma circumscriptum
• Midfacial port-wine patch
• Midfacial port-wine patch of the CLAPO type
• Carter-Mirzaa macule
• Unilateral punctate telangiectasia
• Unilateral nevoid telangiectasia of the patchy
type
• Salmon patch
• Hereditary hemorrhagic telangiectasia
• Fabry disease
• Autosomal dominant angiokeratoma
corporis diffusum
• Hereditary angioma serpiginosum
Capillary neviCapillary nevi Capillary neviCapillary nevi in limboin limbo
Capillary non-neviCapillary non-nevi
21 different capillary malformations

64. Different capillary malformations:Different capillary malformations:
Rhodoid nevusRhodoid nevus
Nevus vascularis mixtusNevus vascularis mixtus
Livedo reticularisLivedo reticularis
congenitacongenita
Segmental angiomaSegmental angioma
serpiginosumserpiginosum
Nevus roseusNevus roseusNevus flammeusNevus flammeus
Nevus anemicusNevus anemicus
AngiokeratomaAngiokeratoma
circumscriptumcircumscriptum
Cutis marmorataCutis marmorata
telangiectatica congenitatelangiectatica congenita
„Capillary malformation“
is an
asylum ignorantiae
Salmon patchSalmon patch Fabry diseaseFabry disease Rendu-Osler diseaseRendu-Osler disease
Happle R: J Eur Acad Dermatol Venereol 2015

66. Thank you!

71. Nevus vascularis mixtus

73. Ruggieri M et al: Am J Med Genet 2012Ruggieri M et al: Am J Med Genet 2012
Nevus vascularis mixtus syndromeNevus vascularis mixtus syndrome

74. Nevus vascularis mixtus syndromeNevus vascularis mixtus syndrome
Intracerebral vascular malformations
Ruggieri M et al: Am J Med Genet 2012Ruggieri M et al: Am J Med Genet 2012