Molecular Genetics of Hereditary Vascular Malformations


Vascular anomalies are divided into vascular tumours (mainly infantile haemangiomas) and vascular malformations. Vascular malformations are subdivided following the type of vessel affected: venous, capillary, arteriovenous and lymphatic. In addition to the pure forms, combined lesions are frequently encountered. Most of these malformations are sporadic, i.e. there is no family history, but familial cases, transmitted as an autosomal dominant or recessive trait, exist. During the last 10 years, the identification of diseaseā€causing genes implicated in the familial forms have resulted in a better classification of vascular anomalies, which has helped in assessment of treatment efficacy. These data have also unravelled the physiological role of the identified proteins during human vascular development.

Key concepts

  • Classification of vascular tumours and vascular malformations.

  • Vascular malformations are developmental anomalies.

  • Vascular malformations are classified depending on the affected vessels to capillary, venous, arterial, lymphatic or combined.

  • Sporadic and familial forms exist. Familial cases are often transmitted as an autosomal dominant disorder.

  • Several causative genes have been identified.

Keywords: genetics; vascular malformation; vein; capillary; lymphatic

Figure 1.

Vascular anomalies. (a) Voluminous hemangioma on the summit of the skull of a baby. (b) Hemifacial capillary malformation. (c) Characteristic capillary malformation of ‘CM‐AVM’: oval and light‐red appearance. Arrowheads indicate a pale halo around the malformation. (d) Arteriovenous malformation in an 8‐year‐old boy initially diagnosed as an infantile hemangioma. The lesion was warm and a thrill is felt on palpation. (e) Arteriography demonstrates abnormal vasculature. (f) Cerebral CT‐scan of a patient presenting cerebral cavernous malformation (arrowheads). (g) Characteristic glomuvenous malformations on the arm (arrow) and the leg (arrowhead) of a young boy. Note the nodular appearance and bluish‐purple colouration. (h) Venous malformations of the lips. Note their homogenous aspect and bluish colouration. (i) Subcutaneous lymphatic malformation on the axilla (arrows).



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Further Reading

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Brouillard P and Vikkula M (2003) Vascular malformations: localized defects in vascular morphogenesis. Clinical Genetics 63(5): 340–351.

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Aerts, Virginie, Boon, Laurence M, and Vikkula, Miikka(Mar 2009) Molecular Genetics of Hereditary Vascular Malformations. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021459]