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CORRESPONDENCE
Year : 2022  |  Volume : 67  |  Issue : 3  |  Page : 295-296
Capillary malformation-arteriovenous malformation syndrome due to EPHB4 gene mutation: Clinical, dermoscopic, ecographic and histopathological features


1 Department of Dermatology, Hospital Universitari Sagrat Cor-Grupo Hospitalario QuirónSalud, Barcelona, Spain
2 Department of Pathology, Hospital Universitari General de Catalunya-Grupo Hospitalario QuirónSalud, Barcelona, Spain

Date of Web Publication22-Sep-2022

Correspondence Address:
Nuria Setó-Torrent
Department of Dermatology, Hospital Universitari Sagrat Cor-Grupo Hospitalario QuirónSalud, Barcelona
Spain
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_769_20

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How to cite this article:
Setó-Torrent N, Iglesias-Sancho M, Altemir-Vidal A, Quintana-Codina M, Fernández-Figueras MT, Salleras-Redonnet M. Capillary malformation-arteriovenous malformation syndrome due to EPHB4 gene mutation: Clinical, dermoscopic, ecographic and histopathological features. Indian J Dermatol 2022;67:295-6

How to cite this URL:
Setó-Torrent N, Iglesias-Sancho M, Altemir-Vidal A, Quintana-Codina M, Fernández-Figueras MT, Salleras-Redonnet M. Capillary malformation-arteriovenous malformation syndrome due to EPHB4 gene mutation: Clinical, dermoscopic, ecographic and histopathological features. Indian J Dermatol [serial online] 2022 [cited 2022 Sep 30];67:295-6. Available from: https://www.e-ijd.org/text.asp?2022/67/3/295/356755




Sir,

A 19-year-old otherwise healthy man presented with seven erythematous brownish macules with geographic borders, from 1 to 1.5 cm, located on the face, trunk and both arms [Figure 1]a, [Figure 1]b. The lesions were present at early birth and had progressively increased in number. None of them were warm or pulsatile. He also had two telangiectasia on the lower lip. Polarized dermoscopy showed a vascular pattern with branched vessels on a light brown background [Figure 2]a. On pressure, the vascular pattern disappeared revealing a light brown network with hair follicle openings [Figure 2]b. Doppler ultrasonography revealed no increased blood flow and histopathology showed a mild increase in the number of vessels throughout the dermis showing small diameter, dilated lumens and a thin myopericitic coat [Figure 3]. Genetic testing demonstrated an heterozygous stop mutation in EPHB4 gene (c. 2215 C > T; p.Arg739), and diagnosis of capillary malformation-arteriovenous malformation (CM-MAV) syndrome was confirmed. Cerebral and spinal magnetic resonance imaging were normal. His father and brother had similar lesions over the body; however, they did not undergo genetic testing.
Figure 1: a. Erythematous brownish macules with geographic borders on the trunk. b. Erythematous macule on the chin and two telangiectasia on the lower lip

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Figure 2: (a) Dermoscopy without pressure: vascular pattern with branched vessels on a light brown background (DermLite DL200Hybrid, ×10). (b) Dermoscopy on pressure: disappearance of the vascular pattern revealing a light brown network with hair follicle openings (DermLite DL200Hybrid, ×10)

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Figure 3: Mild proliferation and dilatation of vessels of small diameter throughout the dermis (Hematoxilin-Eosin staining, 10x)

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CM-MAV syndrome is an autosomal dominant disorder associated with heterozygous inactivating mutations in RASA1 or EPHB4 genes. It is characterized by multifocal cutaneous capillary malformations (CMs), sometimes associated with either arteriovenous malformations (AVMs) or fistulas (AVFs).[1]

The CMs appear as congenital or acquired, reddish-brown macules that may be surrounded by a whitish peripheral halo suggesting an associated steal phenomenon and have an increase in local temperature.[1] Dermoscopy shows a mixed vascular and pigmentary pattern with branched linear vessels associated with an underlying brown background. The vascular pattern disappears on compression revealing a pigmentary reticular pattern.[2] Reported sonographic findings include increased blood flow, dilated blood vessels and fast flows in mid-lower dermis and subcutaneous tissue suggesting that these lesions could be the expression of an early or small underlying AVM.[3] Histopathology reveals a proliferation and dilatation of superficial and/or deep capillaries and venules in dermis, and despite it could be useful, it is not required in typical cases.[3] Up to a third of patients can associate AVMs/AVFs typically found in soft tissue, bone, brain, or spinal cord, and can cause life-threatening complications.[1]

Amyere et al.[4] suggested that disorders caused by RASA1 and EPHB4 be referred to as CM-AVM1 and CM-AVM2, respectively. The CM-AVM2 phenotype is characterized by a lower risk of AVMs/AVFs and the possible presence of Bier spots, telangiectasias and recurrent epistaxis.[4] According to these features, our patient presented telangiectasias in the lower lip and did not associate fast-flow vascular anomalies. Imaging of the brain and spine should be performed at diagnosis and repeated if new symptoms develop.[5] Genetic testing for RASA1 and EPHB4 mutations of both patient and parents and genetic counselling is recommended.[4],[5]

CM-AVM is an underrecognized disorder in which patients need to be screened for RASA1 as well as EPHB4 mutations and the existence of fast-flow vascular anomalies should be ruled out. Although CM-AVM2 has a lower risk of AVMs/AVFs, follow-up is needed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Revencu N, Boon LM, Mendola A, Cordisco MR, Dubois J, Clapuyt P, et al. RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation. Hum Mutat 2013;34:1632-41.  Back to cited text no. 1
    
2.
Gandon C, Bonniaud B, Collet E, Dalac S, Jeudy G, Vabres P. A typical vascular and pigmentary dermoscopic pattern of capillary malformations in capillary malformation-arteriovenous malformation syndrome: Report of four cases. Pediatr Dermatol 2016;33:e337-41.  Back to cited text no. 2
    
3.
Kim C, Ko CJ, Baker KE, Antaya RJ. Histopathologic and ultrasound characteristics of cutaneous capillary malformations in a patient with capillary malformation-arteriovenous malformation syndrome. Pediatr Dermatol 2015;32:128-31.  Back to cited text no. 3
    
4.
Amyere M, Revencu N, Helaers R, Pairet E, Baselga E, Cordisco M, et al. Germline loss-of-function mutations in EPHB4 cause a second form of capillary malformation-arteriovenous malformation (CM-AVM2) deregulating RAS-MAPK signaling. Circulation 2017;136:1037-48.  Back to cited text no. 4
    
5.
Orme CM, Boyden LM, Choate KA, Antaya RJ, King BA. Capillary malformation--arteriovenous malformation syndrome: Review of the literature, proposed diagnostic criteria, and recommendations for management. Pediatr Dermatol 2013;30:409-15.  Back to cited text no. 5
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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