<%server.execute "isdev.asp"%> Multiple cerebral cavernous haemangiomas in an infant Verma P, Saleem R, Harijan P, Hussain N - J Pediatr Neurosci
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CASE REPORT
Year : 2012  |  Volume : 7  |  Issue : 3  |  Page : 200-201
 

Multiple cerebral cavernous haemangiomas in an infant


Department of Paediatric Neurology, Leicester Royal Infirmary, Leicester, LE1 5WW, United Kingdom

Date of Web Publication25-Jan-2013

Correspondence Address:
Pooja Harijan
Department of Paediatric Neurology, Leicester Royal Infirmary, LE1 5WW
United Kingdom
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1817-1745.106479

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   Abstract 

Cerebral cavernous malformations (CCMs) are vascular malformations causing seizures and cerebral hemorrhages. We report a 20-month old male with multiple CCMs associated with Krev interaction trapped 1 (KRIT1) c.845 + 1 G > C heterozygous transversion mutation. This case demonstrates the importance of molecular genetic analysis in cases of multiple CCM.


Keywords: Angioma, cavernoma, cavernous haemangioma, seizure


How to cite this article:
Verma P, Saleem R, Harijan P, Hussain N. Multiple cerebral cavernous haemangiomas in an infant. J Pediatr Neurosci 2012;7:200-1

How to cite this URL:
Verma P, Saleem R, Harijan P, Hussain N. Multiple cerebral cavernous haemangiomas in an infant. J Pediatr Neurosci [serial online] 2012 [cited 2019 Dec 6];7:200-1. Available from: http://www.pediatricneurosciences.com/text.asp?2012/7/3/200/106479



   Introduction Top


Cerebral cavernous malformations (CCMs) are usually located in the white matter of the brain. Most malformations are supratentorial, the frontal and temporal lobes being the most common sites of occurrence. Grossly, they appear as small mulberries. Histoarchitecture consists of a single layer of endothelium with differing quantities of subendothelial fibrous stroma with distinct absence of smooth muscle and elastic fibres. Nearly all cavernous malformations show evidence of recent and remote hemorrhage, as suggested by the presence of hemosiderin-laden macrophages, cholesterol crystals and hemosiderin-stained parenchymal tissues. Patients with cavernous angiomas may remain asymptomatic, but clinically evident hemorrhage is the most worrisome consequence. The highest incidence of hemorrhage occurs in the second or third decade of life. Seizures were the most common presentation in the majority of cases in two case series. [1],[2]


   Case Report Top


A 20-month-old male infant presented with two episodes of focal seizures, each lasting 4 minutes and consisting of staring, lip and teeth clenching, and eye deviation to one side followed by stiffening and jerking of all four limbs. He had an antenatal ultrasound finding of an intracranial cyst. The pregnancy was otherwise uneventful and delivery and early development were normal. He had a past history of two febrile convulsions associated with upper respiratory tract infections. Electroencephalography showed normal background rhythms visible at times but the recording was dominated by runs of high-amplitude rhythmic sharpened slow waves most prominent in the right lateral leads and bi-frontally. Magnetic resonance imaging (MRI) [Figure 1] showed a right frontal cavernous haemangioma with typical, popcorn-like, smoothly circumscribed, well- delineated complex lesion features. The core is formed by multiple foci of mixed signal intensities representing haemorrhage in various stages of evolution. His seizures were refractory to initial management with carbamazepine and the angioma was resected. He continued to have seizures following resection. Repeat MRI brain at age 4 years showed a new cavernous angioma [Figure 2]. Genetic analysis showed a c.845 + 1 G > C heterozygous transversion mutation of the Krev interaction trapped 1 (KRIT 1) gene.
Figure 1: Right frontal cavernous hemangioma

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Figure 2: New right frontal cavernous hemangioma

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   Discussion Top


Multiple CCMs are associated with autosomal dominant genetic mutations. [3] Three genetic loci have been found: CCM1 and CCM2 on chromosome 7 and CCM3 on chromosome 3. [3] The KRIT1 gene is a gene located within the CCM1 locus on chromosome 7 encoding the KRIT-1 protein. Mutations identified to date mostly cause a premature stop codon resulting in a lack of KRIT-1 protein. Some evidence has been found for a role for KRIT-1 in the early development of blood vessels. CCM1 knockout mouse models [4] have demonstrated that CCM1 is expressed early in embryogenesis and is essential for vascular development. KRIT-1 has been found to be expressed in endothelial cells [5] and in particular during early angiogenesis. [6] In a case series of patients [7] with multiple CCMs, 28% were found to have a mutation within the CCM1 locus. In a second case series [3] of cases with multiple CCMs or an affected relative, 43% were found to have a mutation within the CCM1 locus.


   Conclusions Top


As genetic mutations associated with cerebral cavernous angiomas are identified and their prognostic implications understood, it is important that genetic testing is considered in patients with cavernous angiomas and in particular in those with multiple cavernous angiomas. [8]

 
   References Top

1.Garcia-Morales I, Gomez-Escalonilla C, Galan L, Rodriguez R, Simon De Las Heras R, et al. Cerebral cavernomas in childhood. clinical presentation and diagnosis. Rev Neurol 2002;34:339-42.  Back to cited text no. 1
    
2.Di Rocco C, Iannelli A, Tamburrini G. Cavernomas of the central nervous system in children. A report of 22 cases. Acta Neurochir (Wien) 1996;138:1267-74.  Back to cited text no. 2
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3.Cavé-Riant F, Denier C, Labauge P, Cécillon M, Maciazek J, Joutel A, et al. Spectrum and expression analysis of KRIT1 mutations in 121 consecutive and unrelated patients with cerebral cavernous malformations. Eur J Hum Genet 2002;10:733-40.  Back to cited text no. 3
    
4.Whitehead KJ, Plummer NW, Adams JA, Marchuk DA, Li DY. CCM1 is required for arterial morphogenesis: Implications for the etiology of human cavernous malformations. Development 2004;131:1437-48.  Back to cited text no. 4
    
5.Gunel M, Laurans MS, Shin D, DiLuna ML, Voorhees J, Choate K, et al. KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proc Natl Acad Sci U S A 2002;99:10677-82.  Back to cited text no. 5
    
6.Guzeloglu-Kayisli O, Kayisli UA, Amankulor NM, Voorhees JR, Gokce O, DiLuna ML, et al. Krev1 interaction trapped-1/cerebral cavernous malformation-1 protein expression during early angiogenesis. J Neurosurg 2004;100:481-7.  Back to cited text no. 6
    
7.Verlaan DJ, Laurent SB, Sure U, Bertalanffy H, Andermann E, Andermann F, et al. CCM1 mutation screen of sporadic cases with cerebral cavernous malformations. Neurology 2004;62:1213-5.  Back to cited text no. 7
    
8.Laberge-le Couteulx S, Jung HH, Labauge P, Houtteville JP, Lescoat C, Cecillon M, et al. Truncating mutations in CCM1, encoding KRIT1, cause hereditary cavernous angiomas. Nat Genet 1999;23:189-93.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2]


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