J Cerebrovasc Endovasc Neurosurg.  2020 Mar;22(1):15-19. 10.7461/jcen.2020.22.1.15.

Multiple cerebral cavernousmalformations in association witha Dubowitz-like syndrome

• Mostofi A
• Gurusinghe NT

• KMID: 2500069
• DOI: http://doi.org/10.7461/jcen.2020.22.1.15

Abstract

Cerebral cavernous malformations (CCMs) are proliferative sinusoidal vascular lesions and are the most common vascular malformations of the brain. They can occur sporadically or secondary to an underlying genetic predisposition where multiple lesions are commonly seen. Dubowitz syndrome is a clinically-diagnosed rare genetic disorder with an unknown molecular basis. An association between these conditions has not been reported previously. A 30-year-old woman with a Dubowitz- like syndrome presented with acute left leg weakness, gait ataxia and transient loss of consciousness. Imaging revealed five CCMs with recent hemorrhage in relation to one lesion in the left middle cerebellar peduncle. A recurrent hemorrhage from the same lesion occurred ten weeks later and she underwent microsurgical excision of this malformation. Genetic analysis revealed an unbalanced chromosomal rearrangement involving partial deletion of chromosome 7q21, the locus of the CCM1/ KRIT1 gene known to be associated with familial CCMs. This is the first description of CCMs in association with the Dubowitz phenotype. The genetic basis of Dubowitz syndrome may be heterogeneous but, for the first time, overlap is demonstrated between this condition and multiple CCMs, with a possible common genetic etiology. Knowledge of this association may be of help in the management of acute neurological presentations in Dubowitz-like syndromes.

Keyword

Hemangioma; Cavernous; Central nervous system; Dubowitz syndrome; Genetics

Figure

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  Fig. 1 brain MRI of the five cerebral cavernous malformations (CCMs) at initial presentation. Four of the lesions were apparent on T1-weighted (T1w) and T2-weighted (T2w) images: right frontal (A), right parietal (B), right temporal (C) and left middle cerebellar peduncle (D). All lesions are intraparenchymal (marked with arrows) and show the typical ‘pop corn’ appearance of CCMs with heterogeneous signal internally, surrounded by a T1w and T2w hypointense rim of haemosiderin. The right frontal and parietal lesions are shown on susceptibility weighted imaging (SWI) to demonstrate the characteristic blooming artefact (E, left image). The fifth, small left frontal lesion was apparent only as a focus of signal drop-out on SWI (E, right image). MRI, magnetic resonance imaging.

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  Fig. 2 brain magnetic resonance imaging following the second clinical presentation. There are new areas of T1w hyperintensity and T2w iso- to hypo-intensity at the site of the left middle cerebellar peduncle cerebral cavernous malformation suggestive of acute hemorrhage. There is an associated increase in mass effect on the surrounding brainstem and cerebellum when compared to the previous images (Fig. 1D).

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