Abstract
Familial cerebral cavernous malformation syndromes are most commonly caused by mutations
in one of three genes. The overlap of these genetic malformations with other acquired
neoplastic lesions and congenital malformations is still under investigation. To the
best of our knowledge, the concurrent occurrence of familial cavernous malformations
and ependymoma has not been previously reported in the literature. Herein, we describe
a patient with familial cerebral cavernous malformation syndrome and posterior fossa
ependymoma. A 17-year-old asymptomatic male was referred to our outpatient neurosurgery
clinic after genetic testing identified a familial KRIT1 (CCM1) mutation. The patient's
sister had presented with a seizure disorder previously; multiple cavernous malformations
were discovered, and a symptomatic large cavernous malformation required a craniotomy
for resection. Two years later, she was diagnosed with follicular thyroid cancer due
to HRAS (c.182A>G) mutation. The patient and his sister were found to have a novel
germline KRIT1 disease-causing variant (c.1739deletion, p.ASN580Ilefs*2) and a variant
of uncertain significance, potentially pathogenic (c.1988 A>G, p.Asn663Ser) in cis
in CCM1 (KRIT1), of paternal inheritance. Due to the presence of genetic abnormalities,
the patient underwent screening imaging of his neuraxis. Multiple cavernous malformations
were identified, as was an incidental fourth ventricular mass. Resection of the fourth
ventricular lesion was performed, and histopathological examination was consistent
with ependymoma. We report a unique case of posterior fossa ependymoma in an individual
with a familial cerebral cavernous malformation syndrome and a novel genetic abnormality
in KRIT1. The association of these two findings may be valuable in determining a potential
genetic association between the two pathologies and elucidating the pathogenesis of
both cavernous malformations and ependymomas.
Keywords
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Article Info
Publication History
Published online: May 03, 2020
Accepted:
April 15,
2020
Received in revised form:
March 2,
2020
Received:
October 29,
2019
Identification
Copyright
© 2020 Elsevier Inc. All rights reserved.
