BACKGROUND: Cerebral cavernous malformations (CCM) present as either sporadic or 
autosomal dominant conditions with incomplete penetrance of symptoms. 
Differences in genetic and environmental factors might be minimized among 
first-degree relatives. We therefore studied clinical expression in a family 
with several affected members.
METHODS: We studied a three-generation family with the onset of CCM as a 
cerebral haemorrhage in the younger (four-year-old) sibling. Identification and 
enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the 
whole brains. Genetic analysis comprised SCCP, sequencing and restriction 
polymorphism of the Krit1 gene in the proband and at risk relatives.
RESULTS: The phenotypes of cerebral cavernous malformations (CCMs) in carriers 
of Krit1 mutations were very variable. We identified a novel frameshift mutation 
caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a 
premature TAA triplet and predicts the truncating phenotype Y634X. A very 
striking finding was the absence of both clinical symptoms and CCMs in the 
eldest sibling harbouring the 1902insA.
CONCLUSIONS: Patients in this family, harbouring the same mutation, illustrate 
the very variable clinical and radiological expression of a Krit1 mutation. The 
early and critical onset in the proband contrasts with minor clinical findings 
in affected relatives. This consideration is important in genetic counselling.