Familial factor VII deficiency with foetal and neonatal fatal cerebral haemorrhage associated with homozygosis to Gly180Arg mutation.

ABSTRACT

Inherited factor VII (FVII) deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. Intracranial haemorrhage in infants has been previously reported in the severe form of the FVII deficiency and it has a high fatality rate. We report a family with high consanguineous relations, who experienced death of two baby girls, the first with prenatal manifestation of foetal hydrocephalus secondary to intracranial bleeding and the second with postnatal intracranial bleeding, both with less than 1% activity of FVII. Genetic analysis revealed that both parents are heterozygous and both daughters homozygous for a point mutation gG9639A in exon 7, predicting Gly180Arg substitution. This mutation was described previously in a compound heterozygous patient with mild bleeding manifestation. It seems that in this family, the mutation in its homozygous state is fatal and the lethal clinical expression can appear in utero at an early stage of gestation.