WOREE is cause by homozygous nonsense mutation or compound heterozygous deletions and/or nonsense mutations in the WWOX gene.
SCAR12 is caused by homozygous missense mutations in the WWOX gene. Several
mutations have been documented and patients exhibit genotype-phenotype
correlations.
These rare recessive mutations of the WWOX gene causes a deficiency of this enzyme which has a severe impact on brain development. Further analyses will be required to fully understand the role of WWOX in these disorders.
Clinical clues for diagnosis:
Early-onset seizures (at 2 weeks to 3 months old), profound global developmental delay, hypomotor behaviour, several brain abnormalities, optic atrophy, and acquired microcephaly.
The EEG of WOREE patients shows a disorganized background either with focal or generalized epileptiform discharges.
Moreover, some consider that the lack of suppression-burst pattern on initial EEG as an important feature.
Cerebral imaging of WOREE patients reveals the presence of brain abnormalities as thin corpus callosum (even when imaging was performed early), followed by a supratentorial generalized volume loss, and a flat appearance of the mesencephalon later. Other electroclinical clues for diagnosis include persistent epileptic spasms and sleep-fragmented hypsarrhythmia associated with progressive cerebral atrophy without microcephaly.