Recurrence of occipital meningocele in 2 fetal sibs due to monoallelic MSX2 variant

Occipital encephaloceles are neural tube abnormalities characterized by a median defect of the occipital bone with herniation of brain structures usually contained in a membranous sac. Intracranial structures that protrude range from meninges (meningocele) to cerebral tissue such as occipital lobes, rarely cerebellum, brainstem or torcula. We present two fetal sibs with occipital meningocele caused by a maternal MSX2 variant identified by whole genome sequencing. Apart from the occipital meningocele, other cerebral abnormalities were found which led to the termination of the two pregnancies. The autopsy confirmed the prenatal findings. Upon clinical examination of the mother, a small scalp defect was discovered consistent with MSX2 gene variant. To our knowledge, only one case of occipital meningocele caused by MSX2 gene haploinsufficiency has been reported, with maternal inheritance. This paper is aimed at confirming the link between MSX2 gene variant and fetal occipital encephalocele, as well as its clinical variability.