ALX4 related parietal foramina mimicking encephalocele in prenatal period

Abstract

What's Already Known About This Topic? PFM is an autosomal dominantly inherited genetic condition, caused by mutations in ALX4 and MSX2 genes. Reports on prenatally diagnosed cases are rare, and encephalocele remains the most leading differential diagnosis. What Does This Study Add? The full clinical spectrum of autosomal dominant ALX4‐related PFM in affected family members can be demonstrated through identification of a prenatal case, by close collaboration of perinatologists and clinical geneticists, as in the four generation family reported herein.

Identification of a novel homozygous ALX4 mutation in two unrelated patients with frontonasal dysplasia type‐2

“…Despite these malformations of the occipital lobes, our patients and those described in the literature are free of neurological abnormalities. Furthermore, bilateral cystic masses (simulating the meningocele) over the PEM with intact meningeal membranes were observed either with heterozygous (c.730C > T and c.418C > T) or homozygous (c.207delG) ALX4 mutations (Mavrogiannis et al, ; Meloni et al, ; Saraç Sivrikoz et al, ). These meningocele‐like cysts were similarly observed in Patient 1 that increased in size with age.…”

“…This was evidenced by the presence of mild phenotype reported with homozygous missense mutation (Kariminejad et al, ) when compared with those with homozygous ALX4 truncating mutations (nonsense and frameshift) (Alanay et al, ; Kariminejad et al, ; Kayserili et al, ; Meloni et al, ). Furthermore, heterozygous mutations of ALX4 gene were assumed to yield a PFM that is segregated in an autosomal dominant mode of inheritance with full penetrance (Bertola et al, ; Mavrogiannis et al, ; Saraç Sivrikoz et al, ; Valente et al, ). This raises the intriguing possibility that mutations with less dramatic effect on the protein function may result in a less severe phenotype.…”

“…This raises the intriguing possibility that mutations with less dramatic effect on the protein function may result in a less severe phenotype. Interestingly, besides the PFM described in families with heterozygous allele, malformations of vascular and cortical development, meningocele‐like cysts, and mild frontonasal phenotype combining cryptorchidism were described in few families (Bertola et al, ; Saraç Sivrikoz et al, ; Valente et al, ). The vertical transmission of these anomalies showed intrafamilial variability.…”

Prenatal diagnosis of familial atretic encephalocele

“…The subscalp bulges, which contain the meninges or remnants of glial or neural tissues, have been termed atretic encephalocele. Therefore, identification of similarly affected family members by clinical examination, with or without radiological evaluation, as well as close collaboration with perinatologists and clinical geneticists, is of paramount importance in the management of both enlarged parietal foramina and occipital encephalocele.…”