NID1 variant associated with occipital cephaloceles in a family expressing a spectrum of phenotypes.

Autosomal dominant Dandy-Walker malformation and occipital cephalocele (ADDWOC) is a rare, congenital, and incompletely penetrant malformation that is considered to be part of the Dandy-Walker spectrum of disorders. Affected individuals often present with an occipital cephalocele with a bony skull defect, but typically have normal neurological development. Here, we report on a three-generation family in which individuals have variable phenotypes that are consistent with the ADDWOC spectrum: arachnoid cysts in the proband and his maternal grandfather, an occipital cephalocele in the proband and his brother, and a small bony defect in the proband's mother. Whole exome sequencing identified a rare heterozygous variant in NID1 (NM_002508.2:c.1162C>T, (p.Gln388Ter)) in the proband, his brother, and his mother. Sanger sequencing confirmed the presence of this variant in the maternal grandfather. The identical c.1162C>T variant was previously identified in variably affected members of a three-generation family with ADDWOC. This case report provides further evidence that variants in NID1 may be clinically relevant for the development of a phenotype that is consistent with ADDWOC, and extends the phenotype of NID1-associated ADDWOC to include arachnoid cysts. Given that the Dandy-Walker malformation itself is not a pre-requisite to this spectrum of phenotypes, we also suggest a novel term for the NID1-associated disorder in order to give emphasis to this phenotypic variability: "Autosomal Dominant Posterior Fossa Anomalies with Occipital Cephaloceles."

Dilated intracranial translucency and Blake's pouch cyst: first-trimester ultrasound markers of occipital cephalocele diagnosed using novel three-dimensional reslicing technique.

Abnormal intracranial translucency (IT) (fourth ventricle) and a Blake's pouch cyst with normal brain stem cavity may be valuable first-trimester call signs of defects in the skull base. Here, we report a case of presumptive two-dimensional sonographic diagnosis of occipital cephalocele that was posed at the time of 11-13 weeks aneuploidy scan. The two-dimensional sonographic finding elicited a detailed fetal neuroscan that was performed using either multiplanar mode or a novel three-dimensional reslicing and lightening technique. The use of three-dimensional sonographic software and offline "navigation" within the volume of interest enabled operators to capture a diagnostic snapshot of the condition, enhancing quality imaging and early detection of the encephalic lesion.