Martinez-Lage et al. (1996) reported 3 sibs with occipital atretic cephaloceles, skin-covered subscalp lesions containing meninges or remnants of glial or neural tissues. Neuroimaging studies showed a spectrum of posterior fossa cystic malformations.
Bassuk et al. ... Martinez-Lage et al. (1996) reported 3 sibs with occipital atretic cephaloceles, skin-covered subscalp lesions containing meninges or remnants of glial or neural tissues. Neuroimaging studies showed a spectrum of posterior fossa cystic malformations. Bassuk et al. (2004) reported a Vietnamese American kindred in which 7 members spanning 3 generations had occipital atretic cephalocele inherited in an autosomal dominant pattern. The proband was diagnosed with hydrocephalus in utero, had macrocephaly at birth, and showed progressive hydrocephalus necessitating a shunt at 4 months of age. At birth, he had a 1.5 cm by 1.5 cm skin-covered occipital lesion. There were no dysmorphic features. Brain MRI showed a skull defect with cephalocele, partial callosal agenesis, a large ventricular diverticulum extending into the interhemispheric fissure, and subependymal heterotopia. At age 15 months, the patient had significant motor delay and poor vocabulary. Other affected family members, including the patient's mother, had occipital subscalp nodules ranging from approximately 2 to 4 cm and normal neurologic examinations. Several obligate carriers had no nodules, indicating incomplete penetrance. Bassuk et al. (2004) noted that only the proband in this family had additional neurologic manifestations. Jalali et al. (2008) provided follow-up of the Vietnamese family reported by Bassuk et al. (2004). Upon further imaging, the authors recategorized the family as having autosomal dominant Dandy-Walker malformation with occipital cephalocele (see 220200). Seven individuals without obvious cephalocele showed posterior fossa and cerebellar changes on MRI that were consistent with the diagnosis. Only the 2 individuals in the third generation, including the proband from the previous report, had neurologic manifestations. Carvalho et al. (2006) described a nonconsanguineous Brazilian family with nonsyndromic occipital atretic cephalocele occurring in 6 individuals over 4 generations, with autosomal dominant inheritance and variable expressivity. The 12-year-old proband and his 4-year-old brother both had seizures from the first year of life, spastic gait, mental retardation with only a few or no words, hypertelorism, divergent strabismus, and midline cranial vertex alopecia with an occipital nodular mass. On brain imaging, the older sib had a 7 mm occipital bone defect associated with a small subcutaneous mass in continuity with the dura of the tentorium passing through the bone defect; the younger sib, who had undergone neurosurgical removal of an occipital nodular mass in infancy, had a 3 mm bone defect in the vertex. Associated intracranial abnormalities included frontoparietal schizencephaly, thinning of the corpus callosum, elevation of the straight sinus, periventricular leukomalacia-like lesions, enlargement of the magna cisterna, and a Dandy-Walker malformation in the posterior fossa. Their mother had normal cognitive function, a history of childhood strabismus and seizures, and an alopecic occipital soft tissue nodule; CT scan confirmed the presence of an occipital atretic cephalocele. Their maternal aunt and grandfather, who had no history of seizures, strabismus, neurologic symptoms, or nodular mass, both had a small occipital bone defect on brain imaging but no other CNS abnormality. The maternal great-grandmother had no history of seizures or neurologic symptoms but complained of a right parietal skull depression since childhood; CT scan showed partial absence of the external table and diploe of the parietal bone but no occipital lesion or other brain abnormality. Ghonge et al. (2011) reported an Indian family in which the proband was found to have an isolated occipital cephalocele on routine prenatal ultrasonography that was confirmed by MRI. The proband's father mentioned having a focal scalp lesion at a similar site, and examination revealed a small focal soft tissue bulge in the midline high occipital region, with overlying alopecia. CT scan showed a 3- to 4-mm poorly defined plaque-like lesion of soft tissue density, with prominent adjoining fat and a linear track-like region along the calvarial aspect. There was a linear, well-corticated calvarial defect in the underlying region measuring approximately 1 to 2 mm transversely, without a definite track in the intracranial region. In addition, the proband's paternal grandfather had a larger but similar scalp lesion with overlying alopecia. CT scan in the grandfather showed a large plaque-like lesion of soft tissue density measuring approximately 9 by 4 mm, beneath which there was a larger linear well-corticated calvarial defect measuring 4 mm transversely, with a definite linear track extending from the anterior aspect of the lesion across the calvarial defect and into the cranial cavity. The straight sinus and tentorium had an abnormal superior location with prominence of the superior cerebellar cistern, and there was a suggestion of fenestration of the dural sinus in the region of the confluence of the sinuses. In both the father and grandfather, the remainder of the cranial cavity and brain parenchyma were within normal limits. Ghonge et al. (2011) concluded that their lesions were consistent with atreticcephalocele. At birth, the proband had a small focal scalp swelling in the occipital location with alopecia of the overlying skin. Clinical examination, including a detailed neurologic examination, did not reveal any definite abnormality.
In the large 3-generation Vietnamese family with ADDWOC originally reported by Bassuk et al. (2004), Darbro et al. (2013) performed whole-exome capture and sequencing and identified a single heterozygous variant, a nonsense ... - Associations Pending Confirmation In the large 3-generation Vietnamese family with ADDWOC originally reported by Bassuk et al. (2004), Darbro et al. (2013) performed whole-exome capture and sequencing and identified a single heterozygous variant, a nonsense mutation in the NID1 gene (Q388X; 131390.0001), that segregated fully with disease in the family. Analysis of the NID1 gene in the Indian family with ADDWOC reported by Ghonge et al. (2011) did not reveal any mutations; however, Darbro et al. (2013) analyzed genes interacting with NID1 and identified a heterozygous missense mutation in LAMC1 (T746M; 150290.0001) that segregated with the phenotype. No functional analysis of the variants was reported.