Delayed membranous ossification of the cranium associated with familial translocation (2;3)(p15;q12)

Abstract

The relationship of delayed membranous cranial ossification to cranium bifidum and parietal foramina syndromes is unclear. We report on a family with delayed cranial membranous ossification (OMIM 155980) that segregates with an apparently balanced reciprocal translocation between chromosomes 2 and 3. The propositus had apparently low-set ears, proptosis, and a soft skull at birth. A radiographic survey of the skeleton showed markedly decreased ossification of the cranial bones and no other skeletal abnormalities. The mother and maternal grandmother of the propositus have brachycephaly, hypertelorism, and a history of a soft skull at birth. Chromosome analysis of peripheral blood from the propositus showed 46,XY,t(2;3)(p15;q12). The propositus, mother, and grandmother carry the same reciprocal translocation, whereas the mother's two phenotypically normal sibs have a normal karyotype. We used an STS-linked BAC resource to define the translocation breakpoint by identifying flanking BAC clones from both chromosomes 2, 1006D24 (D2S2279) and 1060A5 (D2S2231), and chromosome 3, 3D17 (WI8558) and 3D18 [CITB Human BAC Library, J.R.K.]. This represents the second report of a family with delayed membranous ossification of the cranium and the first report of the phenotype segregating with a chromosome rearrangement.

Targeted Disruption of the Mn1 Oncogene Results in Severe Defects in Development of Membranous Bones of the Cranial Skeleton

“…In humans no syndromes are known that resemble the abnormalities seen in Mn1 knockout mice. Defects in membranous bones are rare; only two papers describe families with delayed intramembranous ossification (3,6). During infancy, these patients show a complete lack of ossification of the calvarial bones forming the roof of the skull resulting in a soft skull.…”

Characterization of complex chromosomal rearrangements by targeted capture and next-generation sequencing

“…Patient 1 Cargile et al (2000) previously described this family (Fig. 4) in which delayed cranial membranous ossification (OMIM 155980) co-segregates with an ABT 46,XY,t(2;3)(p15;q12).…”

“…We refer to this approach as translocation breakpoint capture followed by next-generation sequencing (TBCS) and tested it in three patients with dysmorphic syndromes and complex chromosomal translocations: The first has craniofacial abnormalities and an apparently balanced t(2;3)(p15;q12) translocation that co-segregates with the phenotype in three generations (Cargile et al 2000); the second has cleidocranial dysplasia (CCD; OMIM 119600) associated with a t(2;6)(q22;p12.3) translocation and a breakpoint in RUNX2 on chromosome 6p; and the third has acampomelic campomelic dysplasia (OMIM 114290) associated with a t(5;17)(q23.2;q24) translocation, with a breakpoint in the region upstream of SOX9 on chromosome 17q. Preliminary studies (see below) predicted complex rearrangements in patients 1 and 3 with a total of 10 predicted breakpoints in the three patients.…”

An unusual aperture in a child's calvaria from western Central Asia: differential diagnoses

“…This is a congenital cleft of the calvaria without associated abnormality of the brain or meninges, and is generally asymptomatic (Menkes, 1995). Persistence of the fontanelles is sometimes accompanied by cleidocranial dysostosis (see above) (Menkes, 1995;Cargile et al, 2000). Given that the lesion extends into the frontal bone, it is possible that it pertains to a defect in the fusion of the metopic suture.…”