Parietal bone agenesis with gracile bones and splenic hypoplasia/aplasia: Clinico‐pathologic report and differential diagnosis with review of cranio‐gracile bone syndromes, “osteocraniostenosis” and Kleeblattschädel

Spear, Gerald S.

doi:10.1002/ajmg.a.31473

Cited by 7 publications

(4 citation statements)

References 23 publications

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“…In 1994, Verloes and coworkers coined the name osteocraniostenosis (OCS [MIM 602361]) for a perinatally lethal condition characterized by gracile bones with thin diaphyses, premature closure of basal cranial sutures, and microphthalmia. [6][7][8] The name refers to the narrowing (''stenosis'') of the medullary cavity of the long bones and of the skull ( Figures 1E-1G and 2). In both KCS and OCS, skeletal radiology shows that bone density is increased, whereas the individ-ual skeletal elements are small and thin.…”

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confidence: 99%

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

Unger

Górna

Béchec

et al. 2013

The American Journal of Human Genetics

124

163

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Kenny-Caffey syndrome (KCS) and the similar but more severe osteocraniostenosis (OCS) are genetic conditions characterized by impaired skeletal development with small and dense bones, short stature, and primary hypoparathyroidism with hypocalcemia. We studied five individuals with KCS and five with OCS and found that all of them had heterozygous mutations in FAM111A. One mutation was identified in four unrelated individuals with KCS, and another one was identified in two unrelated individuals with OCS; all occurred de novo. Thus, OCS and KCS are allelic disorders of different severity. FAM111A codes for a 611 amino acid protein with homology to trypsin-like peptidases. Although FAM111A has been found to bind to the large T-antigen of SV40 and restrict viral replication, its native function is unknown. Molecular modeling of FAM111A shows that residues affected by KCS and OCS mutations do not map close to the active site but are clustered on a segment of the protein and are at, or close to, its outer surface, suggesting that the pathogenesis involves the interaction with as yet unidentified partner proteins rather than impaired catalysis. FAM111A appears to be crucial to a pathway that governs parathyroid hormone production, calcium homeostasis, and skeletal development and growth.

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mentioning

confidence: 99%

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

Unger

Górna

Béchec

et al. 2013

The American Journal of Human Genetics

124

163

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“…Along with the features revealed by prenatal ultrasound and babygram X-rays, the histological examination of bone growth plates is emerging as a very important criterion to support the diagnosis of OCS, as Spear et al reviewed [ 31 ]. Several of the examined cases showed varying degrees of growth plate irregularity, generally involving short/disorganized columns of pleomorphic chondrocytes in the proliferating and/or hypertrophic zone.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Molecular Diagnosis of Osteocraniostenosis in Fetuses and Newborns: Prenatal Ultrasound, Clinical, Radiological and Pathological Features

Rosato

Unger²,

Campos‐Xavier³

et al. 2022

Genes

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Osteocraniostenosis (OCS, OMIM #602361) is a severe, usually lethal condition characterized by gracile bones with thin diaphyses, a cloverleaf-shaped skull and splenic hypo/aplasia. The condition is caused by heterozygous mutations in the FAM111A gene and is allelic to the non-lethal, dominant disorder Kenny‐Caffey syndrome (KCS, OMIM #127000). Here we report two new cases of OCS, including one with a detailed pathological examination. We review the main diagnostic signs of OCS both before and after birth based on our observations and on the literature. We then review the current knowledge on the mutational spectrum of FAM111A associated with either OCS or KCS, including three novel variants, both from one of the OCS fetuses described here, and from further cases diagnosed at our centers. This report refines the previous knowledge on OCS and expands the mutational spectrum that results in either OCS or KCS.

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“…The bilateral parietal bone agenesis identified in this case has not previously been reported in retinoic acid embryopathy. Parietal bone agenesis is itself an exceedingly rare congenital anomaly, only reported a handful of times in the medical literature (de Heer, van Nesselrooij, Spliet, & Vermeij-Keers, 2003;Dunn, Stout, & Dix, 1991;Sela, Sahar, & Lewin-Epstein, 1979;Spear, 2006). One such report describes a female neonate who presented with right parietal bone agenesis, right temporal bone hypoplasia, and left parietal bone F I G U R E 3 Fetal autopsy images demonstrating bilateral parietal bone agenesis.…”

Section: Discussionmentioning

confidence: 99%

Parietal bone agenesis and athelia in retinoic acid embryopathy: An expansion of the phenotype

Yang

Wright

et al. 2021

Birth Defects Research

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Background: Retinoic acid signaling plays a critical role during embryogenesis and requires tight regulation. Exposure to exogenous retinoic acid during fetal development is known to have teratogenic effects, producing a recognizable embryopathy.Case: We describe a case of retinoic acid embryopathy secondary to maternal isotretinoin use until the ninth week of gestation and expand the phenotype to include the rare features of parietal bone agenesis and athelia. Histology of the parietal region showed fibrous tissue with no intramembranous ossification. The fetus also had multiple craniofacial dysmorphisms, thymic agenesis, and transposition of the great arteries with double outlet right ventricle and subaortic perimembranous ventricular septal defect. Neuropathology revealed enlarged ventricles with agenesis of the cerebellar vermis, focal duplication of the central canal and scattered parenchymal ependymal rests, and possible cerebral heterotopias with associated abnormal neuronal lamination. A chromosomal microarray was normal. Conclusion: Parietal bone agenesis and athelia are both rare congenital anomalies not previously reported in retinoic acid embryopathy. However, retinoic acid or its degrading enzyme has been demonstrated to exert effects in both of these developmental pathways, offering biological plausibility. We propose that this case may represent an expansion of the phenotype of retinoic embryopathy.

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Parietal bone agenesis with gracile bones and splenic hypoplasia/aplasia: Clinico‐pathologic report and differential diagnosis with review of cranio‐gracile bone syndromes, “osteocraniostenosis” and Kleeblattschädel

Cited by 7 publications

References 23 publications

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

FAM111A Mutations Result in Hypoparathyroidism and Impaired Skeletal Development

Clinical and Molecular Diagnosis of Osteocraniostenosis in Fetuses and Newborns: Prenatal Ultrasound, Clinical, Radiological and Pathological Features

Parietal bone agenesis and athelia in retinoic acid embryopathy: An expansion of the phenotype

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