The Tomographic Study and the Phenotype of Wormian Bones

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by progressive osteolysis involving the carpal and tarsal bones, and often associated with nephropathy. It is caused by heterozygous mutation in the MAF bZIP transcription factor B (MAFB) gene. Heterogeneous clinical manifestation and wide spectrum of disease severity have been observed in patients with MCTO. Here, we report a case of a male patient who presented with kidney failure in childhood with progressive disabling skeletal deformity. He was diagnosed with MCTO at 31-years-old, where a de novo pathogenic heterozygous variant in NM_005461.5:c.212C>A: p.(Pro71His) of the MAFB gene was identified. While there has been little data on the long-term prognosis and life expectancy of this disease, this case report sheds light on the debilitating disease course with multiple significant morbidities of a patient with MCTO throughout his lifetime of 33 years.

This study aimed to investigate the incidence, topographical distribution, morphology, and interrelationship of the metopism and Wormian bones (WBs) in dry adult-Chinese skulls. In this study, 285 dried adult-Chinese skull specimens from the Department of Anatomy at the Southern Medical University were examined. The incidence of different types of metopism and WBs were recorded. The length of the metopic suture was measured using a flexible ruler. Additionally, the lengths and widths of the WBs were measured using a vernier calliper. The incidence of metopism and WBs in Chinese adults were estimated at 10.18% (29/285) and 63.86% (182/285), respectively. The metopism always accompanied WBs (26/29, 89.66%), but the WBs did not necessarily accompany metopism (26/182, 14.29%). The locations of the WBs in the order of decreasing incidence were the lambdoid suture (78.57%, 143/182), pterion (34.62%, 63/182), asterion (12.09%, 22/182), lambda (8.24%, 15/182), sagittal suture (4.95%, 9/182), and Inca bone (3.85%, 7/182). These locations differed in topographical distribution and morphological patterns. Chinese adults differ in incidence of metopism and WBs from adults of other races, indicating racial differences. The characteristics of WBs vary depending on the cranial site of occurrence. The metopism always accompanies WBs, but the WBs do not necessarily accompany metopism.

Introduction and Aim: Wormian bones vary in size, form and quantity and their occurrence is influenced by both genetic and environmental variables. Wormian bones are also seen in foetus ultrasounds during the antenatal period. The occurrence of much more than one sutural bone at the pterion is radiographically significant. The current study aims at the occurrence and topography of Wormian bones in the Telangana region and correlates them to other population groups. Material and Methods: This study was carried out in 160 dry adult human skulls. Presence of these Wormian bones in sagittal, coronal, and Lambdoid sutures along with bregma, lambda, asterion and pterion were noted. The quantitative data is analyzed, and the images were captured. Results: Their incidence was 45 % while in 55% skulls they were absent. Their percentage was more in lambdoid suture (16.9%) followed by asterion (12.5%). They were also observed in sutures like coronal (5.6%) and sagittal (1.9%). In pterion their occurrence was 3.12%. In bregma, none of the skull showed Wormian bones. Conclusion: In the present study, incidence of Wormian bones (Wb’s) is 45% with a greater number of Wb’s observed in Lambdoid suture (16.9%). In the event of any interventions or investigations on the skull, topography of these bones is to be considered.

Over the years a number of investigators have analysed the morphology of wormian bones in different population groups across the world. There have been significant variations between findings reported in these studies, and this has prompted researchers to focus on the influence of genetic factors on the morphology of these bones. In the light of the above observation, we considered it justified to conduct anatomical studies on wormian bones in different population groups; hence, we undertook the present study to look into the morphological details of these bones among a population in the eastern part of India. We observed a total of 120 adult dry human skulls of unknown age and sex, and noted the anatomical details of wormian bones when present. It was observed that wormian bones were present in 45% of skulls, and that 30% of skulls had more than one wormian bone. We also found that 2.5% of the skulls had ten or more wormian bones, which is considered as pathognomonic. Maximum incidence (53.33%) was observed at the lambdoid suture and minimum incidence at the bregma and metopic suture (0.61% in each case). We noted a high incidence (21.21%) of Inca bone/lambdoid ossicle, and bilaterally symmetrical wormian bones were present in 12.5% study skulls. There were statistically significant (P<0.05) variations between the findings of the present study and values reported in previous studies conducted in other regions of India and different parts of the world. Our observations favour the view that genetic influence primarily determines the morphology of wormian bones.

Introduction Osteogenesis imperfecta (OI) is a human genetic disorder of increased bone fragility and low bone mass. Severity varies widely, ranging from intrauterine fractures and perinatal lethality to very mild forms without fractures. There is variable association of typical extra skeletal manifestations with the disorder, including blue sclera, dentinogenesis imperfecta, hyperlaxity of ligaments and skin, hearing impairment and the presence of Wormian bones on skull radiography1. The most widely used classification of OI distinguished four clinical types2. The most relevant clinical characteristic of all OI t-ypes is bone fragility, the severity of which increases in the order type I < type IV < type III < type II. It is now w-idely recognized that there may be m-any more types of OI than those class-ified by Sillence et al. Some forms of congenital brittle bones have been considered OI and have been added as types V, VI and VII3–5. There is still no perfect consensus about the definition of OI. Plotkin recently proposed defining OI as syndromes resulting from mutations in either COL1A1 or COL1A2 genes, and to group all other syndromes with congenital brittle bones as ‘syndromes resembling OI (SROI)’, pending the identification of their causal mutations6. In the new Nosology and Classification of the Genetic Skeletal disorders7, OI is declined in several forms depending on the severity of the phenotype, whatever the mode of the transmission or the gene involved. We first review the genetic mutations implicated in the eight different types of OI, then, the craniofacial consequences of OI mutations are summarized. * Corresponding author Email: mgoldberg.goldberg004@gmail.com

The material of the study was the skull of an 8-year-old girl. In the cranioscopy, the following were identified: on the right side, the bone of the sphenoid fontanel or epipteric bone; bones of lambdoid suture - on the right side in the amount of 5, on the left side -1 bone; preinterparietal bone, ospreinterparietale.By the craniometric method, the height and width of the bones were determined. The bone of the sphenoid fontanelle or epipteric bone is located between the frontal, parietal bones, the greater wing of the sphenoid bone, and the squama of the temporal bone. The width of the epipteric bone is 16.5 mm, height 9.5 mm. The bones of the lambdoid suture in the amount of 5 on the right and the 1st on the left were located in an elongated state.The largest bone was located in the middle of the right lambdoid suture; apparently, it was formed by the union of at least two Wormian bones. Preinterparietal bone has a triangular shape, the base of the triangle facing the sagittal suture, the tip, slightly rounded - in the direction of the occipital bone. The lateral angles of the preinterparietal bone are serrated, which, in principle, clearly distinguishes it from the parietal bones. The bone was single, no sutures or grooves dividing the preinterparietal bone into parts were observed. The width of the bone is 18.5 mm, height 13.8 mm.

PurposeWormian bones (WB) are accessory ossicles that develop within cranial sutures. While typically benign, their presence in large numbers has been associated with various genetic and developmental disorders. This study aims to characterize the prevalence, anatomical distribution, and clinical associations of WB in a pediatric population undergoing cranial CT imaging.MethodsA retrospective review was conducted at Monroe Carell Jr. Children’s Hospital at Vanderbilt. Pediatric patients aged 0 to 18 years who underwent cranial CT imaging for any clinical indication were included. WB were radiologically confirmed, and demographic data, cephalic index, and comorbidities were collected and analyzed.ResultsAmong the 13,519 patients who underwent cranial CT imaging, 77 (0.57%) had radiologically confirmed WB, totaling 476 ossicles. The prevalence increased to 2.1% when examining our clinic cohort over a 5-year period. The lambdoid suture was the most common site (343/476, 72.1%), followed by the posterior fontanelle (53/476, 11.1%). Multiple WB (≥ 2) represented the most common phenotype (52/77, 67.5% of cases), and 13 patients (16.8%) had at least one associated skeletal or craniofacial condition, most commonly craniosynostosis (10/13, 76.9%). Cephalic index analysis demonstrated a predominance of brachycephaly (54/77, 70.1%).ConclusionThis study presents a comprehensive evaluation of WB in a large pediatric cohort. WB may co-exist with craniosynostosis or other skeletal conditions such as osteogenesis imperfecta. Given the greater prevalence of WB compared to craniosynostosis (2.1%: clinic cohort & 0.57%: institutional cohort vs. 0.05%), clinicians should consider WB in the differential diagnosis of abnormal head shape in infancy, particularly in a subspecialist practice.

BackgroundWormian, or sutural bones, are additional, irregularly shaped bone fragments that can occur within cranial sutures. These bones may arise due to various factors, including mechanical pressure on skull bones during early ontogenetic stages, such as during artificial cranial deformations, or due to genetic and environmental influences. This study investigates the potential genetic basis of sutural bones by comparing their frequencies across diverse global regions. It analyzed 33 craniological series, encompassing 2059 crania, to assess the frequency of sutural bones in the coronal, squamous, lambdoid, and occipitomastoid sutures among skeletal populations from regions including Aboriginal Australia, Melanesia, Southeast Asia, Siberia, Europe, and Native America. Biological distances between populations were calculated using Smith’s mean measure of divergence (MMD), with results visualized through multidimensional scaling.ResultsThe analysis identified distinct clusters of Caucasian and Siberian populations. Siberian aboriginal populations are compactly grouped, consistent with mtDNA data indicating genetic roots dating back to the Neolithic inhabitants of the Lake Baikal region. Further, differentiation within these populations is linked to the founder effect and gene flow. Notably, genetically related groups like the Inuit and Chukchi of Chukotka differ from other Siberian groups. In contrast, southern Siberian populations, such as the Buryats and Mongols, are closely positioned, aligning with genetic data. The differentiation between Southeast Asian and African regions was subtler, with their clusters largely overlapping. Yet, genetic links between populations were observed in some cases. Thus, Australians, Melanesians, and Papua New Guineans were located close to each other on the multidimensional scaling map, as were two African populations.ConclusionsThe findings tentatively suggest a potential genetic component in the expression of Wormian bones, although this hypothesis requires further empirical support, particularly through genetic studies. While genetic factors may influence the expression of Wormian bones, environmental conditions and pathological processes also play significant roles. It can be suggested that Wormian bones could potentially serve as an additional tool in kinship analysis within burials; however, their utility significantly depends on the extent of their genetic influence. If future genetic studies confirm a substantial genetic component and its dominance over environmental factors, the use of these bones in anthropological and forensic analyses would receive additional validation.

We aimed to understand the etiology behind the abnormal craniofacial contour and other clinical presentations in a number of children with Robinow syndrome. Seven children with Robinow syndrome were enrolled in this study (autosomal recessive caused by homozygous mutations in the ROR2 gene on chromosome 9q22, and the autosomal dominant caused by heterozygous mutation in the WNT5A gene on chromosome 3p14). In the autosomal recessive (AR) group, the main clinical presentations were intellectual, disability, poor schooling achievement, episodes of headache/migraine, and poor fine motor coordinative skills, in addition to massive restrictions of the spine biomechanics causing effectively the development of kyposcoliosis and frequent bouts of respiratory infections. Three-dimensional reconstruction computed tomography scan revealed early closure of the metopic and the squamosal sutures of skull bones. Massive spinal malsegmentation and unsegmented spinal bar were noted in the AR group. In addition to severe mesomelia and camptodactyly, in the autosomal dominant (AD) group, no craniosynostosis but few Wormian bones and the spine showed limited malsegemetation, and no mesomelia or camptodactyly have been noted. We wish to stress that little information is available in the literature regarding the exact pathology of the cranial bones, axial, and appendicular malformations in correlation with the variable clinical presentations in patients with the 2 types of Robinow syndrome.

The article presents the modern views of clinicians and geneticists on one of the most severe genetic disorders of skeletal and connective tissues - osteogenesis imperfecta. The review provided the literature data that showed the incidence rates, genetic heterogeneity of osteogenesis imperfecta, as well as the role of some proteins involved in the construction of bone tissue, as well as a clinical classification of the main types of the disorder. The authors described a clinical case: a girl with typical clinical and radiological manifestations of the rarest of all types of osteogenesis imperfecta - type II (perinatal-lethal, congenital osteogenesis imperfecta, Vrolik’s syndrome). The child’s diagnosis was verified by a parallel DNA sequence analysis which showed a heterozygous mutation in exon 29 (c.1966G&gt; A) of COL1A1 gene not previously described in the literature. It caused the substitution of glycine for serine at position 656. The role of antenatal diagnostics and the importance of medical genetic counselling of the family before planning the next pregnancy due to the existing risk of re-birth of a sick child is outlined. Due to the fact that majority of the patients with the most prognostically unfavourable type II osteogenesis imperfecta, as a rule, die in utero, the described case of observation of the girl with typical clinical and X-ray signs of the disorder for almost 3 months of postpartum period is extremely rare and highly indicative. The detection of the heterozygous mutation in exon 29 (c.1966G &gt; A) of COL1A1 gene by a parallel DNA sequence analysis which was not previously described in the literature gives an additional significance to the described observation.

A Single Recurrent Mutation in the 5′-UTR of IFITM5 Causes Osteogenesis Imperfecta Type V

Maya adult crania from the site of Lamanai, Belize provide a retrospective means of examining growth processes in the cranial vault. The Lamanai population practiced fronto-occipital deformation which is found to be significantly associated with premature sagittal synostosis and wormian bones of the lambdoidal suture. The undeformed members of the population also exhibit an abnormally high frequency of sagittal synostosis, but a significantly lower frequency than the deformed sample. It is suggested that the deforming apparatus creates tensile forces on the sagittal suture during the peak period of growth of the parietals, and that these forces might induce an adaptive response important in producing premature sagittal synostosis. The undeformed sample may have an increased congenital risk of sagittal synostosis created by their natural brachycephalic morphology in utero. The frequency patterning of wormian bones suggests a mixture of genetic and environmental causes in which tensile forces may also play a role.

Os Inca, also known as interparietal bones, are supernumerary bones found in the interparietal region of the occipital bone, adjacent to the lambdoid suture. They are found due to incomplete fusion of the ossification centres of the interparietal region of the squamous part of occipital bone. In the present case, two such additional ovoid bones were seen in the skull, immediately to the right of the apex of the occipital squamosa, intervening between the occipital and the right parietal bones. These two bones, identified as interparietal bones, were articulated by interdigitating sutures, to both of the adjacent bones as well as to each other. The presence of such bones is common in lower animals including lower mammals like rodents and marsupials but is rare in man. Os Incae have considerable clinical significance because they can be mistaken for fracture fragments during skull roentgenogram as well as during medico-legal autopsies. Besides, they can pose as a problem during neurosurgery. Sexual dimorphism, race and ethnicity cause significant variations in their incidence and hence, they are of considerable interest to anthropologists.

To date, only three compound heterozygous mutations in the SEC24D gene have been found to cause recessively inherited forms of OI. We sought to characterize the phenotypes and to identify the SEC24D gene mutations associated with Chinese families with OI. Using whole-exome sequencing in two probands, we identified two novel compound heterozygous mutations in SEC24D. In family 1, the proband was a 23-year-old male; he had recurrent fractures and dentinogenesis imperfecta. His anterior fontanel was not closed, and he showed facial dysmorphism. A computed tomography three-dimensional imaging of the cranium showed skull deformities associated with a broad ossification defect in the frontoapical area, a widened sagittal suture, and Wormian bones. In family 2, the proband was a 7-year-old boy, who also had recurrent fractures and dentinogenesis imperfecta. His anterior fontanel was not closed, and he did not have obvious facial dysmorphism. We identified one novel compound heterozygous missense substitution in the proband in family 1, including c.2723G>A (p. Cys908Tyr) and c.2842T>C (p. Ser948Pro). In the proband in family 2, we identified another novel compound heterozygous missense substitution, including c.938G>A (p. Arg313His) and c.875C>T (p. Pro292Leu). We discovered two novel compound SEC24D mutations of autosomal recessive OI patients. Our study extended both the phenotypic and the genotypic spectrum of the autosomal recessive OI patients with SEC24D mutations.

To explore the therapeutic efficacy of L-glutamine (L-Gln) on pathological progression and clinical symptoms of osteoarthritis (OA), and compare with glucosamine sulfate (GS), and celecoxib (CXB). Rats were administered sodium chloride, L-Gln, GS, or CXB via gavage for eight weeks starting from the fifth week after sham operation or Anterior Cruciate Ligament Transection (ACLT) + Medial Meniscectomy (MMx). Then the severity of knee OA in rats was evaluated by serological analysis, histological examination and imaging examination. In addition, patients with mild primary OA were administered L-Gln, GS, or CXB orally for 12 weeks in accordance with the randomization principle. The efficacy end points were the change from baseline to week 24 in the pain and physical function subscale scores of the Western Ontario and McMaster Universities OA Index (WOMAC), and Lequesne score. Treatment with L-Gln alleviated the increased concentration of serum cartilage degradation markers caused by OA in rats. Histological tests showed improvement in knee joint cartilage destruction after treatment. Three-dimensional CT scans and reconstructions revealed a reduction in osteophyte formation and subchondral bone loss. L-glutamine performed as well as or better than glucosamine sulfate and celecoxib in all comparative measures among the three treatment groups. In clinical trials, the WOMAC pain and physical function subscale scores, as well as the Lequesne score, decreased from baseline in all three patient groups during follow-up, with no significant differences observed between the groups. Our research indicates that L-Gln is comparable to GS and CXB in improving the pathological progression and clinical efficacy of OA, which makes it a promising drug for the treatment of osteoarthritis.