CDK10 Mutations in Humans and Mice Cause Severe Growth Retardation, Spine Malformations, and Developmental Delays.

In five separate families, we identified nine individuals affected by a previously unidentified syndrome characterized by growth retardation, spine malformation, facial dysmorphisms, and developmental delays. Using homozygosity mapping, array CGH, and exome sequencing, we uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease. CDK10 is a protein kinase that partners with cyclin M to phosphorylate substrates such as ETS2 and PKN2 in order to modulate cellular growth. To validate and model the pathogenicity of these CDK10 germline mutations, we generated conditional-knockout mice. Homozygous Cdk10-knockout mice died postnatally with severe growth retardation, skeletal defects, and kidney and lung abnormalities, symptoms that partly resemble the disease's effect in humans. Fibroblasts derived from affected individuals and Cdk10-knockout mouse embryonic fibroblasts (MEFs) proliferated normally; however, Cdk10-knockout MEFs developed longer cilia. Comparative transcriptomic analysis of mutant and wild-type mouse organs revealed lipid metabolic changes consistent with growth impairment and altered ciliogenesis in the absence of CDK10. Our results document the CDK10 loss-of-function phenotype and point to a function for CDK10 in transducing signals received at the primary cilia to sustain embryonic and postnatal development.

Distinctive spine abnormalities in patients with Goldenhar syndrome: tomographic assessment.

PURPOSE: Goldenhar syndrome consists of a combination of unilateral auricular appendages, auricular fistulas, and ocular epibulbar dermoids combined with a unilateral underdevelopment of the craniofacial structures and vertebral abnormalities. We aimed to elicit the underlying spine pathology in a group of patients via tomographic assessment. MATERIALS AND METHODS: Hemifacial microsomia, cranial asymmetry, multiple ear tags, skin tags around the mouth and microtia were the most prominent facial features encountered in six patients with Goldenhar syndrome. Torticollis and cervico-thoracic scoliosis were the major deformities encountered in all patients. Thoraco-lumbar scoliosis and kyphoscoliosis were of lesser occurrence. Tomographic studies have been applied to all patients to delineate the underlying pathology. RESULTS: Diverse spectrum of distinctive spine anomalies has been identified. Malsegmentation of the skull base associated with diffuse fusion with the upper cervical vertebrae was the most common spine pathology. Bilateral failure of segmentation, unilateral unsegmented bar and failure of vertebral formation were of lesser occurrence. Strikingly, we observed that the side of the hemifacial microsomia is strongly correlated with that of the craniocervical and the cervical vertebral abnormalities. CONCLUSION: The importance of this paper is threefold; first, little information is available in the literature regarding the magnitude and the diversity of spine pathology in patients with Goldenhar syndrome. Second, is to alert spine specialists that conventional radiographic assessment of the craniocervical area is an insufficient modality to assess children with syndromic associations. Third, a rotation and flexion deformity of the neck associated with facial asymmetry and/or plagiocephaly should be considered as a syndromic entity rather than a simple physiological deformation.

Radiographic and Tomographic Study of the Cranial Bones in Children with the Idiopathic Type of West Syndrome.

BACKGROUND: Neither radiological phenotypic characteristics nor reconstruction CT scan has been used to study the early anatomical disruption of the cranial bone in children with the so-called idiopathic type of West syndrome. MATERIAL AND METHODS: The basic diagnostic measures and the classical antiepileptic treatments were applied to these children in accordance with the conventional protocol of investigations and treatment for children with West syndrome. Boys from three unrelated families were given the diagnosis of the idiopathic type of West syndrome, aged 7, 10 and 12 years old. Parents underwent extensive clinical examinations. Three parents (age range of 28-41 year) were included in this study. All children showed a history of intellectual disabilities, cryptogenic epileptic spasms and fragmented hypsarrhythmia. These children and their parents were referred to our orthopedic departments because of variable skeletal deformities. Variable forms of skeletal deformities were the motive for the families to seek orthopedic advice. A constellation of flat foot, torticollis and early-onset osteoarthritis were observed by the family doctor. Apparently, and from the first clinical session in our practice, we felt that all these children are manifesting variable forms of abnormal craniofacial contour. Thereby, we immediately performed detailed cranial radiological phenotypic characterization of every affected child, as well as the siblings and parents, and all were enrolled in this study. All affected children underwent whole-exome sequence analysis. RESULTS: The craniofacial phenotype of all children revealed apparent developmental anatomical disruption of the cranial bones. Palpation of the skull bones showed unusual palpable bony ridges along different sutural locations. A 7-year-old child showed abnormal bulging over the sagittal suture, associated with bilateral bony ridges over the squamosal sutures. AP skull radiograph of a 7-year-old boy with West syndrome showed facial asymmetry with early closure of the metopic suture, and other sutures seemed ill-defined. A 3D reconstruction CT scan of the skull showed early closure of the metopic suture. Another 3D reconstruction CT scan of the skull while the patient was in flexion showed early closure of the squamosal sutures, pressing the brain contents upward, causing the development of a prominent bulge at the top of the mid-sagittal suture. A reformatted 3D reconstruction CT scan confirmed the bilateral closure of the squamosal suture. Examination of the parents revealed a similar skull radiographic abnormality in his mother. A 3D reformatted frontal cranial CT of a 35-year-old mother showed early closure of the metopic and sagittal sutures, causing a mid-sagittal bony bulge. A 10-year-old boy showed an extremely narrow frontal area, facial asymmetry and a well palpable ridge over the lambdoid sutures. A 3D axial reconstruction CT scan of a 10-year-old boy with West syndrome illustrated the asymmetry of the posterior cranial bones along the lambdoid sutures. Interestingly, his 28-year-old mother has been a client at the department of spine surgery since she was 14 years old. A 3D reconstruction CT scan of the mother showed a noticeable bony ridge extending from the metopic suture upwards to involve the sagittal suture (red arrow heads). The black arrow shows a well demarcated bony ridge over the squamosal suture. A 3D reconstruction CT scan of the skull and spine showed the thick bony ridge of the metopic and the anterior sagittal as well as bilateral involvement of the squamosal, causing apparent anterior narrowing of the craniofacial contour. Note the lumbar scoliosis. A 12-year-old boy showed brachycephaly. A lateral skull radiograph of a 12-year-old boy with West syndrome showed premature sutural fusion, begetting an abnormal growth pattern, resulting in cranial deformity. The nature of the deformity depends on which sutures are involved, the time of onset and the sequence in which individual sutures fuse. In this child, brachycephalic secondary to craniosynostosis, which occurred because of bilateral early ossification of the coronal sutures, led to bi-coronal craniosynostosis. Thickened frontal bones and an ossified interclinoid ligament of the sella turcica were encountered. The lateral skull radiograph of a 38-year-old mother with a history of poor schooling achievements showed a very similar cranial contour of brachycephaly, thickening of the frontal bones and massive ossification of the clinoid ligament of the sella turcica. Maternal history revealed a history of multiple spontaneous miscarriages in the first trimester of more than five times. Investigating his parents revealed a brachycephalic mother with borderline intelligence. We affirm that the pattern of inheritance in the three boys was compatible with the X-linked recessive pattern of inheritance. Whole-exome sequencing showed non-definite phenotype/genotype correlation. CONCLUSIONS: The aim of this study was sixfold: firstly, to refute the common usage of the term idiopathic; secondly, we feel that it could be possible that West syndrome is a symptom complex rather than a separate diagnostic entity; thirdly, to further detect the genetic carrier, we explored the connection between the cranial bones in children with West syndrome with what has been clinically observed in their parents; fourthly, the early life anatomical disruptions of the cranial bones among these children seem to be heterogeneous; fifthly, it shows that the progressive deceleration in the development of this group of children is highly connected to the progressive closure of the cranial sutures; sixthly, we affirm that our findings are novel.

Dysmorphic facies and diffuse posterior spine ankylosis in a patient with unusual form of spondyloenchondrodysplasia (Spranger type IV).

We describe a male patient, who was seen for the first time at the age of 8 years because of short trunk dwarfism. Spine radiographs showed platyspondyly with irregular areas of increased and decreased mineralization (irregular spotted appearance within lytic lesions located along the posterior vertebral bodies of the entire spine). Skeletal survey showed no enchondromatous lesions of the short/long tubular bones. At the age of 17, progressive spine stiffness associated with stooping posture developed. 3DCT scanning showed pathological transformation of the spinal enchondromas into generalized ossification and thickening of the posterior vertebral elements (vertebral laminae, supraspinal, and interspinal ligaments, respectively) causing effectively the development of a diffuse posterior spinal ankylosis. We report what might be a unique subtype of spondyloenchondrodysplasia (Spranger type IV).

The Tomographic Study and the Phenotype of Wormian Bones.

BACKGROUND: We describe patients who were recognized via conventional radiographs of the skull as manifesting wormian bones. Wormian bones are not a specific diagnostic entity and can be seen in variable forms of syndromic disorders. MATERIALS AND METHODS: Seven children and three adults (of 10-28 years) were seen and diagnosed in our departments. The principal complaints for the pediatric and adult group were: ligamentous hyperlaxity, a history of delayed walking and occasional fractures, which later in life started to manifest a constellation of neurological symptoms such as nystagmus, persistent headache, and apnea. Conventional radiographs were the first traditional tools used to recognize wormian bones. We performed 3D reconstruction CT scans to further understand the precise etiology and the nature of these wormian bones and attempted to connect them with a broad spectrum of unpleasant clinical presentations. Our group of patients was consistent with the phenotypic and genotypic diagnoses of osteogenesis imperfecta type I and type IV as well as patients with multicentric carpotarsal osteolysis syndrome. RESULTS: Three-dimensional reconstruction CT scan of the skulls confirmed that these worm-like phenotypes are in fact stemmed from the progressive softening of the sutures. The overall phenotype of the melted sutures is akin to overly stretched pastry. The most concerning sutures in this pathological process are the lambdoid. The overstretching of the lambdoid sutures was responsible for the development of sub-clinical basilar impression/invagination. Patients with certain forms of skeletal dysplasia such as osteogenesis imperfecta type I and IV manifested the heterozygous mutation of COL1A1/COLA2, shown as typical overstretching of the sutures. Similarly, patients with multicentric carpotarsal osteolysis syndrome with a heterozygous missense mutation of MAFB also manifested the phenotype of overly stretched pastry along the skull sutures. CONCLUSION: What we encountered via 3D reconstruction CT scan in our group of patients was entirely different than the traditional description that can be found in all relevant literature of the last decades. The worm-like phenomenon is in fact a pathological sequel occurring as a result of a progressive softening of the sutures, which results in the overstretching of the lambdoid sutures, a pathological process roughly similar to an overly stretched soft pastry. This softening is totally connected to the weight of the cerebrum (the occipital lobe of the cerebrum). The lambdoid sutures represent the weight-bearing zone of the skull. When these joints are loose and soft, they adversely alter the anatomical structures of the skull and lead to a highly hazardous derangement of the craniocervical junction. The latter causes the pathological upward invasion of the dens into the brain stem, leading to the development of morbid/mortal basilar impression/invagination.

Cutaneous, Cranial, and Skeletal Defects in Children and Adults with Focal Dermal Hypoplasia.

BACKGROUND: The diagnostic process for children and adults manifesting a constellation of ectodermal abnormalities requires a conscientious and highly structured process. MATERIAL AND METHODS: Six girls (aged 6-month-8 years) and two older girls (aged 13 and 16 years) were born with variable skin lesions of varying intensities associated with noticeable cranial and skeletal malformation complexes. Cleft palate, abnormal dentition, and multiple papillomas were evident around the mouth, mostly bilateral but asymmetrical in the upper and lower limbs. Exaggerated frontal bossing (macrocephaly) and in some patients' microcephaly with variable skeletal defects of the craniocervical junction and diverse forms of lower limb deformities of syndactyly, polydactyly, and split-hand/foot (ectrodactyly). RESULTS: All patients manifested the constellation of abnormalities with variable intensities ranging between alopecia, papillomas, striated skin pigmentations split-hand/foot (ectrodactyly), and major bone defects. A 3D reconstruction CT scan was directed mainly to further scrutinize children with pseudo cleft lip, submucus cleft, and cleft palate. Interstingly, they manifested massive demineralization of the cranium associated with severely defective dentition. A spine 3D reconstruction CT scan in two girls showed marked cystic cavitation of the upper jaw associated with excessive cavitation of the mastoid, causing tremendous frailty of the mastoid bone. A 3D sagittal CT scan showed odontoid hypoplasia and C1-2 instability associated with the rudimentary atlas and the persistence of extensive synchondrosis of the cervico-thoracic spine. The overall clinical and radiological phenotypic characterizations were consistent with the diagnosis of focal dermal hypoplasia (Goltz syndrome). Two children manifested heterozygous mutations in the PORCN gene, chromosome Xp11. CONCLUSIONS: In this study, we believe it's a good opportunity to share our novel scientific findings, which are intriguing and can be inspiring to readers, and to further aid the current scientific literature with exceptionally new unveiling results. This is the first comprehensive study of the cranio-skeletal malformation complex in children with GS.

Craniofacial Malformations as Fundamental Diagnostic Tools in Syndromic Entities.

Background: A long list of syndromic entities can be diagnosed immediately through scrutinizing the clinical phenotype of the craniofacial features. The latter should be assisted via proper radiological interpretations. Patients and Methods: Different children aged from 1 month to 12 years were referred to our departments seeking orthopedic advice. Primarily, all received variable false diagnoses in other institutes. Two unrelated boys of one month and 12 months were falsely diagnosed as having positional plagiocephaly associated with contractures of idiopathic origin. Two unrelated boys of 14 months and 2 years were diagnosed with pseudo-hydrocephalus and non-specific syndrome, and were referred to explore their skeletal development. Two unrelated girls of 4 years old and 12 years old presented with multiple contractures were referred because of progressive scoliosis. A 4-year-old girl was referred with a false provisional diagnosis of facial diplegia. All children underwent detailed clinical, radiological and tomographic phenotypic characterizations and genetic testing, respectively. Results: Idaho syndrome (craniosynostosis associated with multiple dislocations) was the final diagnosis in the two unrelated boys with plagiocephaly and multiple contractures. Two children falsely diagnosed with pseudo-hydrocephalus and non-specific syndrome, were diagnosed with Silver-Russell syndrome (RSS). Contractural arachnodactyly Beals (CAB) was confirmed as the definitive diagnosis in the two unrelated girls with progressive scoliosis and multiple contractures. Parry-Romberg syndrome (PRS) associated with congenital lumbar kyphosis was the final diagnosis of the girl with the diagnosis of facial diplegia. Hypomethylation of ICR1 was confirmed in the RSS patients. Whole exome sequencing (WES) revealed a heterozygous mutation in the PRS patients. WES and array-CGH showed that no relevant variants or copy number variations (CNV) were identified in the CAB patients. Conclusions: On the one hand, newborn children can manifest diverse forms of abnormal craniofacial features, which are usually associated with either major or minor dysmorphic stigmata. A cleft lip/ palate is a major craniofacial malformation, and frontal bossing or a disproportionate craniofacial contour can be falsely considered as a transient plagiocephaly, which is spontaneously resolved by time. On the other hand, many physicians fall into the problem of deeming a countless number of diseases, such as contractures, as an idiopathic or non-specific syndrome. The latter stems from limited clinical experience. Therefore, failing to establish between the onset of the deformity and other inexplicit abnormal features that the patient or their immediate families or relatives carry is the final outcome. In this study, we used, for the first time, a reconstruction CT scan to further delineate the congenital disruption of the craniofacial anatomy and the other skeletal malformation complex.

Occipitoatlantoaxial junction malformation and early onset senile ankylosing vertebral hyperostosis in a girl with MURCS association.

Recent onset of head mobility limitations associated with significant stiffness along the vertebral column were the predominating symptomatology in a girl with MURCS association. Occipitoatlantoaxial junction malformation complex and vertebral hyperostosis have been identified. Three-dimensional computerized tomography (3-DCT) scan showed assimilation of the anterior arch of the atlas causing basilar invagination. She also had significant thoracic vertebral hyperostosis closely resembling senile ankylosing vertebral hyperostosis (Forestier disease). We report on what might be a novel constellation of spine maldevelopment in connection with MURCS association.

Persistent torticollis, facial asymmetry, grooved tongue, and dolicho-odontoid process in connection with atlas malformation complex in three family subjects.

Congenital clefts and other malformations of the atlas are incidental findings identified while investigating the cervical spine following trauma. A persistent bifid anterior and posterior arch of the atlas beyond the age of 3-4 years is observed in skeletal dysplasias, Goldenhar syndrome, Conradi syndrome, and Down's syndrome. There is a high incidence of both anterior and posterior spina bifida of the atlas in patients with metabolic disorders, such as Morquio's syndrome [Baraitser and Winter in London dysmorphology database, Oxford University Press, 2005; Torriani, Lourenco in Rev Hosp Clin Fac Med Sao Paulo 53: 73-76, 2002]. We report two siblings and their mother, with congenital, persistent torticollis, plagiocephaly, facial asymmetry, grooved tongues, and asymptomatic "dolicho-odontoid process". All are of normal intelligence. No associated Neurological dysfunction, paresis, apnoea, or failures to thrive were encountered. Radiographs of the cervical spine were non-contributory, but 3D CT scanning of this area allowed further visualisation of the cervico-cranial malformation complex in this family and might possibly explain the sudden early juvenile mortality. Agenesis of the posterior arch of the atlas and bifidity/clefting of anterior arch of the atlas associated with asymptomatic "dolicho-odontoid process" were the hallmark in the proband and his female sibling. Some of the features were present in the mother. All the family subjects were investigated. To the best of our knowledge the constellation of malformation complex in this family has not been previously reported.

Craniovertebral malformation complex in a child with Weismann-Netter-Stuhl syndrome.

OBJECTIVE: Bowing of the legs is usually thrown into the basket of vitamin D deficiency rickets; therefore, a significant number of affected children can be misdiagnosed and improperly managed. This case illustrates how the careful clinical and radiological assessment of such a case can lead to the adequate understanding of its etiology. DESCRIPTION: We report a sporadic case of a 2-year-old male child who presented with radiological features that were compatible with Weismann-Netter-Stuhl syndrome. In addition, we observed craniovertebral malformation complex. He was of normal intelligence. To our knowledge, the combination of Weismann-Netter-Stuhl syndrome and presence of a hypoplastic occipitalized atlas and further C2-C3 fusion has not been reported before. The diagnosis of Weismann-Netter-Stuhl is discussed. Classically, Weismann-Netter-Stuhl syndrome is characterized by short stature, mental retardation (in some individuals), dural calcification, and anterior bowing of the tibiae. However, we believe that careful clinical and radiological examinations can reveal more striking data which might positively reflect on the whole process of management. COMMENTS: We postulate that the congenital limitations in neck movements in our patient developed because of the marked fusion of the hypoplastic and occipitalized atlas and simultaneous C2-C3 fusion. Therefore, if this form of malformation is disregarded, there may be involvement of the atlantoaxial structure, and this can possibly lead to serious neurological and even life-threatening complications. The use of CT scanning for the detection of such abnormalities can be remarkably important.

Can Multiple Hereditary Exostoses Overlap With Mesomelic Dysplasia?

BACKGROUND: We studied an unusual combination of severe short stature, mesomelia (Leri-Weill dyschondrosteosis syndrome), and multiple exostosis in several family subjects over three generations. The pattern of inheritance was compatible with autosomal dominant. METHODS: Of 21 affected members over three generations, shortness of stature, associated with mesomelia resembling Leri-Weill dyschondrosteosis syndrome with no exostoses was evident in three family subjects. The rest of the family subjects manifested with normal height, and yet multiple exostoses. In this family, the skeletal manifestations were sufficiently variable for the presentation to be with either short stature or scoliosis, a Madelung' deformity, or with severe hallux valgus associated with exostosis and with Leri-Weill dyschondrosteosis syndrome. RESULTS: Subjects with structural chromosomal aberrations of the proband IV-7, who manifested with normal height but with multiple exostoses were excluded via 20 CAG-banded mitoses (there were no microdeletions or microduplication after performing Array-CGH-analysis). In addition, DNA examination for subject IV-8 (male cousin of the proband showed short stature and Leri-Weill dyschondrosteosis syndrome) revealed no evidence of SHOX deletions. CONCLUSION: We described a multigenerational non-consanguineous North African family , in which mesomelic dysplasia, whose clinical and radiological phenotypes resembled dyschondrosteosis, was a prominent feature in three family subjects. Multiple exostoses were evident in several other family subjects (most were with normal height). We would like to emphasize the variability in the phenotypic expression of multiple exostosis, especially the confusion that might arise when the condition appears both clinically and radiologically to be more complicated, and the overall picture might then be overlapped with one of the other bone dysplasias such as Leri-Weill dyschondrosteosis syndrome.

Broad spectrum of skeletal malformation complex in patients with cleidocranial dysplasia syndrome: radiographic and tomographic study.

PURPOSE: Cleidocranial dysplasia is an autosomal dominant disorder characterized by defective ossification of the intramembraneous ossification (primarily the clavicles, cranium, and pelvis), and it is caused by mutations in the RUNX2 gene that is responsible for osteoblast differentiation. Spine deformities were of progressive nature and considered to be the major orthopedic abnormalities encountered in our practice in patients with cleidocranial dysplasia. We aimed to further delineate the underlying spine pathology and its etiological understanding. Extraspinal deformities were dealt with respectively. MATERIAL AND METHODS: In this paper, we describe 7 patients who were consistent with the phenotypic and the genotypic characterization of cleidocranial dysplasia. Reformatted computed tomography (CT) scans have been applied in several instances to further understand the underlying pathology of progressive spine tilting. Radiographs were sufficient to illustrate other skeletal malformations. RESULTS: Anatomical survey demonstrates that a broad spectrum of frequently unrecognized orthopedic aberrations were encountered. We believe that torticollis has evolved in connection with the persistence of synchondrosis of the skull base and the upper cervical spine and these are strongly correlated to the well-known pathology of posterior occipital synchondrosis. Similarly, scoliosis and kyphoscoliosis resulted from the pathologic aberration of the cartilaginous stage of disrupted embryological development. All our results are discussed for the first time. Coxa vara, patellar dysplasia, and genu valgum were observed as extraspinal deformities. CONCLUSION: This paper includes for the first time the anatomical analysis of the malformation complex of the craniocervical and the entire spine in patients with cleidocranial dysplasia. Reformatted CT scan was the modality of choice. We were able to illustrate that the persistence of skull base and the cervical spine synchondrosis were correlated with the pathological mechanism of the posterior occipital synchondrosis. Therefore, injuries to the craniocervical region in these patients might lead to a wide range of dreadful complications, ranging from complete atlanto-occipital or atlanto-axial dislocation to nondisplaced occipital condyle avulsion fractures with the possibility of morbid and or mortal outcome. On the other hand, the persistence of a cartilaginous spine was the reason behind the progressive spine tilting. This pathological form can be considered as a notoriously unpredictable malformation complex. The value of presenting these patients is to demonsterate that the genotype is not a precise index to assess the severity and the natural history of the phenotype.

Facial dysmorphism associated with distinctive spine abnormalities in a girl and her mother: novel syndromic association.

Facial dysmorphism associated with distinctive spine abnormalities has been encountered in a girl and her mother. A three-dimensional reformatted spinal computed tomography scan showed a combination of distinctive abnormalities such as failure of anterior formation of the vertebral bodies, malsegmentation, and Forestier disease. Mutations were not found in the GDF6 gene. We describe a hitherto undescribed autosomal dominant entity.

Diffuse skull base/cervical fusion syndromes in two siblings with spondylocostal dysostosis syndrome: analysis via three dimensional computed tomography scanning.

STUDY DESIGN: A study on a pair of male sibs to reach for the etiological understanding of unusual skull base/spine maldevelopment. OBJECTIVE: Previously, radiographs alone were used to formulate this diagnosis. Here, three-dimensional computed tomography (3D CT) studies further clarified the typical diagnostic findings associated with spondylocostal dysostosis (SCD). Interestingly, patients with SCD are at increased risk for diffuse skull base/cervical fusion syndromes and can result in severe neurologic deficits associated with any degree of trauma. SUMMARY OF BACKGROUND DATA: Classically SCD is defined as a skeletal dysplasia with clinical and radiologic manifestations, consisting of short neck and trunk, nonprogressive scoliosis and abnormalities of vertebral segmentation and of the ribs. Radiograms have been adopted as the only modality for the classification and prognostication of patients with SCD. METHODS: Detailed clinical and radiographic examinations were undertaken with emphasis on the significance of the 3D CT scanning. RESULTS: We observed extensive fusion of the clivus with the cervical/entire spine, resulting in a remarkable solid, immobile, and fixed bony ankylosis of extremely serious outcome. CONCLUSION: Patients with spondylcostal dysostosis are predisposed to develop extensive skull-base-cervical spine fusion. The latter might lead to the development of a solid, immobile, and fixed bony ankylosis. In children/adults trivial injuries and/or high-energy trauma can lead to serious intracranial and spinal cord injury. Comprehensive orthopedic and neurosurgeons management must follow the recognition of these anomalies. To the best of our knowledge, no previous CT studies of the spine have been published in patients with SCD.

Ischiopubic and odontoid synchondrosis in a boy with progressive pseudorheumatoid chondrodysplasia.

PURPOSE: To present the case of a 14-year-old boy with clinical and radiographic features of pseudorheumatoid chondrodyspalsia with additional, potentially serious, cervical malformations. METHODS: Detailed clinical and radiological examinations were undertaken with emphasis on the usefulness of 3D-CT scanning. RESULTS: There was synchondrosis between the odontoid and the body of the axis and the cephalad part of the odontoid was detached. Bilateral ischiopubic ossification defects and ischiopubic and odontoid synchondroses were additional abnormalities. 3D-CT scan showed an orthotopic type of os odontoideum associated with an occult axial fracture. CONCLUSION: Children who are younger than seven years of age are predisposed to develop odontoid fracture. The latter occur because of the presence of physiological odontoid synchondrosis, but fractures can result from trivial injuries as well as from high-energy trauma. The persistence of an infantile odontoid, with a large pre-adulthood head in children with skeletal dysplasias, is a major risk factor for sudden death or significant morbidity. Comprehensive orthopaedic management must follow early identification of these malformations.

Craniocervical junction malformation in a child with Oromandibular-limb hypogenesis-Möbius syndrome.

We report a male child with Oromandibular-limb hypogenesis (OMLH), the main features being bilateral sixth and seventh nerve palsies, limb anomalies and hypoplasia of the tongue. Additional features were shortness of the neck associated with torticollis. Radiographs of the cervical spine were non-contributory, but 3D computed tomography (CT) scanning of this area identified: a) congenital hypoplasia of the atlas; b) the simultaneous development of occiput-atlas malformation/developmental defect. To our knowledge, this is the first clinical report assessing the cervico-cranium malformation in a child with OMLH-Möbius syndrome.

Atlanto-axial rotatory fixation in a girl with Spondylocarpotarsal synostosis syndrome.

We report a 15-year-old girl who presented with spinal malsegmentation, associated with other skeletal anomalies. The spinal malsegmentation was subsequently discovered to be part of the spondylocarpotarsal synostosis syndrome. In addition, a distinctive craniocervical malformation was identified, which included atlanto-axial rotatory fixation. The clinical and the radiographic findings are described, and we emphasise the importance of computerised tomography to characterize the craniocervical malformation complex. To the best of our knowledge, this is the first clinical report of a child with spondylocarpotarsal synostosis associated with atlanto-axial rotatory fixation.

Progressive congenital torticollis in VATER association syndrome.

STUDY DESIGN: A family study to reach the diagnosis of a multiple malformation syndrome. OBJECTIVE: To determine the cause of torticollis, in a patient with the VATER association. SUMMARY OF BACKGROUND DATA: The VATER association is a combination of vertebral anomalies, anal stenosis, tracheo-esophageal fistula, and radial anomalies. It needs a multidisciplinary approach with a major input from orthopedic surgeons. Torticollis in this condition has not been reported before. METHODS: Detailed family history and radiologic study using plain radiographs and three-dimensional-reconstruction. RESULTS: Bony abnormalities at the base of the skull and upper cervical vertebrae were found. CONCLUSIONS: It is postulated that the bony abnormalities were the underlying cause of the neurologic problem.

Subtotal amelia in a child with autosomal recessive hypohidrotic ectodermal dysplasia.

We report an inbred Tunisian family, in which the proband manifested signs of hypohidrotic ectodermal dysplasia, subtotal amelia, scoliosis and left renal agenesis. Two other family members had the full clinical criteria of hypohidrotic ectodermal dysplasia, characterized by deficient sweat glands, hypodontia, hypoplasia of the mucous glands, and fine hair. Nine family subjects had variable clinical expression of the disorder.