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Cleidocranial dysplasia (CCD) is a rare hereditary disease of unknown etiology which was previously known as cleidocranial dysostosis. It usually follows an autosomal dominant mode of transmission with no predilection of genre or ethnic group. It is caused by a mutation of RUNX2, characterized by generalized dysplasia of the bones and teeth. Affected individuals have short stature, atypical facial features, and skeletal anomalies affecting mainly the skull and clavicle. The dental manifestations are mainly delayed exfoliation of the primary teeth and delayed eruption of the permanent teeth, with multiple impacted supernumeraries, and the absence of cellular cementum. The frequency of this disorder is 1 per million individuals. Here we report a rare case of CCD in a 23 year old female patient having most of the characteristic features of this syndrome. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between prenatal ultrasonography (USG) and fetal autopsy findings. Among 453 pregnancy terminations performed because of fetal anomalies on prenatal USG, 54 with skeletal dysplasia on fetal autopsy were included in this retrospective study. The most common diagnoses among the 54 fetal autopsies were osteogenesis imperfecta (n=12), dysostosis (n=10), achondroplasia (n=9), arthrogryposis (n=6), and thanatophoric dysplasia (n=6). The prenatal USG and fetal autopsy findings showed complete agreement in 35 cases (64.8%), partial agreement in nine cases (16.6%), and disagreement in 10 cases (18.5%). Fetal autopsy via perinatal pathology is essential for precise identification of the type of skeletal dysplasia; it should be routinely performed to confirm the diagnosis of prenatally detected fetal anomalies. Autopsy is vital for accurate prenatal diagnosis and the 'gold standard' technique for the identification of clinically important abnormalities. [ABSTRACT FROM AUTHOR]

The objective of our study is to estimate the frequency and types of the tarsal coalition in the populations of the Czech Lands, where this type of data is still missing. Examined skeletal collections belong to seven different sites and periods (from the Early Bronze Age through the Migration Period and Middle Ages until the 20th century). Tarsal coalition is hereditary abnormal bridging between two tarsal bones (mainly talus, calcaneus, and navicular) which would normally be separate bones. The bridging is caused by a type of connective tissue. Gross macroscopic analysis and comparison with clinical and archaeological literature were used to detect the signs of tarsal coalition. In some cases, the analysis was combined with the radiographic examination. A total of 267 individuals from the following locations were observed: Mikulovice, Kolín, Praha-Zličín, Sady-Špitálky, Trutmanice, Znojmo, and skeletons of recent cadavers from the Department of Anatomy, Faculty of Medicine, Masaryk University, Brno. Another 212 isolated tarsal bones from Brno ossuary material (dated to the 13th-18th century and currently deposited in the Department of Anatomy) were also studied. We estimated that the frequency of tarsal coalition (when individuals from all seven studied archaeological collections were pooled) was 5.6 %. The tarsal coalition frequencies for individual collections ranged between 2.3 % - 10.3 %. If the ossuary material was included in the total tarsal coalition frequency calculations (the number of individuals from the ossuary material was calculated as the minimum number of individuals), the tarsal coalition frequency was 6.1 %. In most of the cases, the calcaneonavicular coalition was detected. The findings may expand our overall understanding of tarsal coalition and stimulate further clinical research when looking for a causal link between tarsal coalition and orthopaedic diseases, such as painful, rigid flatfoot (fibular spastic flatfoot, tarsal synostosis, or dysostosis), and their possible secondary complications (intra-articular trauma, infection, arthropathy, osteonecrosis, neoplasm). [ABSTRACT FROM AUTHOR]

Skeletal dysplasia encompasses a heterogeneous group of over 400 genetic disorders. They are individually rare, but collectively rather common with an approximate incidence of 1/5000. Thus, radiologists occasionally encounter skeletal dysplasias in their daily practices, and the topic is commonly brought up in radiology board examinations across the world. However, many radiologists and trainees struggle with this issue because of the lack of proper resources. The radiological diagnosis of skeletal dysplasias primarily rests on pattern recognition—a method that is often called the "Aunt Minnie" approach. Most skeletal dysplasias have an identifiable pattern of skeletal changes composed of unique findings and even pathognomonic findings. Thus, skeletal dysplasias are the best example to which the Aunt Minnie approach is readily applicable. [ABSTRACT FROM AUTHOR]

In 2019, the Nosology Committee of the International Skeletal Dysplasia Society provided an updated version of the Nosology and Classification of Genetic Skeletal Disorders. This is a reference list of recognized diseases in humans and their causal genes published to help clinician diagnosis and scientific research advances. Complementary to mammalian models, zebrafish has emerged as an interesting species to evaluate chemical treatments against these human skeletal disorders. Due to its versatility and the low cost of experiments, more than 80 models are currently available. In this article, we review the state-of-art of this "aquarium to bedside" approach describing the models according to the list provided by the Nosology Committee. With this, we intend to stimulate research in the appropriate direction to efficiently meet the actual needs of clinicians under the scope of the Nosology Committee. [ABSTRACT FROM AUTHOR]

Background: Acrodysostosis is a rare hereditary disorder described as a primary bone dysplasia with or without hormonal resistance. Pathogenic variants in the PRKAR1A and PDE4D genes are known genetic causes of this condition. The latter gene variants are more frequently identified in patients with midfacial and nasal hypoplasia and neurological involvement. The aim of our study was to analyse and confirm a genetic cause of acrodysostosis in a male patient. Case presentation: We report on a 29-year-old Lithuanian man diagnosed with acrodysostosis type 2. The characteristic phenotype includes specific skeletal abnormalities, facial dysostosis, mild intellectual disability and metabolic syndrome. Using patient's DNA extracted from peripheral blood sample, the novel, likely pathogenic, heterozygous de novo variant NM_001104631.2:c.581G > C was identified in the gene PDE4D via Sanger sequencing. This variant causes amino acid change (NP_001098101.1:p.(Arg194Pro)) in the functionally relevant upstream conserved region 1 domain of PDE4D. Conclusions: This report further expands the knowledge of the consequences of missense variants in PDE4D that affect the upstream conserved region 1 regulatory domain and indicates that pathogenic variants of the gene PDE4D play an important role in the pathogenesis mechanism of acrodysostosis type 2 without significant hormonal resistance. [ABSTRACT FROM AUTHOR]

The musculoskeletal (MSK) system begins to form in the third week of intrauterine development. Multiple genes are involved in the complex different processes to form the skeleton, muscles and joints. The embryonic period, from the third to the eighth week of development, is critical for normal development and therefore the time when most structural defects are induced. Many of these defects have a genetic origin, but environmental factors may also play a very important role. This review summarizes the embryology of the different components of the MSK system and their configuration as an organ-system, analyzes the clinical implications resulting from failures in the process of organogenesis, and describes the first approach to diagnosis of skeletal abnormalities using prenatal ultrasound. [ABSTRACT FROM AUTHOR]

A removable partial denture supported by resin-bonded precision attachments was constructed for a patient with intra oral symptoms of a cleidocranial dysostosis. Because of the anatomic situation, the youth, and the preprosthetic orthodontic treatment of the patient, a conventional prosthetic solution seemed inappropriate. Custom-made attachments were constructed with the spark erosion technique. They were fixed to the abutment teeth with resin-bonded retainers. The combination of the resin-bonding technique with the modern technology of spark erosion thus allowed a conservative approach to the oral rehabilitation of a young patient. [ABSTRACT FROM AUTHOR]

The article focuses on research regarding accessory jaw structures and teeth abnormalities. In cleidocranial dysostosis and cleft lip, incidence of multiple supernumerary teeth was found. Sporadic manifestations of supernumeraries occur mostly in the midline and molar regions of the maxilla, followed by the premolar region of the mandible. Researchers have concluded that double teeth result from either germination or fusion. Several individuals have been found to have both unilateral and bilateral hyperplasia and benign neoplasia of the coronoid process of the mandible.

The article focuses on the clinical and genetic considerations in craniofacial malformations. It is stated that oral manifestations of disorders of genetic origin can be illustrated in marked tissue changes of the craniofacial complex. It is believed that appropriate evaluation of the altered pattern of dental formation or dental appearance as well as tooth eruption irregularities may prove to be helpful in the diagnosis of an underlying genetic condition. Several researches have been conducted on the postnatal changes of the craniofacial complex in patients with various diseases of genetic origin, but it is stated that more information is required for better prognosis and treatment planning.

The article discusses the genetic factors that contribute to the development of occlusion. It cites that systemic conditions influence the development of the dentition and occlusion such as mandibular facial dysostosis, marfan syndrome, down syndrome, and anhydrotic ectodermal dysplasia. It cites that amelogenesis imperfecta, an autosomal dominant inherited hypocalcification of enamel, contributes to the heritable defects of enamel and dentin. Moreover, it mentions that the shovel shape of incisors may be due to genetic factors.

The mucopolysaccharidoses are a heterogeneous group of inherited lysosomal storage disorders, characterized by the accumulation of undegraded glycosaminoglycans in various organs, leading to tissue damage. Mucopolysaccharidoses include eight individual disorders (IS [Scheie syndrome], IH [Hurler syndrome], II, III, IV, VI, VII and IX). They have autosomal-recessive transmission with the exception of mucopolysaccharidosis II, which is X-linked. Each individual disorder has a wide spectrum of phenotypic variation, depending on the specific mutation, from very mild to very severe. The skeletal and central nervous systems are particularly affected. The typical clinical presentation includes organomegaly, dysostosis multiplex with short trunk dwarfism, mental retardation and developmental delay. In this article, we review the neuroimaging manifestations of the different types of mucopolysaccharidoses including the dysostosis multiplex of the skull and spine as well as the various central nervous system complications. These include white matter injury, enlargement of the perivascular spaces, hydrocephalus, brain atrophy, characteristic enlargement of the subarachnoid spaces as well as compressive myelopathy. The correlation between several of the neuroimaging features and disease severity remains controversial, without well-established imaging biomarkers at this time. Imaging has, however, a crucial role in monitoring disease progression, in particular craniocervical junction stenosis, cord compression and hydrocephalus, because this allows for timely intervention before permanent damage occurs. [ABSTRACT FROM AUTHOR]

Introduction. Patients with spondylocostal dysostosis (SCD) have congenital spine and rib deformities associated with frequently severe thoracic insufficiency and respiratory compromise. The literature is largely composed of case reports and small cohorts, and there is little information regarding adults with this condition. In this report, we describe the natural history of a conservatively treated patient and include quality-of-life issues such as childbearing, athletic participation, and occupational selection. Case Presentation. We present a patient with SCD who was conservatively treated by a single physician from birth for 31 years. Our patient was capable of a reasonably good quality of life through adulthood, including participation in gymnastics and employment. At age 18, she became pregnant and subsequently terminated the pregnancy due to obstetrical concerns for compromised respiration. She has had intermittent respiratory complaints and occasionally experiences dyspnea with exertion, but this only has limited her during certain activities in the past three years. Currently, she takes naproxen for chronic back pain with periodic exacerbations. Discussion. Other cases in the literature have described adult SCD patients who have received nonoperative treatment and achieved a wide range of functional outcomes. This provides some limited evidence to suggest that select patients with SCD may be treated conservatively and achieve a reasonable quality of life. However, close clinical follow-up with these patients is recommended, particularly early on, considering the high rates of infant morbidity and mortality. Chest physiotherapy and early pulmonary care have been associated with favorable outcomes in infancy. Surgery to increase thoracic volume and correct scoliosis has been shown in some cases to improve respiratory function. Treatment depends on the degree of thoracic insufficiency and quality of life. The natural history of SCD remains largely unknown, but some patients are capable of relatively favorable life spans, employment, and participation in athletics. [ABSTRACT FROM AUTHOR]

Aim: Mucopolysaccharidosis Type IVA (MPS IVA), Morquio A, is caused by the deficiency in lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase. Multisystemic involvements include skeletal systems, pulmonary disease, valvular heart disease, hearing loss, mild hepatomegaly, corneal clouding, coarse facial features. Materials and Methods: We retrospectively analyzed clinical and laboratory and follow up findings of our 25 patients with ministry for primary industries independent verification agency. Results: Mean age of the patients was 14.9±7.05 (5.5-36 years). Mean age at diagnosis was 7.3±6.2 years (6 months-31 years). Female: male ratio was 13/12. All patients had skeletal manifestation and X-ray analysis demonstrated "dysostosis multiplex". Twelve patients (48%) had cardiac valve disease. Twenty three (92%) patients had corneal clouding, 15 (60%) patients had hearing loss and 9 (36%) had hepatomegaly. Six (24%) patients were unable to walk. Mean follow up period is 7.4 years ±3.5 years (3 months-17 years). Four patients have not visit our clinical for last =3 years. Three patients died during follow up. Conclusion: MPS IVA is a severe disorder and is usually fatal in the second or third decade of life due to the complications of the disease. Early diagnosis of the patient became more important, because specific therapy with elasulphase alpha was approved recent years ago. [ABSTRACT FROM AUTHOR]

Proximal 16p11.2 microdeletions are recurrent microdeletions with an overall prevalence of 0.03%. In patients with segmentation defects of the vertebra ( SDV), a burden of this microdeletion was observed with TBX6 as a candidate gene for SDV. In a published cohort of patients with congenital scoliosis ( CS), TBX6 haploinsufficiency was compound heterozygous with a common haplotype. Besides, a single three-generation family with spondylocostal dysostosis ( SCD) was reported with a heterozygous stop-loss of TBX6. These observations questioned both on the inheritance mode and on the variable expressivity associated with TBX6-associated SDV. Based on a national recruitment of 56 patients with SDV, we describe four patients with variable SDV ranging from CS to SCD associated with biallelic variations of TBX6. Two patients with CS were carrying a proximal 16p11.2 microdeletion associated with the previously reported haplotype. One patient with extensive SDV was carrying a proximal 16p11.2 microdeletion associated with a TBX6 rare missense change. One patient with a clinical diagnosis of SCD was compound heterozygous for two TBX6 rare missense changes. The three rare variants were affecting the chromatin-binding domain. Our data illustrate the variable expressivity of recessive TBX6 ranging from CS to SCD. [ABSTRACT FROM AUTHOR]

Ischiospinal Dysostosis (ISD) is a complex and very rare medical entity. It is associated with kyphoscoliosis, dysplasia or aplasia of the ischial rami, segmental anomalies of the bony vertebrae, and peculiar facial morphologies. In this case report, we present a child with Ischiospinal Dysostosis and Pierre-Robin Syndrome. This case report is unique as we followed the patient for 13 years in which he had multiple spinal procedures to treat his kyphoscoliosis. In this paper, we elucidated the number of case reports with documented follow-up regarding spinal cord injury or other complications of ISD and its management. [ABSTRACT FROM AUTHOR]

The article offers information on the Treacher Collins syndrome (TCS), a rare craniofacial morphogenesis that affect one in every 50,000 live births in Great Britain and the U.S. The topics discussed include the etiology and genetics of TCS, the different kinds of TCS, and the clinical manifestations of TCS.

The acrofacial dysostoses (AFD) are a genetically heterogeneous group of inherited disorders with craniofacial and limb abnormalities. Rodriguez syndrome is a severe, usually perinatal lethal AFD, characterized by severe retrognathia, oligodactyly and lower limb abnormalities. Rodriguez syndrome has been proposed to be a severe form of Nager syndrome, a non-lethal AFD that results from mutations in SF3B4, a component of the U2 small nuclear ribonucleoprotein particle (U2 snRNP). Furthermore, a case with a phenotype intermediate between Rodriguez and Nager syndromes has been shown to have an SF3B4 mutation. We identified heterozygosity for SF3B4 mutations in Rodriguez syndrome, confirming that the phenotype is a dominant disorder that is allelic with Nager syndrome. The mutations led to reduced SF3B4 synthesis and defects in mRNA splicing, primarily exon skipping. The mutations also led to reduced expression in growth plate chondrocytes of target genes, including the DLX5, DLX6, SOX9, and SOX6 transcription factor genes, which are known to be important for skeletal development. These data provide mechanistic insight toward understanding how SF3B4 mutations lead to the skeletal abnormalities observed in the acrofacial dysostoses. [ABSTRACT FROM AUTHOR]

Sialidoses are autosomal recessive disorders caused by NEU1 gene mutations and are classified on the basis of their phenotype and onset age. Sialidosis type II, with infantile onset, has a more severe phenotype characterized by coarse facial features, hepatomegaly, dysostosis multiplex, and developmental delay while patients with the late and milder type, known as 'cherry red spot-myoclonus syndrome' develop myoclonic epilepsy, visual impairment and ataxia in the second or third decade of life. The diagnosis is usually suggested by increased urinary bound sialic acid excretion. We recently described genetically diagnosed patients with a specially mild phenotype, no retinal abnormalities and normal urinary sialic acid. This observation suggests that genetic analysis or the demonstration of the neuraminidase enzyme deficiency in cultured fibroblasts are needed to detect and diagnose mildest phenotypes. [ABSTRACT FROM AUTHOR]

Acromelic frontonasal dysostosis ( AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling. [ABSTRACT FROM AUTHOR]

Spondylocostal dysostosis (SCD) is a rare anomaly of axial skeleton due to flawed embryological development characterized by malformed ribs, fused ribs, and hemivertebra. Case one: A newborn baby boy with right-sided polythelia, meningocele, fan-like configuration of 3rd and 4th rib, fused 5th and 6th rib, and 3rd thoracic hemivertebra was delivered to a second gravid mother by elective cesarean section. Based on clinical examination and radiological picture, a diagnosis of SCD with meningocele with right-sided polythelia was made. Case two: Baby girl born to primigravida mother by cesarean section had hemivertebrae with multiple right-sided rib defects, short neck, preauricular ear tags, imperforate anus, and rectovaginal fistula. Very few cases of SCD have been reported in literature with neural tube defects (NTDs) with supernumerary nipple, none from developing country. Till now, there is limited literature regarding the associations of SCD none showing its association with the genitourinary system without NTDs. We need to study the causal associations of SCD with detailed genetic work up as it is not so uncommon as presumed. [ABSTRACT FROM AUTHOR]

Ellis-van Creveld syndrome (EvC) is a rare autosomal recessive disorder characterized by disproportionate chondrodysplasia, postaxial polydactyly, nail dystrophy, dental abnormalities and in a proportion of patients, congenital cardiac malformations. Weyers acrofacial dysostosis (Weyers) is another dominantly inherited disorder allelic to EvC syndrome but with milder phenotypes. Both disorders can result from loss-of-function mutations in either EVC or EVC2 gene, and phenotypes associated with the two gene mutations are clinically indistinguishable. We present here a clinical and molecular analysis of a Chinese family manifested specific features of EvC syndrome. Sequencing of both EVC and EVC2 identified two novel heterozygous splice site mutations c.384+5G>C in intron 3 and c.1465-1G>A in intron 10 in EVC, which were inherited from mother and father, respectively. In vitro minigene expression assay, RT-PCR and sequencing analysis demonstrated that c.384+5G>C mutation abolished normal splice site and created a new cryptic acceptor site within exon 4, whereas c.1465-1G>A mutation affected consensus splice junction site and resulted in full exon 11 skipping. These two aberrant pre-mRNA splicing processes both produced in-frame abnormal transcripts that possibly led to abolishment of important functional domains. To our knowledge, this is the first report of EVC mutations that cause EvC syndrome in Chinese population. Our data revealed that EVC splice site mutations altered splicing pattern and helped elucidate the pathogenesis of EvC syndrome. [ABSTRACT FROM AUTHOR]

In 1981, Casamassima and colleagues described an autosomal recessive syndrome of spondylocostal dysostosis associated with anal and urogenital anomalies. Here, I describe 1 new fetus who presented with limb-body wall defect as a novel association, compile 7 patients, and review the clinical phenotype of Casamassima-Morton- Nance syndrome. This appears to be the 1 st Casamassima- Morton-Nance syndrome fetus with this complex malformation. In light of this manifestation, a detailed comparative phenotypic analysis of published patients revealed a heterogeneous syndrome with significant clinical variability. Accordingly, it is proposed that Casamassima-Morton-Nance syndrome should be considered in those patients with the combination of a short and asymmetric thorax with rib and vertebral anomalies and scoliosis (spondylocostal-like pattern), anal atresia, absent external genitalia, renal and urethral abnormalities (caudal dysgenesis complex), craniofacial dysmorphic features (mainly flat nose with anteverted nares, low-set/ abnormal ears, and short neck), hydrops, oligohydramnios, and a poor clinical outcome. [ABSTRACT FROM AUTHOR]

Ischiospinal dysostosis (ISD) is a polytopic dysostosis characterized by ischial hypoplasia, multiple segmental anomalies of the cervicothoracic spine, hypoplasia of the lumbrosacral spine and occasionally associated with nephroblastomatosis. ISD is similar to, but milder than the lethal/semilethal condition termed diaphanospondylodysostosis (DSD), which is associated with homozygous or compound heterozygous mutations of bone morphogenetic protein-binding endothelial regulator protein (BMPER) gene. Here we report for the first time biallelic BMPER mutations in two patients with ISD, neither of whom had renal abnormalities. Our data supports and further extends the phenotypic variability of BMPER-related skeletal disorders. [ABSTRACT FROM AUTHOR]

Morquio disease (MPS IV) is an autosomal recessive disease caused by deficiency of N-acetyl galactosamine-6-sulfatase (MPS IV A) or, of β-galactosidase (MPS IV B). The key symptoms found in patients with MPS IV A include musculoskeletal abnormalities and limited growth. Musculoskeletal abnormalities include pectus carinatum, genu valgum, kyphosis, atlanto-axial subluxation and joint laxity. Typical clinical findings and radiological picture provides clue for diagnosis of Morquio's disease. Urinary mucopolysccharides assay is the screening test for diagnosis while this can be confirmed by enzymatic and molecular study. Bicuspid aortic valve is a rare finding in Morquio disease. [ABSTRACT FROM AUTHOR]

Expert radiology opinions are often requested to aid diagnosis of skeletal dysplasias or dysostoses, but due to variability in the imaging protocols used at different centres the views presented may be considered inadequate or incomplete resulting in diagnostic delays and increased patient and family anxiety. We propose the introduction of a standardised protocol that may be adapted in certain specific situations. [ABSTRACT FROM AUTHOR]

Nager syndrome is a rare syndrome resulting from developmental abnormalities of the first and second branchial arches. Nager syndrome is rare and mostly sporadic. The main clinical features consist of craniofacial, limb, and musculoskeletal morphogenesis. These findings included malar hypoplasia, maxillomandibular hypoplasia, micrognathia, downslanting palpebral fissures, cleft palate, ear anomalies, hypoplastic thumb, short forearm, proximal radioulnar synostosis, atrial septal defect, lower limb deformities, and flat nasal bridge. The prevalence is unknown; about 100 cases of Nager syndrome have been published up to now. Patients with Nager syndrome are found worldwide among all racial and ethnic groups. Trismus and glossoptosis resulting in oropharyngeal airway narrowing cause life-threatening respiratory distress for patients with Nager syndrome. In this case report, dental rehabilitation of a 10-year-old child with Nager syndrome is presented. [ABSTRACT FROM AUTHOR]

Skeletal dysplasias (SDs) constitute a group of heterogeneous disorders affecting growth morphology of the chondro-osseous tissues. Prenatal diagnosis of SD is a considerable clinical challenge due to phenotypic variability. We performed a retrospective analysis of the fetal autopsies series conducted between January 2006 and December 2012 at our center. SD was detected in 54 (10%) out of 542 fetal autopsy cases which included; 11.1% thanatophoric dysplasia (n= 6), 7.4% achondroplasia (n= 4), 3.7% osteogenesis imperfect (n= 2), 1.9% Jarcho-Levin Syndrome (n= 1), 1.9% arthrogryposis (n= 1), 1.9% Dyggve-Melchior-Clausen syndrome (n= 1), 72.1% of dysostosis cases (n= 39). All SD cases were diagnosed by ultrasonography. In 20 of the cases, amniocentesis was performed, 4 cases underwent molecular genetic analyses. Antenatal identification of dysplasia is important in the management of pregnancy and in genetic counseling. Our data analysis showed that SD is usually detected clinically after the 20th gestational week. Genetic analyses for SD may provide early diagnosis and management. [ABSTRACT FROM PUBLISHER]

Cleidocranial dysplasia (CCD) is a rare autosomal dominant condition with generalized dysplasia of bone characterized by delayed closure of cranial sutures, hypoplastic or aplastic clavicles, short stature, dental abnormalities and a variety of other skeletal abnormalities. We report two cases presenting with classical features of CCD because of its rarity. [ABSTRACT FROM AUTHOR]

Pycnodysostosis is a rare autosomal recessive disease due to a mutation in the gene for the enzyme Cathepsin K. It is characterized by short stature, craniofacial dysmorphias, osteosclerosis, and brittle bones. There are only a few reports in the literature describing surgical interventions for long bone fractures in pycnodysostosis patients, most of which describe intramedullary nail treatment of isolated long bone fractures. We describe a case in which a pregnant female with pycnodysostosis presented with a shaft fracture of the left femur following minor trauma and a history of increasing thigh pain. Radiographs obtained in the emergency room also revealed an impending subtrochanteric fracture of the contralateral side. The acute left femoral shaft fracture was treated with an adolescent-sized intramedullary nail; it was decided to defer surgery on the contralateral side until after pregnancy. Three months later, the patient had the contralateral femur prophylactically fixated with a plate and screws. One year after the index surgery, both methods demonstrated satisfactory healing both clinically and radiographically. Although we recommend use of an intramedullary nail for long bone fractures in patients with pycnodysostosis, a plate can be utilized if health conditions or skeletal morphology precludes use of a nail. [ABSTRACT FROM AUTHOR]

Pycnodysostosis is a rare sclerosing bone disorder characterized by short stature, brachycephaly, short/stubby fingers, open cranial sutures/fontanelle, and diffuse osteosclerosis, where multiple fractures of long bones and osteomyelitis of the jaw are common complications. We present a rare case of pycnodysostosis with chronic suppurative osteomyelitis of the mandible in a 36-year-old woman; which was nonsurgically managed by a conservative approach involving a novel protocol referred to as intra-lesional antibiotic therapy. [ABSTRACT FROM AUTHOR]

Copyright of Acta Pediatrica de Mexico is the property of Instituto Nacional de Pediatria (INP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We report on an adult male with normal intelligence who exhibited an unusual combination of microcephaly, dysostoses of limbs, vertebrae, patellae, and pubic bone, camptodactyly of all fingers, and syndactyly of toes, absent nails on thumbs and some fingers, bilateral cataract, cryptorchidism, polythelia, and nipple-like skin pigmentations of shoulders and upper back. We have been unable to find a description of a similar combination of manifestations in literature. The cause of the anomalies remains unknown. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Istanbul University Faculty of Dentistry / Istanbul Üniversitesi Dis Hekimligi Fakültesi Dergisi is the property of Istanbul University, Faculty of Dentistry and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Jarcho-Levin syndrome represents a spectrum of clinical and radiographic irregularities including abnormal vertebral segmentation or formation defects, rib deformities, and short-trunk dwarfism. These abnormalities cause reduced thoracic capacity for lung development, resulting in thoracic insufficiency syndrome. In the present study, we reviewed outcome measures related to scoliotic curve correction, thoracic growth, and respiratory function following VEPTR treatment in patients with Jarcho-Levin syndrome. Methods: Twenty-nine patients with Jarcho-Levin syndrome, subclassified as spondylocostal dysostosis (SCD) or spondylothoracic dysplasia (STD), were treated with VEPTR expansion thoracoplasty and followed for at least two years since the initial implantation. Spinal and respiratory measures were collected prior to the initial VEPTR implantation, immediately after implantation, and at the most recent follow-up. Results: VEPTR treatment was associated with improved clinical respiratory function and with increases in thoracic height (by 50% in the SCD group and 42% in the STD group) and thoracic width (by 37% in the SCD group and 28% in the STD group). VEPTR treatment resulted in scoliosis curve correction (improvement in the Cobb angle of 41% [22] in the SCD group and 26% [3.7] in the STD group) and in improved thoracic symmetry in patients with SCD. Patients with SCD displayed increased lumbar lordosis, and both groups of patients developed increased thoracic kyphosis approaching normal. Conclusions: VEPTR treatment improved thoracic symmetry, controlled spinal deformity, and was associated with improved clinical respiratory function. [ABSTRACT FROM AUTHOR]

Nager syndrome belongs to the group of acrofacial dysostosis, which are characterized by the association of craniofacial and limb malformations. Recently, exome sequencing studies identified the SF3B4 gene as the cause of this condition in most patients. SF3B4 encodes a highly conserved protein implicated in mRNA splicing and bone morphogenic protein ( BMP) signaling. We performed SF3B4 sequencing in 14 families (18 patients) whose features were suggestive of Nager syndrome and found nine mutations predicted to result in loss-of-function. SF3B4 is the major gene responsible for autosomal dominant Nager syndrome. All mutations reported predict null alleles, therefore precluding genotype-phenotype correlations. Most mutation-negative patients were phenotypically indistinguishable from patients with mutations, suggesting genetic heterogeneity. [ABSTRACT FROM AUTHOR]

Whole-exome sequencing ( WES) has proven its utility in finding novel genes associated with rare conditions and its usefulness is being further demonstrated in expanding the phenotypes of well known diseases. We present here a family with a previously undiagnosed X-linked condition characterized by progressive restriction of joint range of motion, prominence of the supraorbital ridge, audiology issues and hernias. They had an average stature, normal occipitofrontal circumference and intelligence, absence of dysostosis multiplex and otherwise good health. A diagnosis of Hunter syndrome was determined using WES and further supported by biochemical investigations. The phenotype of this family does not correspond to either the severe or attenuated clinical subtypes of Hunter syndrome. As further atypical families are reported, this classification will need to be modified. Our findings highlight the utility of WES in expanding the recognized phenotypic spectrum of known syndromes. [ABSTRACT FROM AUTHOR]

PURPOSE: Skeletal disease causes significant morbidity in mucopolysaccharidoses (MPS), and bone remodeling processes in MPS have not been well characterized. The objective of this study was to determine if biomarkers of bone turnover are abnormal in children with specific MPS disorders (i.e. MSP-I, MPS-II, and MPS-VI) compared to healthy children. METHODS: A cross-sectional study was performed of serum biomarkers of bone formation (bone-specific alkaline phosphatase [BSAP], osteocalcin) and urine biomarkers of bone resorption (pyridinoline, deoxypyridinoline) in MPS and healthy controls. Measures of physical function and pain were obtained using the Children's Health Questionnaire (CHQ). RESULTS: The cohort consisted of 39 children with MPS (MPS-I=26; MPS-II=11; MPS-VI=4) and 51 healthy children. Adjusting for sex and Tanner stage group, MPS individuals had statistically significant increases for osteocalcin (p< 0.001), with trends toward higher BSAP (p=0.054) and urinary pyridinoline (p=0.084). These biomarkers were not significantly associated with CHQ bodily pain and physical-function scores. CONCLUSION: Osteocalcin was increased in children with MPS disorders, with trends for increases in BSAP and urinary pyridinoline, suggesting that bone remodeling is altered in children with MPS. Future studies to assess the ability of these biomarkers to quantify and monitor MPS skeletal disease in response to therapy are needed. [ABSTRACT FROM AUTHOR]

In this review, we discuss aspects of the prenatal diagnosis of fetal skeletal malformations, concentrating on the advantages offered by different imaging techniques and the approaches that are of value in evaluating a suspected skeletal dysplasia. We also briefly address the findings in some of the commoner malformations of the fetal skeleton that may be encountered. [ABSTRACT FROM AUTHOR]

Background To characterize cathepsin K (CTSK) mutations in a group of patients with pycnodysostosis, who presented with either short stature or atypical fractures to pediatric endocrinology or dysmorphic features to pediatric genetics clinics. Methods Seven exons and exon/intron boundaries of CTSK gene for the children and their families were amplified with PCR and sequenced. Sixteen patients from 14 families with pycnodysostosis, presenting with typical dysmorphic features, short stature, frequent fractures and osteosclerosis, were included in the study. Results We identified five missense mutations (M1I, I249T, L7P, D80Y and D169N), one nonsense mutation (R312X) and one 301 bp insertion in intron 7, which is revealed as Alu sequence; among them, only L7P and I249 were described previously. The mutations were homozygous in all cases, and the families mostly originated from the region where consanguineous marriage rate is the highest. Patients with M1I mutation had fractures, at younger ages than the other pycnodysostosis cases in our cohort which were most probably related to the severity of mutation, since M1I initiates the translation, and mutation might lead to the complete absence of the protein. The typical finding of pycnodysostosis and acroosteolysis could not be detected in two patients, although other patients carrying the same mutations had acroosteolysis. Additionally, none of the previously described hot spot mutations were seen in our cohort; indeed, L7P and R312X were the most frequently detected mutations. Conclusions We described a large cohort of pycnodysostosis patients with genetic and phenotypic features, and, first Alu sequence insertion in pycnodysostosis. [ABSTRACT FROM AUTHOR]

During the summer of 2013 seven Italian Tyrolean Grey calves were born with abnormally short limbs. Detailed clinical and pathological examination revealed similarities to chondrodysplastic dwarfism. Pedigree analysis showed a common founder, assuming autosomal monogenic recessive transmission of the defective allele. A positional cloning approach combining genome wide association and homozygosity mapping identified a single 1.6 Mb genomic region on BTA 6 that was associated with the disease. Whole genome re-sequencing of an affected calf revealed a single candidate causal mutation in the Ellis van Creveld syndrome 2 (EVC2) gene. This gene is known to be associated with chondrodysplastic dwarfism in Japanese Brown cattle, and dwarfism, abnormal nails and teeth, and dysostosis in humans with Ellis-van Creveld syndrome. Sanger sequencing confirmed the presence of a 2 bp deletion in exon 19 (c.2993_2994ACdel) that led to a premature stop codon in the coding sequence of bovine EVC2, and was concordant with the recessive pattern of inheritance in affected and carrier animals. This loss of function mutation confirms the important role of EVC2 in bone development. Genetic testing can now be used to eliminate this form of chondrodysplastic dwarfism from Tyrolean Grey cattle. [ABSTRACT FROM AUTHOR]