ABSTRACT
Background and purpose - Motorized intramedullary lengthening nails (ILNs) have been developed as an alternative to external fixators for long bone lengthening. The antegrade approach represents the standard method for tibial ILN insertion. In patients with preexisting ankle and hindfoot fusion a retrograde approach provides an alternative technique that has not been evaluated so far. We report the outcome of this method in 10 patients. Patients and methods - This retrospective study included 10 patients (mean age 18 years [13-25]) with preexisting ankle and hindfoot fusion who underwent tibial lengthening with a retrograde ILN (PRECICE). The mean leg length discrepancy (LLD) was 58 mm (36-80). The underlying conditions were congenital (n = 9) and post tumor resection (n = 1). The main outcome measures were: ILN reliability, distraction achieved, distraction index (DIX), time to bone healing, consolidation index (CIX), complications, and functional results. Results - All patients achieved the goal of lengthening (mean 48 mm [26-80]). Average DIX was 0.6 mm/day (0.5-0.7) and mean CIX was 44 days/cm (26-60). Delayed consolidation occurred in 2 patients and healed after ILN dynamization or nail exchange with grafting. Toe contractures in 2 other patients were resolved with physiotherapy or tenotomy. Until last follow-up (mean 18 months [12-30]) no true complications were encountered, knee motion remained unaffected, and full osseous consolidation occurred in all patients. Interpretation - In patients with LLD and preexisting ankle and hindfoot fusion distal tibial lengthening using a retrograde ILN is a reliable alternative to the standard approach with equivalent bone healing potential and low complication rates leaving the knee unaffected.
Subject(s)
Arthrodesis , Bone Lengthening , Fracture Fixation, Intramedullary , Leg Length Inequality , Postoperative Complications/surgery , Tibia/surgery , Adolescent , Ankle Joint/pathology , Ankle Joint/surgery , Arthrodesis/adverse effects , Arthrodesis/methods , Bone Diseases/congenital , Bone Diseases/surgery , Bone Lengthening/adverse effects , Bone Lengthening/instrumentation , Bone Lengthening/methods , Bone Neoplasms/surgery , Female , Fracture Fixation, Intramedullary/instrumentation , Fracture Fixation, Intramedullary/methods , Germany , Humans , Leg Length Inequality/etiology , Leg Length Inequality/surgery , Magnets , Male , Outcome and Process Assessment, Health Care , Plastic Surgery Procedures/methods , Young AdultABSTRACT
PURPOSE OF REVIEW: We present the reader with insight on the most common disorders of the knee in newborns and infants. Knee issues in this population may confuse the first contact physicians due to certain peculiarities of the immature immune system, small size and underdevelopment of joint anatomy. Data presented here are recent and significant, and something to bear in mind when caring for children of this age. RECENT FINDINGS: With the advent of new diagnostic methods, a shift in the causative agent of pediatric knee infections has been noted. Minimally invasive methods such as arthrocentesis and arthroscopy are successfully employed in treatment of knee problems in newborns and infants. A trial of conservative therapy in congenital patellar instability can give good results, and obviate the need for surgery in some cases. Various syndromes that affect the knee have specific characteristics that need to be recognized early to avoid problems in the future. SUMMARY: Although rare, knee problems in infants can and do occur. Their cause varies significantly and good outcomes require a multidisciplinary approach. Early diagnosis, referral and initiation of treatment protocols can significantly influence the fate of the joint and with it the patients' functional status for life.
Subject(s)
Bone Diseases/diagnosis , Bone Diseases/therapy , Joint Diseases/diagnosis , Joint Diseases/therapy , Knee Joint , Bone Diseases/congenital , Child , Humans , Infant , Infant, Newborn , Joint Diseases/congenital , Knee/abnormalities , Knee Joint/abnormalities , Knee Joint/diagnostic imaging , Knee Joint/surgery , Meniscus/abnormalities , Musculoskeletal Abnormalities/diagnosis , Musculoskeletal Abnormalities/therapyABSTRACT
The term linkeropathies (LKs) refers to a group of rare heritable connective tissue disorders, characterized by a variable degree of short stature, skeletal dysplasia, joint laxity, cutaneous anomalies, dysmorphism, heart malformation, and developmental delay. The LK genes encode for enzymes that add glycosaminoglycan chains onto proteoglycans via a common tetrasaccharide linker region. Biallelic variants in XYLT1 and XYLT2, encoding xylosyltransferases, are associated with Desbuquois dysplasia type 2 and spondylo-ocular syndrome, respectively. Defects in B4GALT7 and B3GALT6, encoding galactosyltransferases, lead to spondylodysplastic Ehlers-Danlos syndrome (spEDS). Mutations in B3GAT3, encoding a glucuronyltransferase, were described in 25 patients from 12 families with variable phenotypes resembling Larsen, Antley-Bixler, Shprintzen-Goldberg, and Geroderma osteodysplastica syndromes. Herein, we report on a 13-year-old girl with a clinical presentation suggestive of spEDS, according to the 2017 EDS nosology, in whom compound heterozygosity for two B3GAT3 likely pathogenic variants was identified. We review the spectrum of B3GAT3-related disorders and provide a comparison of all LK patients reported up to now, highlighting that LKs are a phenotypic continuum bridging EDS and skeletal disorders, hence offering future nosologic perspectives.
Subject(s)
Antley-Bixler Syndrome Phenotype/genetics , Arachnodactyly/genetics , Bone Diseases/congenital , Craniosynostoses/genetics , Dwarfism/genetics , Glucuronosyltransferase/genetics , Marfan Syndrome/genetics , Mutation , Osteochondrodysplasias/genetics , Phenotype , Skin Diseases, Genetic/genetics , Adolescent , Antley-Bixler Syndrome Phenotype/pathology , Arachnodactyly/pathology , Bone Diseases/genetics , Bone Diseases/pathology , Craniosynostoses/pathology , Dwarfism/pathology , Female , Humans , Marfan Syndrome/pathology , Osteochondrodysplasias/pathology , Skin Diseases, Genetic/pathologyABSTRACT
Mesenchymal hamartoma of the chest wall is a rare benign nonneoplastic lesion of infancy arising from chondro-osseous tissue. Although its natural history suggests spontaneous regression, we describe a fatal case in a neonate with significant respiratory compromise. We explored the use of electrical impedance tomography to evaluate the dynamic impact of such space occupying lesions on a ventilated infant.
Subject(s)
Bone Diseases/diagnostic imaging , Hamartoma/diagnostic imaging , Mesenchymoma/diagnostic imaging , Thoracic Wall/diagnostic imaging , Tomography, X-Ray Computed/methods , Bone Diseases/congenital , Electric Impedance , Female , Hamartoma/congenital , Humans , Infant, Newborn , Mesenchymoma/congenital , Ribs/diagnostic imagingABSTRACT
COPI is a key mediator of protein trafficking within the secretory pathway. COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates responsible for trafficking numerous proteins, including Golgi-resident enzymes. Here, we identify GORAB, the protein mutated in the skin and bone disorder gerodermia osteodysplastica, as a component of the COPI machinery. GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB mutations perturb Scyl1 binding or GORAB assembly into domains, indicating the importance of these interactions. Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica.
Subject(s)
Carrier Proteins/metabolism , Coat Protein Complex I/metabolism , Enzymes/metabolism , Golgi Apparatus/metabolism , Adaptor Proteins, Vesicular Transport , Bone Diseases/congenital , Bone Diseases/genetics , Bone Diseases/metabolism , Carrier Proteins/genetics , Cells, Cultured , Coat Protein Complex I/genetics , DNA-Binding Proteins , Dwarfism/genetics , Dwarfism/metabolism , Glycosylation , Golgi Matrix Proteins , HEK293 Cells , HeLa Cells , Humans , Mutation , Protein Binding , Protein Transport , RNA Interference , Skin Diseases, Genetic/genetics , Skin Diseases, Genetic/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Bone and marrow are the two facets of the same organ, in which bone and hematopoietic cells coexist and interact. Marrow and skeletal tissue influence each-other and a variety of genetic disorders directly targets both of them, which may result in combined hematopoietic failure and skeletal malformations. Other conditions primarily affect one organ with secondary influences on the other. For instance, various forms of congenital anemias reduce bone mass and induce osteoporosis, while osteoclast failure in osteopetrosis prevents marrow development reducing medullary cavities and causing anemia and pancytopenia. Understanding the pathophysiology of these conditions may facilitate diagnosis and management, although many disorders are presently incurable. This article describes several congenital bone diseases and their relationship to hematopoietic tissue.
Subject(s)
Bone Diseases/congenital , Hematologic Diseases/congenital , Bone Diseases/physiopathology , Bone Marrow/pathology , Bone Marrow/physiopathology , Bone and Bones/abnormalities , Bone and Bones/pathology , Bone and Bones/physiopathology , Hematologic Diseases/physiopathology , Hematopoiesis , Humans , Osteoclasts/pathologyABSTRACT
RATIONALE: Multiple diaphyseal sclerosis (MDS), known as Ribbing disease, is a rare congenital bone disease resulting from autosomal recessive inheritance. The case study involved a 22-year-old female patient who had been diagnosed with chronic sclerosing osteomyelitis due to lack of knowledge about MDS. Previous studies reported rarely on this condition. PATIENT CONCERNS: A 22-year-old female with MDS was analyzed. DIAGNOSES: MDS is characterized radiographically by a fusiform widening of the diaphyseal portion of the long bones, which is caused by a thickening of the cortex with obstruction of the medullary cavity. The pathologies are observed utilizing diagnostic imagery and are often difficult to identify. INTERVENTION: The patient was following a suggested regimen of oral celecoxib capsules at 200âmg/day for 6 days. OUTCOMES: The patient's diagnosis was revised to the rare condition of Ribbing disease by reviewing the clinical history and distinctive radiography images and because the symptoms were alleviated by celecoxib capsule. We also present a review of the literature on the diagnosis and differential diagnosis of MDS based on clinical and imaging features. LESSONS: MDS is rare and may often be initially misdiagnosed as another type of sclerosing bone dysplasia, thus, it is important to be aware of the existence of MDS. Once MDS is suspected, differential diagnosis should be performed to exclude other sclerosing bone dysplasias, taking into account clinical history, distinctive radiographic appearance, distribution, and laboratory and histopathologic findings. Laboratory evaluation and pathologic findings are nonspecific but assist in excluding other diagnoses. More evidence is needed to illustrate the effectiveness of medical or surgical treatments for patients with MDS.
Subject(s)
Bone Diseases/congenital , Bone Diseases/diagnostic imaging , Camurati-Engelmann Syndrome/diagnostic imaging , Osteoma, Osteoid/diagnostic imaging , Osteomyelitis/diagnosis , Administration, Oral , Camurati-Engelmann Syndrome/drug therapy , Camurati-Engelmann Syndrome/pathology , Celecoxib/administration & dosage , Celecoxib/therapeutic use , Cyclooxygenase 2 Inhibitors/administration & dosage , Cyclooxygenase 2 Inhibitors/therapeutic use , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging/methods , Osteoma, Osteoid/drug therapy , Osteoma, Osteoid/pathology , Radiography/methods , Treatment Outcome , Young AdultABSTRACT
Bone density impairment represents an established complication in adults with neurofibromatosis type 1, while few data exist in the pediatric population. Age- and gender-adjusted bone mass decreases with age and pubertal development, identifying childhood as the best time frame to introduce prevention strategies aiming at peak bone mass achievement. PURPOSE: The present study aims at evaluating bone mineral density (BMD) in a population of children with neurofibromatosis type I (NF-1), with particular focus on changes occurring during growth and pubertal development. METHODS: Bone metabolic markers and bone status [by dual-energy X-ray absorptiometry scans (DXA) of the total body and lumbar spine with morphometric analysis] were assessed in 50 children (33 males; mean age ± SD, 11.6 ± 4 years). Bone mineral apparent density (BMAD), trabecular bone score (TBS), and bone strain (BS) of the lumbar spine (LS) DXA were also obtained. RESULTS: In our cohort areal BMD (aBMD) Z-score was below the mean in 88% of the patients at LS (70% after correction for bone size) and in 86% considering total body (TB) DXA. However, aBMD Z-score was < - 2 in 12% after correction for bone size at LS and TB, respectively. Lumbar spine aBMD Z-score (r = - 0.54, P < 0.0001), LS BMAD Z-score (r = - 0.53, P < 0.0001), and TB Z-score (r = - 0.39, P = 0.005) showed a negative correlation with growth and pubertal development (P = 0.007, P = 0.02, P = 0.01, respectively), suggesting that patients failed to gain as much as expected for age. CONCLUSION: Bone density impairment becomes more evident with growth and pubertal development in NF-1 patients, thus identifying childhood as the best time frame to introduce prevention strategies aiming at peak bone mass achievement. TBS and BS, providing bone DXA qualitative information, could be useful during longitudinal follow-up for better characterizing bone impairment in these patients.
Subject(s)
Absorptiometry, Photon/methods , Aging/physiology , Bone Diseases/diagnostic imaging , Neurofibromatosis 1/diagnostic imaging , Puberty/physiology , Adolescent , Bone Density , Bone Development , Bone Diseases/congenital , Cancellous Bone/diagnostic imaging , Child , Cohort Studies , Female , Humans , Lumbar Vertebrae/diagnostic imaging , Male , Neurofibromatosis 1/complications , Neurofibromatosis 1/physiopathologyABSTRACT
Gerodermia osteodysplastica (GO) is characterized by skin laxity and early-onset osteoporosis. GORAB, the responsible disease gene, encodes a small Golgi protein of poorly characterized function. To circumvent neonatal lethality of the GorabNull full knockout, Gorab was conditionally inactivated in mesenchymal progenitor cells (Prx1-cre), pre-osteoblasts (Runx2-cre), and late osteoblasts/osteocytes (Dmp1-cre), respectively. While in all three lines a reduction in trabecular bone density was evident, only GorabPrx1 and GorabRunx2 mutants showed dramatically thinned, porous cortical bone and spontaneous fractures. Collagen fibrils in the skin of GorabNull mutants and in bone of GorabPrx1 mutants were disorganized, which was also seen in a bone biopsy from a GO patient. Measurement of glycosaminoglycan contents revealed a reduction of dermatan sulfate levels in skin and cartilage from GorabNull mutants. In bone from GorabPrx1 mutants total glycosaminoglycan levels and the relative percentage of dermatan sulfate were both strongly diminished. Accordingly, the proteoglycans biglycan and decorin showed reduced glycanation. Also in cultured GORAB-deficient fibroblasts reduced decorin glycanation was evident. The Golgi compartment of these cells showed an accumulation of decorin, but reduced signals for dermatan sulfate. Moreover, we found elevated activation of TGF-ß in GorabPrx1 bone tissue leading to enhanced downstream signalling, which was reproduced in GORAB-deficient fibroblasts. Our data suggest that the loss of Gorab primarily perturbs pre-osteoblasts. GO may be regarded as a congenital disorder of glycosylation affecting proteoglycan synthesis due to delayed transport and impaired posttranslational modification in the Golgi compartment.
Subject(s)
Bone Diseases/congenital , Dwarfism/metabolism , Osteoblasts/pathology , Proteoglycans/metabolism , Skin Diseases, Genetic/metabolism , Transforming Growth Factor beta/metabolism , Vesicular Transport Proteins/metabolism , Animals , Bone Diseases/metabolism , Bone Diseases/pathology , Cell Differentiation , Decorin/metabolism , Dermatan Sulfate/metabolism , Disease Models, Animal , Dwarfism/pathology , Female , Fractures, Bone/genetics , Glycosylation , Golgi Matrix Proteins , Mesenchymal Stem Cells/pathology , Mesenchymal Stem Cells/physiology , Mice, Inbred C57BL , Mice, Transgenic , Osteoblasts/metabolism , Signal Transduction , Skin Diseases, Genetic/pathology , Vesicular Transport Proteins/geneticsSubject(s)
Endocrine System Diseases/congenital , Infant, Newborn, Diseases , Adrenal Hyperplasia, Congenital , Adrenal Insufficiency/congenital , Adrenal Insufficiency/drug therapy , Bone Diseases/congenital , Congenital Hypothyroidism , Diabetes Mellitus/congenital , Early Diagnosis , Glucocorticoids/therapeutic use , Humans , Hyperinsulinism/congenital , Hypoglycemia/congenital , Hypopituitarism/congenital , Infant, Newborn , Intensive Care Units, Neonatal , Pituitary ACTH Hypersecretion/congenital , Thyrotoxicosis/congenital , Turner Syndrome/diagnosisABSTRACT
Geroderma osteodysplasticum (GO) has clinical and histological features that overlap with other causes of wrinkly skin. Here we present the case of a child diagnosed with GO following exome sequencing of a panel of genes covering the wide differential diagnosis. The histological features of the overlapping conditions are presented, highlighting the utility of panel testing for conditions of this type. This is relevant to many genetic conditions and can influence ongoing management as exemplified by this case.
Subject(s)
Bone Diseases/congenital , Dwarfism/diagnosis , Dwarfism/genetics , Dwarfism/pathology , Skin Diseases, Genetic/diagnosis , Skin Diseases, Genetic/genetics , Skin Diseases, Genetic/pathology , Bone Diseases/diagnosis , Bone Diseases/genetics , Bone Diseases/pathology , Cutis Laxa/diagnosis , Exome , Female , Humans , Infant , Infant, Newborn , MutationABSTRACT
Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (GorabPrx1) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the GorabPrx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that GorabPrx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared (FTIR) imaging indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the GorabPrx1 tibiae (pâ¯<â¯.05), suggesting delayed mineralization. In vivo strain gauge measurement and finite element analysis showed â¼two times higher tissue-level strains within the GorabPrx1 tibiae relative to LC tibiae when subjected to axial compressive loads of the same magnitude. Three-point bending tests suggested that GorabPrx1 tibiae were weaker and more brittle, as indicated by decreasing whole-bone strength (46%), stiffness (55%), work-to-fracture (61%) and post-yield displacement (47%). Many of these morphological and biomechanical characteristics of the GorabPrx1 tibia recapitulated changes in other animal models of skeletal aging. Future studies are necessary to confirm how our observations might guide the way to a better understanding and treatment of GO.
Subject(s)
Aging, Premature/diagnostic imaging , Bone Diseases/congenital , Dwarfism/diagnostic imaging , Skin Diseases, Genetic/diagnostic imaging , Tibia/diagnostic imaging , Adaptor Proteins, Vesicular Transport , Aging, Premature/physiopathology , Animals , Biomechanical Phenomena , Bone Density , Bone Diseases/diagnostic imaging , Bone Diseases/physiopathology , DNA-Binding Proteins , Disease Models, Animal , Dwarfism/physiopathology , Female , Fractures, Bone/genetics , Homeodomain Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , Protein Kinases/genetics , Skin Diseases, Genetic/physiopathology , Tibia/physiopathology , X-Ray MicrotomographyABSTRACT
Geroderma osteodysplastica (GO) is a subtype of cutis laxa syndrome characterized by congenital wrinkly skin, a prematurely aged face, extremely short stature, and osteoporosis leading to recurrent fractures. GO exhibits an autosomal recessive inheritance pattern and is caused by loss-of-function mutations in GORAB, which encodes a protein important for Golgi-related transport. Using whole exome sequencing, we identified novel compound heterozygous nonsense mutations in the GORAB in a GO patient. The patient was a 14-year-old Japanese boy. Wrinkled skin and joint laxity were present at birth. At 1 year of age, he was clinically diagnosed with cutis laxa syndrome based on recurrent long bone fractures and clinical features, including wrinkled skin, joint laxity, and a distinctive face. He did not show retarded gross motor and cognitive development. At 11 years of age, he was treated with oral bisphosphonate and vitamin D owing to recurrent multiple spontaneous fractures of the vertebral and extremity bones associated with a low bone mineral density (BMD). Bisphosphonate treatment improved his BMD and fracture rate. Whole exome sequencing revealed two novel compound heterozygous nonsense mutations in the GORAB gene (p.Arg60* and p.Gln124*), and the diagnosis of GO was established. GO is a rare connective tissue disorder. Approximately 60 cases have been described to date, and this is the first report of a patient from Japan. Few studies have reported the effects of bisphosphonate treatment in GO patients with recurrent spontaneous fractures. Based on this case study, we hypothesize that oral bisphosphonate and vitamin D are effective and safe treatment options for the management of recurrent fractures in GO patients. It is important to establish a precise diagnosis of GO to prevent recurrent fractures and optimize treatment plans.
Subject(s)
Bone Diseases/congenital , Carrier Proteins/genetics , Codon, Nonsense , Dwarfism/genetics , Skin Diseases, Genetic/genetics , Adolescent , Bone Diseases/diagnosis , Bone Diseases/drug therapy , Bone Diseases/genetics , Dwarfism/diagnosis , Dwarfism/drug therapy , Exome , Golgi Matrix Proteins , Heterozygote , Humans , Japan , Male , Skin Diseases, Genetic/diagnosis , Skin Diseases, Genetic/drug therapyABSTRACT
Involvement of the skeletal system by congenital syphilis is well documented in the literature, chiefly in the form of radiologic studies, including periostitis, osteitis, and osteochondritis. Because congenital syphilis is generally recognized clinically, tissue biopsy is virtually never performed. Therefore, the histopathologic findings are less well documented and mostly exist in the older literature. We report herein the clinicoradiologic and pathologic features of a 2-month-old infant who initially presented with absence of left arm movement. Radiographs of the left humerus revealed a mid diaphyseal cortical irregularity/lytic lesion and periosteal reaction. Follow-up skeletal survey showed similar findings in other extremity long bones. A bone biopsy of the humeral lesion revealed a destructive fibrohistiocytic process composed of a sheet-like proliferation of epithelioid to spindled histiocytes, without obvious granulomas, accompanied by occasional lymphocytes and neutrophils with rare plasma cells. Immunohistochemical stains showed diffuse positivity for CD31, CD68, and S-100, but CD1a was negative. Initially, the case was interpreted as "atypical fibrohistiocytic proliferation," favoring Langerhans cell histiocytosis. A few days later the results of serologic testing revealed a rapid plasma reagin of 1:256. Immunostaining for Treponema pallidum on the initial biopsy confirmed the presence of innumerable spirochetes, with a predilection for blood vessels. The patient was treated with a 10-day course of intravenous penicillin with complete resolution of the bone lesions and resulting symptomatology. To our knowledge, the above pathologic features of congenital syphilis of bone, especially in regards to its mimicry of childhood histiocytoses, have not been previously reported.
Subject(s)
Bone Diseases/diagnosis , Bone Diseases/microbiology , Histiocytosis/diagnosis , Syphilis, Congenital/diagnosis , Bone Diseases/congenital , Diagnosis, Differential , Humans , Infant , MaleABSTRACT
Cutis laxa is a heterogeneous condition characterized by redundant, sagging, inelastic, and wrinkled skin. The inherited forms of this disease are rare and can have autosomal dominant, autosomal recessive, or X-linked inheritance. Three of the autosomal recessive cutis laxa syndromes, namely cutis laxa IIA (ARCL2A), cutis laxa IIB (ARCL2B), and geroderma osteodysplastica (GO), have very similar clinical features, complicating accurate diagnosis. Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. These conditions also share additional features, such as short stature, hypotonia, and congenital hip dislocation, but the severity and frequency of these findings are variable in each of these cutis laxa syndromes. The characteristic features for ARCL2A are abnormal isoelectric focusing and facial features, including downslanting palpebral fissures and a long philtrum. Rather, the clinical phenotype of ARCL2B includes severe wrinkling of the dorsum of the hands and feet, wormian bones, athetoid movements, lipodystrophy, cataract and corneal clouding, a thin triangular face, and a pinched nose. Normal cognition and osteopenia leading to pathological fractures, maxillary hypoplasia, and oblique furrowing from the outer canthus to the lateral border of the supraorbital ridge are discriminative features for GO. Here we present 10 Iranian patients who were initially diagnosed clinically using the respective features of each cutis laxa syndrome. Each patient's clinical diagnosis was then confirmed with molecular investigation of the responsible gene. Review of the clinical features from the cases reported from the literature also supports our conclusions.
Subject(s)
Bone Diseases/congenital , Cutis Laxa/diagnosis , Dwarfism/diagnosis , Phenotype , Skin Diseases, Genetic/diagnosis , Adult , Bone Diseases/diagnosis , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , Infant , Male , SyndromeABSTRACT
Gerodermia osteodysplastica is a recessive segmental progeroid disorder mainly characterized by wrinkled skin, generalized connective tissue weakness, infantile onset osteoporosis and normal intelligence. Coding mutations in GORAB, localized on chromosome 1q24.2, are the cause of this disease. 1q24 deletions underlie a spectrum of disorders with intellectual disability and ear abnormalities as phenotypic hallmarks. Here we report on an individual from Azerbaijan originating from a non-consanguineous couple showing short stature, cutis laxa, frequent fractures, facial dysmorphism, cup-shaped ears and intellectual disability. Sanger sequencing of GORAB revealed the seemingly homozygous missense mutation p.Ser175Phe. This mutation was detected in a heterozygous state in the clinically unaffected mother, but was absent in the healthy father. We performed copy-number investigations by high-resolution array-CGH and PCR approaches and found an ~6 Mb de novo deletion spanning 1q23.3-q24.2 in the affected boy. This novel combination of genetic defects very well explains the phenotype that goes beyond the usual presentation of gerodermia osteodysplastica. Our data provide new insight into the phenotypic spectrum of 1q23-q25 deletions and shows that the combination with another pathogenic allele can lead to more severe clinical manifestations.
Subject(s)
Abnormalities, Multiple/genetics , Bone Diseases/congenital , Chromosome Deletion , Chromosomes, Human, Pair 1/genetics , Cutis Laxa/genetics , Dwarfism/genetics , Intellectual Disability/genetics , Skin Diseases, Genetic/genetics , Azerbaijan , Bone Diseases/genetics , Child, Preschool , Facies , Humans , Male , Mutation, Missense/geneticsABSTRACT
Archaeological excavations carried out in the plague cemetery of 16th century Alghero (Sardinia) brought to light the skeleton of a male aged 35-45 years, showing anomalies of the atlas. A macroscopic and radiological study has been carried out. The first cervical vertebra is fused with the skull base, resulting in an occipitalisation of the atlas. Absence of the costal element of the left foramen transversarium, resulting in an open anterior foramen transversarium, and posterior arch defect are also observed. The atlanto-occipital junction is a complex structure, susceptible to develop different patterns of congenital defects. These anatomical variations of atlas should be considered in modern clinical practice in order to formulate a correct diagnosis and to conceive an appropriate treatment. Osteoarchaeological cases are important as, beside to ascertain the presence of congenital defects in past populations, allow an in-depth study in dry bones, which can help modern medicine in interpreting anatomical variations. We present an association of congenital anomalies of the atlanto-occipital junction, a condition rarely documented in ancient and modern human skeletal remains.
Subject(s)
Bone Diseases/congenital , Bone Diseases/pathology , Cervical Atlas/pathology , Adult , History, 17th Century , Humans , Italy , Male , Middle AgedABSTRACT
The prevalences of displacement and deformity of the medial and lateral fabellae in dogs were investigated. This was a retrospective epidemiologic study. Radiographs of canine stifle joints (1022 limbs, 534 dogs) were obtained. The images were taken at the Nihon University Animal Medical Center and three private animal hospitals from January 2003 to July 2012. The position and morphology of the medial or lateral fabella were evaluated on the radiographs. The prevalence of displacement of the medial and lateral fabellae was 1.7% and 0.3%, respectively. The prevalence of deformity of the medial and lateral fabellae was 6.9% and 4.6%, respectively. Aplasia or hypoplasia of the fabella was detected more frequently in the medial fabella. On the other hand, a bipartite or multipartite fabella was observed more frequently in the lateral fabella. Nearly all cases of displacement or deformity of the fabella occurred in dogs weighing less than 10 kg. Abnormalities of the fabella were observed in the medial and lateral fabella. We found that abnormal fabellae were closely associated with medial patellar luxation and to a lesser extent with cranial cruciate ligament rupture. No clinical signs were associated with an abnormality of the fabella, with the exception of two dogs with traumatic avulsion of the lateral head of the gastrocnemius muscle.
Subject(s)
Bone Diseases/veterinary , Dog Diseases/epidemiology , Hindlimb/pathology , Animals , Bone Diseases/congenital , Bone Diseases/epidemiology , Bone Diseases/pathology , Dog Diseases/pathology , Dogs , Female , Japan/epidemiology , Male , Retrospective StudiesABSTRACT
Peale's dolphin Lagenorhynchus australis is frequently seen off the coast of southern South America, where it feeds among coastal kelp beds and occasionally strands. We searched for macroscopic evidence of skeletal lesions in 78 specimens of Peale's dolphin from 2 museum collections, which contain almost all of the species' skeletons known in collections worldwide. Thirty-two specimens (41%) had some type of osteological abnormalities. In 21 cases (66%), congenital deformations were the most predominant abnormality found. Acquired lesions included (1) induced trauma: abnormal curvature (n=5 specimens) and fractures (n=2); (2) infectious diseases: spondylo-osteomyelitis (n=3); and (3) degenerative diseases: exostoses (n=8) and spondylosis deformans (n=4). It is noteworthy that all of these animals died incidentally in gillnet entanglement and were presumably healthy at the time of death. The effect that different osseous lesions may have on an animal's quality of life may depend on the area of the spine affected and the number of vertebrae involved.
Subject(s)
Bone Diseases/veterinary , Dolphins , Exostoses/veterinary , Spine/abnormalities , Spondylosis/veterinary , Animals , Bone Diseases/congenital , Bone Diseases/pathology , Exostoses/pathology , Female , Male , South America , Spondylosis/pathologyABSTRACT
Cephalohematomas in newborns are often managed nonsurgically and resolve within the first month of life. In cases of large hematomas (>7 cm) with delayed resorption and persistence over 4 weeks, these masses can often lead to complications of calcification, infection, or hyperbilirubinemia. We report a case of a 14-day-old child with a persistent, large, noncalcified cephalohematoma. After observation alone showed that the cephalohematoma increased in size, 100 ml of old blood was surgically evacuated on day 15 of life. The procedure required a small 1-cm incision and, unlike most large cephalohematomas evacuated after 1 month of observation, there were no signs of skull-deforming calcification observed. This case report presents the earliest evacuation of large noncalcified cephalohematomas in newborns ever reported in the literature, and suggests benefits of early surgical evacuation before 1 month of life.