A constellation of orthopaedic deformities in connection with cartilage oligomeric matrix protein mutation.

BACKGROUND: Trendelenburg's gait can be observed in Legg-Calvé-Perthes disease, antalgic gait observed in osteoarthropathy and waddling gait is usually seen in genu varum and circumduction gait in patients with genu valgum. Disabling pain was a prime manifestation in slipped capital femoral epiphysis (SCFE). Limited joint range of motion with an inability to bear full weight on an affected extremity with swaying and wide-based gait is seen in patients with malalignment of the lower limbs. All the above-mentioned deformities have been labelled as idiopathic. The main objective of this article is to approach to the aetiology understanding. PATIENTS AND METHODS: Ten children (3 girls and 7 boys with age average of 9 years) presented with variable deformities; Perthes-like deformity, genu varum/valgum and osteoarthropathy and one patient with SCFE. Clinical and radiological phenotypes were the baseline tool of diagnosis. Genotypic characterisations were performed. RESULTS: Diverse clinical presentations of Perthes-like disease, osteoarthropathy, genu varum/valgum and SCFE were the most prominent skeletal abnormalities in patients manifested cartilage oligomeric matrix protein (COMP) gene mutation. CONCLUSION: : The value of presenting this article is fourfold; first to signify that mutation study was essential for the increment of knowledge related to the genotype-phenotype relationships. Second, to indicate that professional awareness is needed to differentiate between the hidden pathologies in patients with Perthes-like deformity, genu varum, genu valgum and early osteoarthritis in correlation with COMP gene mutation. Third, it is mandatory to question the validity of the term idiopathic. Fourth, this article is an attempt to sensitise orthopaedic physicians and surgeons that deformities might be stemmed from diverse forms of intrinsic bone disorders.

How frequent is osteogenesis imperfecta in patients with idiopathic osteoporosis?: Case reports.

RATIONALE: The term idiopathic osteoporosis itself is quite a non-specific disease label, which fails to address the etiological understanding. Bone mineral density alone is not a reliable parameter to detect patients at high risk of fracture. The diversity of the clinical phenotypes of discolored teeth, blueness of the sclera, back and joint pain, cardiovascular disease, Diabetes type II, hearing problems and a long list of orthopedic problems are have to be considered. PATIENTS CONCERNS: Our study has been designed in accordance with the clinical and radiological phenotype of eleven index cases with the provisional diagnosis of OI, which was followed by genotypic confirmation. This was followed by the invitation of siblings, parents, grandparents and other relatives to participate in the interviews, and to discuss the impact of the diagnosis. Proper collaboration with these families facilitated the process to identify other subjects with a history of fractures and other deformities/disabilities which were seemingly correlated to heritable connective tissue disorder. In total, 63 patients (27 children and 36 parents/grandparents and relatives) were enrolled in the study. Two groups of children were not included in our study. We excluded children with incomplete documentation and children who manifested de novo mutation. The term idiopathic osteoporosis (IOP) has been given to these families in other Institutes and was considered as a definite diagnosis. IOP was solely based on T scores, BMD and certain laboratory tests. Surprisingly, no single adult patient underwent clinical and or radiological phenotypic characterization. DIAGNOSES: A constellation of significant disease associations with osteoporotic fracture risk have been encountered. The index cases showed mutations in COL1A1 (17q21.31.q22) and COL1A2 (7q22.1), the genes encoding collagen type I. The phenotype/genotype confirmation in 11 children was the key factor to boost our research and to re-consult each family. Comprehensive clinical and radiological phenotypic documentation has been applied to most of other family subjects who principally received the diagnosis of IOP. INTERVENTIONS: All adult patients had normal serum calcium and only three patients showed an average of low serum phosphate of 0.7-0.61 mmol/l. Serumcrosslaps in six parents was in the average of (2.9-3.8 nM) and PTH levels were normal in all patients (the average showed 8.73 pg/ml). OUTCOMES: Our efforts to minimize and constrain the usage of the term idiopathic osteoporosis and to understand the sequence of pathological events that occurred in these families were emphasized. These efforts evolved into a remarkable and unique constellation of clinical findings. Strikingly, fracture represented a portion in a series of skeletal and extra-skeletal deformities and abnormalities which are all correlated to connective tissue disorder. This was achieved mainly through comprehensive phenotype/genotype confirmation, followed by scrutinizing the records of each family, clinical examination of the adults and revising the archives of our Hospitals and other Institutes. LESSONS: The sequence of diverse pathological events recorded within each family would be almost incomprehensible without a proper etiological understanding of the natural history of each child/family deformity that led to their occurrences. We wish to stress that, our current study is just an attempt to cover only a tiny fraction of the tip of the iceberg and to profoundly explore one of the most under-estimated causes of idiopathic osteoporosis.

Corrections of diverse forms of lower limb deformities in patients with mucopolysaccharidosis type IVA (Morquio syndrome).

BACKGROUND: Thoracolumbar kyphosis has been considered as the first presenting deformity and is often a key diagnostic clue noted in children with mucopolysaccharidosis (MPS) type IV (Morquio's syndrome). However, we observed that the progressive irregularities of the epiphyses of the long bones were the most prominent skeletal pathology, causing effectively the development of diverse forms of lower limbs deformities with extreme variation in age of onset. MATERIALS AND METHODS: Ten patients (seven children and three adults) with an average age of 15 years have been enrolled in this study. Age of diagnosis of MPS IVA has a variable age of onset and a MISLEADING rate of severity. Hip dislocations, genu valgum, protrusio acetabuli and osteoarthritis were the most common lower limbs deformities in these patients. Clinical and radiographic phenotypes were the baseline tools of documentation. Urinary screening and genotypic characterizations have been applied accordingly. RESULTS: Combined pelvic and femoral procedures for hip dislocation, epiphysiodeses and supracondylar osteotomy for genu valgum and hip arthroplasty for protrusio acetabuli have been performed. All patients manifested insufficient activity of N-acetylgalactosamine-6-sulphate sulphatase, an enzyme that degrades keratin sulphate and chondroitin-6 sulphate. CONCLUSION: The extensive clinical heterogeneity contributed significantly in the delay in establishing the diagnosis particularly in adult patients with MPS IV. The epiphyseal irregularities of the long bones and the progressive flattening pathology of MPS IV A were the reason to falsely diagnose some patients as spondyloepiphyseal dysplasia congenital and/or tarda. Proximal femoral osteotomy, realignment osteotomy and total hip arthroplasty have been performed for coxa vara, genu valgum and protrusio acetabuli, respectively, in children and adult group of patients. The importance of early diagnosis on MPS IV A is to receive enzyme replacement therapy and plan for other therapeutic measures.

Acetabular roof stress fracture: a rare cause of hip pain in children.

Stress fracture of acetabular roof is an unusual cause of hip pain. It is considered as an underdiagnosed entity. People who are more susceptible to experience this fracture are athletes, soldiers and dancers. We present the case of an 11 year old girl with a roof acetabular stress fracture for which the diagnosis and follow-ups were possible by the means of MRI. The treatment was keeping the child at a complete rest. Failure to abide with this treatment can cause the stress fracture to evaluate into a complete fracture.

Is webbing (pterygia) a constant feature in patients with Escobar syndrome?

We describe two unrelated patients aged 9 and 12 years. The first patient presented with multiple congenital contractures not associated with webbing (pterygia). Interestingly, his genetic testing showed the typical genotypic criteria of Escobar syndrome (CHRNG heterozygous mutation). The characteristics of the second child were compatible with the phenotypic and genotypic criteria for Escobar syndrome. Both patients manifested the typical facial features suggestive of Escobar syndrome. The aim of this paper is twofold: first, to illustrate that the absence of popliteal webbing is not a sufficient reason to exclude Escobar syndrome in patients with multiple contractures and second, dysmorphic facial features and the presence of certain radiological abnormalities might be considered baseline diagnostic tools in favor of this syndromic entity.

Multi slice computed tomography approach in the assessment of supracondylar humeral fractures in children.

The purpose of this study was to assess the impact of Multi Slice Computed Tomography (MSCT) on the understanding of the spatial displacement of supracondylar humeral (SCH) fractures, their classification and their management. A prospective study was conducted on 63 children with SCH fractures Gartland II or Lagrange 2 and 3, over a period of 30 months. The patients were 42 boys and 21 girls, aged between 3 and 14. All patients were imaged using conventional radiography. Thirty-two patients underwent MSCT and 3-dimensional reconstructions. According to the Lagrange classification system, 16 patients had type 2 fractures and 47 had type 3 fractures. In type 2, the posterior cortices of both medial and lateral columns were bent on CT (n = 6). In type 3, CT-scan made it possible to distinguish two subgroups. In the first subgroup (n = 12) there was fracture of both anterior and posterior cortices of the lateral column; however, the posterior cortical surface of the medial column was preserved. In the second subgroup (n = 14), there was no cortical surface contact in the medial column, but the continuity of the posterior cortical surface of the lateral column was preserved. Based on a new concept of column stability, the use of CT-scan has allowed for a better understanding of supracondylar fractures in children.

Split hand/split foot deformity with focal dermal hypoplasia (Goltz syndrome).

We report on a-6-months-old girl who manifested the phenotypic features of focal dermal hypoplasia. Significant limb deformities in connection with typical skin changes were documented. The family history had a high frequency of spontaneous abortions and male stillbirths. Male stillbirths are a landmark in favour of X-linked dominant pattern of inheritance. Despite the severe hand/foot deformities, the skull base and the tubular bones were sclerotic.

Magnetic resonance evaluation of acetabular residual dysplasia in developmental dysplasia of the hip: a preliminary study of 27 patients.

Thirty-one hips in 27 young girls, treated for developmental dysplasia of the hip in the authors' institute since 2003, showed persistent radiographic evidence of residual acetabular dysplasia. These hips were registered as candidates for pelvic osteotomy. A prospective study was conducted and these hips were evaluated by magnetic resonance imaging (MRI); the average age of the patients was 5 years. MRI measurement of acetabular angle and acetabular head index in 2 different landmarks (bone and cartilage) was performed. The results were correlated with plain radiographic film evolution. MRI studies revealed sufficient cartilaginous acetabular coverage in 27 hips, cartilaginous acetabular dysplasia in 2 hips, and short acetabulum in 2 others. The 27 hips with thick cartilage of the acetabular roof were subsequently followed up by plain radiographs. The average follow-up period was 2.1 years. The authors observed a spontaneous progressive ossification of the cartilaginous acetabular roof in all the 27 cases. In 4 cases, the correction of the acetabular angle was complete. They concluded that MRI promotes more accurate selection of patients for pelvic osteotomy and aids in the choice of the most appropriate type of osteotomy. Clinical imaging examples are presented and need to be further evaluated.

Distinctive tomographic features of atlantoaxial dislocation in a boy with acromesomelic dysplasia du Pan syndrome.

Distinctive tomographic features of atlantoaxial dislocation have been encountered in a child with du Pan syndrome. Three-dimensional computed tomography scan showed agenesis of the odontoid process associated with significant hypoplasia of the left lateral mass of the odontoid. Bidirectional fluorescent DNA sequencing have been used to identify mutations in the complete coding region (exon 1-2) of the cartilage-derived morphogenic protein 1 gene. No mutation was detected in the analysed region. We report what might be a novel variant of acromesomelic du Pan syndrome.

Atlanto-axial segmentation defects and os odontoideum in two male siblings with opsismodysplasia.

We report two siblings aged 11 and 7 years, respectively, who presented with the clinical and radiographic features of opsismodysplasia (non-lethal type). 3D computed tomography scans of the craniocervical region revealed a split atlas and os odontoideum in both siblings. To the best of our knowledge, this is the first clinical report detailing craniocervical malformations in two siblings with opsismodysplasia.

Early results of the Ponseti method using the Steenbek foot abduction brace: a prospective study of 95 feet.

The purpose of this study is to evaluate the early results of the Ponseti method and the effectiveness of the Steenbek foot abduction brace. A total of 74 patients with 110 idiopathic clubfeet were included in this prospective study. The feet were evaluated according to the Dimeglio-Bensahel classification, the Catteral-Pirani classification and the functional classification of the Hospital for Joint Diseases. Ninety-eight feet (89%) had a good result after the casting period. All the feet evaluated after the period of full-time bracing and during the period of part-time bracing showed a good correction. The Ponseti method using the Steenbek foot abduction brace is effective in correcting idiopathic clubfeet.

A hypoplastic atlas and long odontoid process in a girl manifesting phenotypic features resembling spondyloepimetaphyseal dysplasia joint laxity syndrome.

Phenotypic features consistent but not completely diagnostic for spondyloepimetaphyseal dysplasia joint laxity (SEMDJL) were encountered in a 7-year-old-girl. Additional tomographic features of a hypoplastic atlas (assimilation of the posterior arch of the atlas) and unduly long odontoid process were seen. We report what might be a novel type of SEMDJL.

Asymmetrical skull, ptosis, hypertelorism, high nasal bridge, clefting, umbilical anomalies, and skeletal anomalies in sibs: is Carnevale syndrome a separate entity?

A group of syndromes, consisting of Malpuech syndrome, Michels syndrome, Carnevale syndrome, OSA syndrome, and Mingarelli syndrome share the combination of symptoms of highly arched eyebrows, ptosis, and hypertelorism, and vary in other symptoms such as asymmetry of the skull, eyelid, and anterior chamber anomalies, clefting of lip and palate, umbilical anomalies, and growth and cognitive development. It has been suggested that they are in fact part of the same entity. Here, we describe a brother and sister with the same constellation of symptoms, and compare these with the various entities. We conclude that the present patients resemble most patients with Carnevale and Mingarelli syndrome, and the case reported by Guion-Almeida, and that these patients form together most probably the same entity. We suggest the name Carnevale syndrome as this author described this combination of symptoms for the first time. Malpuech and Michels syndromes are probably separate entities, although they may still be allelic. Pattern of inheritance of Carnevale syndrome is most likely autosomal recessive.

A novel form of ischio-vertebral syndrome.

We report a boy with ischial hypoplasia, vertebral malsegmentation and multiple other skeletal anomalies which do not fit well with any previously-described disorder. The proband's brother and mother were also slightly affected. We review the pertinent literature, discuss the differential diagnosis and suggest that this may be a previously unreported autosomal dominant disorder, with variable penetrance.We believe that the clinical and radiological features of various syndromes with ischial aplasia/hypoplasia and vertebral malsegmentation are not sufficiently different to justify the current separate categories of "ischio-vertebral dysplasia" and "ischio-spinal dysostosis". We suggest that the term "ischio-vertebral syndrome" should be used until identification of genes affecting ischial and axial morphogenesis is completed.

Progressive non-infectious anterior vertebral fusion, split cord malformation and situs inversus visceralis.

BACKGROUND: Progressive non-infectious anterior vertebral fusion is a unique spinal disorder with distinctive radiological features. Early radiographic findings consist of narrowing of the anterior aspect of the intervertebral disk with adjacent end plate erosions. There is a specific pattern of progression. The management needs a multi-disciplinary approach with major input from the orthopaedic surgeon. CASE REPORT: We report a 12-year-old-female with progressive anterior vertebral fusion. This occurred at three vertebral levels. In the cervical spine there was progressive fusion of the lateral masses of the Axis with C3. Secondly, at the cervico-thoracic level, a severe, progressive, anterior thoracic vertebral fusion (C7-T5) and (T6-T7) resulted in the development of a thick anterior bony ridge and massive sclerosis and thirdly; progressive anterior fusion at L5-S1. Whereas at the level of the upper lumbar spines (L1) a split cord malformation was encountered. Situs inversus visceralis was an additional malformation. The role of the CT scan in detecting the details of the vertebral malformations was important. To our knowledge, neither this malformation complex and nor the role of the CT scan in evaluating these patients, have previously been described. CONCLUSION: The constellations of the skeletal abnormalities in our patient do not resemble any previously reported conditions with progressive anterior vertebral fusion. We also emphasise the important role of computerized tomography in the investigation of these patients in order to improve our understanding of the underlying pathology, and to comprehend the various stages of the progressive fusion process. 3D-CT scan was performed to improve assessment of the spinal changes and to further evaluate the catastrophic complications if fracture of the ankylosed vertebrae does occur. We believe that prompt management cannot be accomplished, unless the nature of these bony malformations is clarified.

Familial vertebral segmentation defects, Sprengel anomaly, and omovertebral bone with variable expressivity.

A 10-year-old boy was found to have an unusual presentation of the Sprengel anomaly, omovertebral bones, and segmentation defects of the vertebral column at the cervical, thoracic, and sacral level. In addition, he showed hypertelorism, downslanting palpebral fissures, ptosis, webbing, and hypoplasia of the thenar and hypothenar areas. He had moderate mental delay. In addition to the segmentation defects and omovertebral bones, radiological studies showed a small pelvis and 11 pairs of ribs. Some of the features were present in the mother, and minimal symptoms were present in the father. The parents were consanguineous. A paternal cousin had segmentation defects, omovertebral bones, and a Sprengel deformity as well, although with milder presentation than the proband. We were unable to find a similar combination of manifestations in literature. The familial occurrence is best compatible with autosomal dominant inheritance, showing wide variability of expression. It is possible that the more notable signs in the proband can be explained by homozygosity for the disorder.

Siblings with glaucoma, mental retardation and short stature.

We report a sibling pair, whose parents are distantly related, with congenital glaucoma and mental retardation. There are similarities to ter Haar syndrome, but severe mental retardation has not been described previously in that condition.

Facial features and skeletal abnormalities in Larsen syndrome--a study of three generations of a Tunisian family.

We report on a 3 generation study of a Tunisian family, in which eight subjects had or have features of Larsen syndrome: three siblings, two females and one male are affected with flattened facies, multiple congenital joint dislocations, and club foot deformities. Five other family members were recognised as being variably affected with the syndrome. Over the three generations, despite the characteristic facial features being the most constant clinical signs of the syndrome, none of those still living had palatal clefts, the multiple infantile deaths in this family, however, were characterised by an association with cleft palate.

Hypohidrotic ectodermal dysplasia with tibial aplasia.

We report an inbred Tunisian family, in which 19 members had an ectodermal syndrome involving the teeth, hair, nails and skin. Ectrodactyly occurred as an isolated manifestation in one, and with tibial aplasia in two others. None had facial clefts. Dysplastic ears were part of the syndrome.