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.

Schmid's Type of Metaphyseal Chondrodysplasia: Diagnosis and Management.

OBJECTIVES: There are several types of metaphyseal chondrodysplasia and various clinical types have been differentiated. The Schmid type of metaphyseal chondrodysplasia is the most common. Diffuse metaphyseal flaring, irregularity, and growth plate widening, which are most severe in the knees, are the most striking radiological features of this disease. The Schmid type of metaphyseal dysostosis is characterized by failure of normal mineralization of the zone of provisional calcification, leading to widened physes and enlarged knobby metaphyses, effectively causing shortening of the tubular bones, splaying of the metaphyses, coxa vara, and bow legs. Orthopaedic interventions were primarily performed on the lower extremities. METHODS: Twelve children (seven girls and five boys) aged 7-10 years were enrolled in this study. Moderate short stature was a uniform feature associated with predominant involvement of the proximal femora and bow legs resulted in the development of angular deformities. A waddling gait was a consequence of coxa vara in eight children. Valgus osteotomy of the proximal femur was planned after physeal closure for the group of children with coxa vara. Hemiepiphysiodesis was performed to re-align the genu varum in three children. RESULTS: Other forms of metaphyseal dysostosis were ruled based on full clinical and radiographic phenotypes, with confirmation through molecular pathology. Mutations in the COL10A1 gene located on chromosome 6q21-q22.3 were confirmed. Re-alignment was accomplished in our group of patients. CONCLUSION: The most striking clinical features of Schmid metaphyseal chondrodysplasia which appear within the first 2-3 years of life are: moderate short limbs and short stature, a waddling gait, and increasing shortness of stature with age. The Schmid type of metaphyseal chondrodysplasia is a disorder that arises from defective type X collagen, which is typically found in the hypertrophic zone of the physes. Moderate short stature and a waddling gait associated with pain are the most common clinical presentations. Osteotomies to correct bow legs are sometimes combined with lengthening procedures. Recurrence of the deformities with growth is not uncommon; therefore, hemiepiphysiodesis or stapling might be indicated in some cases.

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.