Legg-Calve-Perthes disease in a patient with Bardet-Biedl syndrome: A case report of a novel MKKS/BBS6 mutation.
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SUBMITTER: Mishima K
PROVIDER: S-EPMC7752338 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Legg-Calvé-Perthes disease in a patient with Bardet-Biedl syndrome: A case report of a novel <i>MKKS/BBS6</i> mutation.
Mishima Kenichi K Fujita Atsushi A Mizuno Seiji S Matsushita Masaki M Nagata Tadashi T Kamiya Yasunari Y Miyake Noriko N Matsumoto Naomichi N Imagama Shiro S Kitoh Hiroshi H
Clinical case reports 20200921 12
This article reports a girl with Bardet-Biedl syndrome (BBS) having a novel causative mutation who developed Legg-Calvé-Perthes disease (LCPD). There exists a possibility that the prognosis of LCPD had been adversely affected by the concomitant BBS. ...[more]
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Project description:BackgroundLegg-Calvé-Perthes Disease (LCPD) is a necrosis of the femoral head which affects the range of motion of the hips. Its incidence is variable, ranging from 0.4/100,000 to 29.0/ 100,000 children. Although LCPD was first described in the beginning of the past century, limited is known about its etiology. Our objective is to describe the main areas of interest in Legg-Calve-Perthes disease.MethodsA review of the literature regarding LCPD etiology was performed, considering the following inclusion criteria: Studies reporting clinical or preclinical results. The research group carried out a filtered search on the PubMed and Science Direct databases. To maximize the suitability of the search results, we combined the terms ''Perthes disease" OR "LCPD" OR "children avascular femoral head necrosis" with "diagnostic" OR "treatment" OR "etiology" as either key words or MeSH terms.ResultsIn this article been described some areas of interest in LCPD, we include topics such as: history, incidence, pathogenesis, diagnosis, treatment and possible etiology, since LCPD has an unknown etiology.ConclusionsThis review suggests that LCPD has a multifactorial etiology where environmental, metabolic and genetic agents could be involved.
| S-EPMC8922924 | biostudies-literature
Project description:PurposeTo identify the causative mutation in two siblings from a consanguineous family in India with retinitis pigmentosa (RP) and polydactyly without other findings of Bardet-Biedl syndrome (BBS). We also performed functional characterization of the mutant protein to explore its role in this limited form of BBS.MethodsThe siblings underwent a thorough ophthalmological examination, including retinal optical coherence tomography (OCT) imaging, and an extensive physical examination with abdominal ultrasonography to characterize the disease phenotype. Next-generation sequencing (NGS) using a panel targeting retinal degeneration genes was performed on genomic DNA samples from the siblings and parents. Upon identification of the causative mutation, functional characterization was accomplished by performing protein-protein interaction studies in human embryonic kidney (HEK-293T) and human adult retinal pigmented epithelium (ARPE-19) cells.ResultsThe two siblings showed signs of RP and polydactyly. The patients did not have truncal obesity, renal anomalies, hydrometrocolpos, congenital heart disease, or overt cognitive defects. NGS identified a homozygous c.1184A>G mutation in the MKKS/BBS6 gene in both patients resulting in a p.H395R substitution in the MKKS/BBS6 protein. This mutant protein decreased the interaction of MKKS/BBS6 with BBS12 but did so to a different extent in the HEK-293T versus ARPE-19 cells. Nonetheless, the effect of the H395R variant on disrupting interactions with BBS12 was not as profound as other reported MKKS/BBS6 mutations associated with syndromic RP.ConclusionsWe identified a novel H395R substitution in MKKS/BBS6 that results in a unique phenotype of only RP and polydactyly. Our observations reaffirm the notion that mutations in MKKS/BBS6 cause phenotypic heterogeneity and do not always result in classic MKKS or BBS findings.
| S-EPMC4734152 | biostudies-literature
Project description:BackgroundLegg-Calvé-Perthes disease (LCPD) is a common public health problem that usually occurs between the ages of 4 and 8 years, but it can occur between the ages of 2 and 15 years. This condition occurs due to the interruption of blood supply to the femoral head. Up to now, different surgical and nonsurgical treatments, including femoral varus osteotomy, innominate osteotomy, pelvic osteotomies, triple osteotomy, Chiari osteotomy, and shelf acetabuloplasty, have been suggested for noncontainable LCPD hips.ObjectiveThe aim of this comprehensive review was to investigate the various surgical techniques used for LCPD.MethodsAn advanced electronic search of the English-language literature was performed from October 8 to 14, 2020. The electronic databases PubMed, MEDLINE, Web of Science, Embase, Ovid, and Google scholar were searched using appropriate search terms. A manual search of references also was performed. After retrieving the studies, duplicates were removed, and the remining studies were screened based on the title, abstract, and full text. The quality of the selected articles was assessed, and the required data were extracted from eligible articles.ResultsA total of 22 studies were included in the review. Based on the results of the reviewed studies, there are three main factors that influence the treatment outcomes in patients with Perthes disease. These factors are onset age, femoral head involvement severity, and treatment method. The disease has a poor prognosis in children over 8 years old, but this group of patients can also benefit from advanced surgical methods. In patients aged less than 6 years, the disease has a generally good prognosis, but in those aged between 6 and 8 years, its prognosis is variable. Thus, the need for surgical intervention requires close observation of signs. Once any head signs are observed, dynamic arthrography is beneficial before choosing the treatment approach.ConclusionsThis review provides clinicians with a brief guideline for the treatment of patients with LCPD.
| S-EPMC8129878 | biostudies-literature
Project description:BackgroundLegg-Calve-Perthes Disease (LCPD) is an idiopathic osteonecrosis of the developing femoral head complicated by pain and disability of the hip joint. To date, the pathological mechanisms of LCPD are not well-known. This study screened the changes in serum protein expression in patients with LCPD.MethodsAge- and sex-matched serum samples from 10 control subjects and 10 patients with LCPD were compared using the isobaric tags for relative and absolute quantification (iTRAQ) technique. Gene ontology analyses, KEGG pathway and functional network analyses were performed. Proteins of interest with large differences in expression, S100-A8, alpha-1-acid glycoprotein 1, haptoglobin and apolipoprotein E, were compared by western blotting.ResultsThe disease/control ratios showed 26 proteins were significantly differentially expressed (all p < 0.05). Including higher abundances of complement factor H (1.44), complement C4-B (1.45), isocitrate dehydrogenase [NAD] subunit alpha (2.7) alpha-1-acid glycoprotein 1 (1.87), heptoglobin (1.53) and Ig lambda-2 chain C regions (1.46), and lower levels of apolipoprotein E (0.50), apolipoprotein F (0.60), apolipoprotein C-III (0.69), S100-A8 (0.73), S100-A9 (0.75) and prothrombin (0.77) in LCPD than in controls. The alpha-1-acid glycoprotein 1 and haptoglobin increases, and apolipoprotein E and S100-A8 decreases were confirmed by western blot. KEGG pathway analysis revealed these proteins were related to the complement and coagulation cascades, Staphylococcus aureus infection, PPAR signaling, fat digestion and absorption, and vitamin digestion and absorption. Functional network analysis suggested that the proteins were involved in lipid regulation.ConclusionsThe complement and coagulation cascades, and abnormal lipid metabolism may be involved in the pathogenesis of LCPD.
| S-EPMC4595068 | biostudies-literature
Project description:BackgroundTotal hip replacement (THR) in patients with a history of Legg-Calvé-Perthes disease can be a technically challenging procedure due to the distorted hip morphology. We propose a technique in which THR is preceded by a modified relative femoral neck lengthening (RFNL) procedure. Hereby, we aim to restore the biomechanical parameters.MethodsTwenty-eight patients underwent RFNL in preparation of a second-stage THR between December 2011 and September 2019. The mean age was 38.1 ± 11.4 years. Radiographs were analyzed for centrotrochanteric distance, lateral displacement of the greater trochanter, and leg length discrepancy to assess the biomechanical restoration. Complication rate, reoperation rate, and patient-reported outcome measures were measured.ResultsMean centrotrochanteric distance increased from -18.7 ± 6.7 mm preoperatively to 1.9 ± 9.0 mm (P < .001) after RFNL and to 11.4 ± 10.4 mm after THR (P < .001). Mean lateral displacement of the greater trochanter increased from 34.2 ± 8.1 mm preoperatively to 42.4 ± 5.2 mm (P < .001) after RFNL and to 49.9 ± 8.3 mm after THR (P < .001). Leg length discrepancy decreased from 17.5 ± 10.5 mm to 2.7 ± 2.2 mm after THR (P < .001). Mean Harris Hip Score improved from 56.9 ± 17.6 preoperatively to 89.4 ± 10.7 at the latest follow-up (P < .001). Eight patients (8 hips) postponed THR because of sufficient clinical improvement, at a mean follow-up of 4.2 ± 2.1 years. Two hips needed a revision RFNL due to non-union (7.1%), and 1 hip replacement was revised due to a deep infection (5.0%).ConclusionsRFNL prior to THR in patients with end-stage osteoarthritis following Legg-Calvé-Perthes disease allows for utilizing regular implants with straight access to the femoral canal, with restored biomechanics and restoration of leg length. The prominent overhanging greater trochanter is reduced to prevent postoperative extra-articular impingement.
| S-EPMC8991231 | biostudies-literature
Project description:BackgroundThe purpose of this study was to examine the evolution of Legg-Calvé-Perthes' disease (LCPD) among children from British Columbia (BC), Canada who were treated non-operatively and to compare the results to a previously conducted study in India.MethodsThis was a retrospective review of patients treated non-operatively for LCPD in BC between 1990 and 2006 compared with a cohort from India. Demographic and treatment information were collected from medical records. Radiographs were assigned modified Waldenstrom, Catterall, Salter-Thompson and Herring classifications and intra- and interobserver reliability were assessed. We evaluated epiphyseal extrusion (EE) and metaphyseal width (MW), and assessed radiographs using the Mose and modified Stulberg classifications.Results102 hips (90 patients) had radiographs available for evaluation. 95% of the BC cohort presented as Waldenstrom stages I and II, whereas, 90% of the Indian cohort presented as IIIa. Final EE was similar for both groups (BC 26.8%, India 27.3%) and final MW was 119% in both groups. Modified Waldenstrom and Herring classifications had substantial intra- and interobserver reliability, while Salter-Thompson and Catterall classifications had moderate agreement at best. Most hips were Catterall IV (80%) and Herring C (89%) for the BC cohort compared to only 44% and 43% of Indian hips, respectively. Most hips were irregular according to the Mose classification (BC 43%, India 52%) and aspherical according to the Stulberg classification (BC 78%).ConclusionsWe found similar radiographic progression and final radiographic appearances of LCPD in India and BC though differences in the distribution of the classification systems warrant further study.Supplementary informationThe online version contains supplementary material available at 10.1007/s43465-021-00543-x.
| S-EPMC9043051 | biostudies-literature
Project description:BackgroundLegg-Calvé-Perthes disease is a self-limiting disorder that develops in children following interruption of the blood supply to the capital femoral epiphysis. This review outlines the current knowledge on the epidemiology, natural evolution, clinical spectrum, and management of the disease.MethodsThe literature pertaining to these aspects of the disease were studied and summarized in this review.ResultsEpidemiological studies suggest that environmental factors contribute to the causation of the disease. Incidence rates monitored over time indicate that the incidence of Legg-Calvé-Perthes disease is declining. The natural evolution followed on sequential plain radiographs enables division of the disease into Stages Ia, Ib, IIa, IIb, IIIa, IIIb, and IV. Reversible deformation of the capital occurs in Stages Ia-IIa simply on standing while irreversible deformation may occur in Stages IIb and IIIa. Treatment of Legg-Calvé-Perthes disease in Stages Ia-IIa aims to prevent the femoral head from getting deformed by containment and avoidance of weight-bearing. In Stages IIb and IIIa, treatment aims to remedy the effects of early irreversible deformation of the femoral head. In Stage IIIb and IV, treatment is directed to correcting the altered shape of the femoral head. The impression that these treatment methods are helpful is based on poor quality evidence.ConclusionThere is an urgent need to undertake Level I studies to establish the efficacy of currently treatment.Level of evidencelevel V.
| S-EPMC10549695 | biostudies-literature
Project description:Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome, MIM 253200 ) is an autosomal recessive lysosomal storage disease (LSD) caused by decreased activity of arylsulfatase B (N-acetylgalactosamine 4-sulfatase) enzyme resulting in dermatan sulfate accumulation; mucopolysaccharidosis type IVA (MPS IVA, Morquio syndrome A, MIM 253000 ) by decreased activity of N-acetylgalactosamine 6-sulfatase enzyme resulting in accumulation of keratan sulfate. Clinical symptoms include coarse facial features, joint stiffness, hepatosplenomegaly, hip osteonecrosis, and dysostosis multiplex. MPS IVA symptoms are similar but with joint hypermobility.With suspicion of MPS disease, clinicians request urine studies for quantitative and qualitative glycosaminoglycans (GAGs). Diagnosis is confirmed by decreased enzyme activity in leukocytes or cultured skin fibroblasts. Further confirmation is obtained with identification of two mutations in the ARSB gene for MPS VI or mutations in the GALNS gene for MPS IVA.We report slowly progressing patients, one with MPS VI and two with MPS IVA, who presented with skeletal changes and hip findings resembling Legg-Calvé-Perthes disease or spondyloepiphyseal dysplasia and normal/near normal urine GAG levels. The urine analysis data presented suggest that present screening techniques for MPS are inadequate in milder patients and result in delayed or missed diagnoses. The patients presented in this paper emphasize the importance of enzymatic and molecular testing.
| S-EPMC3755551 | biostudies-literature
Project description:PURPOSE:Legg-Calvé-Perthes disease (LCPD) is uncommon in girls. The presentation of LCPD in female patients has been reported as later in onset and associated with certain high-impact activities. Our aim is to characterize the presentation of female LCPD at a large center, with particular attention to the clinical and radiographic features of late-onset disease (>ten years of age). We perceived an increasing burden of late-onset disease with adult-like radiographic features. METHODS:All patients presenting to a single large urban children's hospital from 1990-2014 with a diagnosis of LCPD were reviewed. Demographic, clinical, and radiographic data for all female patients were examined and compared to historical norms. RESULTS:Four-hundred and fifty-one patients presented with LCPD in the study period, of which 82 (18.2 %) were female. The average age at presentation was 6.58 years in girls, which is similar to the classically reported mean age. Fourteen patients participated in high-impact repetitive activities or those with deep flexion and abduction, although few were late presenters. There were four female patients who presented for initial diagnosis >ten years of age. CONCLUSIONS:There was a paucity of late-onset LCPD in girls in the study population, and the females with LCPD had a very similar age and character to their presentation as did males. Although their presentation is infrequent, three of four older females with LCPD were engaged in high-level physical activity, and their disease may be attributed to high-impact, repetitive athletics. LEVEL OF EVIDENCE:Case series, Level IV.
| S-EPMC4549350 | biostudies-other
Project description:BackgroundAbnormal development and growth of the capital femoral epiphysis and acetabulum are associated with a wide variety of underlying etiologies, one of which is Legg-Calvé-Perthes disease.Case descriptionWe report the cases of two children who presented with abnormal development of both hips and in whom novel mutations in the COL2A1 gene were found. These cases illustrate the importance of identifying individuals with a type II collagen abnormality, as it informs management, allows investigation for other complications, and provides the opportunity for accurate genetic counseling and consideration of other family members who might be at risk.Literature reviewThe literature documents numerous private mutations in COL2A1 associated with diverse clinical phenotypes including bilateral hip dysplasia and premature osteoarthritis. Some of these mutations are associated with a joint-specific phenotype but few other skeletal or extraskeletal manifestations. Only careful clinical examination of children presenting with hip anomalies therefore will reveal additional findings that warrant an evaluation by a clinical geneticist. DNA mutation analysis may be useful for making a specific diagnosis and identifying other at-risk family members.Purposes and clinical relevanceThe purpose of our report is to alert clinicians to the possibility that children who present with bilateral Perthes-like disease of the hip might have an underlying mutation in the gene encoding type II collagen. It is important to consider this in the differential diagnosis and workup of such children as it has specific prognostic, clinical, genetic counseling, and reproductive sequelae.
| S-EPMC3094608 | biostudies-literature