The Rizzoli Multiple Osteochondromas Classification revised: describing the phenotype to improve clinical practice.

Multiple osteochondromas (MO) is a rare disorder, characterized by benign osteocartilaginous tumors (osteochondromas), arising from the perichondrium of bones. The osteochondromas increase during growth, frequently causing deformities and limitations. Our study aims to analyze the data captured by the Registry of Multiple Osteochondromas, to refine Istituto Ortopedico Rizzoli (IOR) Classification, providing a representative picture of the phenotypic manifestations throughout the lifespan. We conducted a single-institution cross-sectional study. Patients were categorized according to IOR Classification, which identifies three patients' classes on the presence/absence of deformities and/or limitations. The present dataset was compared with our previously published data, to refine the classification. Nine hundred sixty-eight patients were included: 243 children (<10 years), 136 adolescents (10-15 years), and 589 adults. Of the entire population, half patients presented at least one deformity, and one quarter reported at least one limitation. Compared with our previous study, the amount of children was more than doubled and the percentage of mild/moderate cases was notably increased, giving a better disease overview throughout the lifespan and suggesting a different cut-off for dividing Class II in subclasses. We confirmed that MO is characterized by phenotypic heterogeneity, suggesting that an early classification of the disease may offer a useful tool to follow disease pattern and evolution, to support clinical practice, and to propose timely interventions.

Osteochondromas: An Updated Review of Epidemiology, Pathogenesis, Clinical Presentation, Radiological Features and Treatment Options.

Osteochondroma, the most common benign bone tumor, is a projection on the external surface of the bone, which can be sessile or pedunculated. 85% of osteochondromas present as solitary lesions, while 15% occur in the context of hereditary multiple exostoses (HME), a genetic disorder that is inherited in an autosomal dominant manner. Although often asymptomatic, symptoms may eventuate from compression of adjacent vessels or nerves, fractures, osseous deformities, bursa formation, or malignant transformation. Cartilage cap thickness >2 cm in adults or >3 cm in children as well as new onset of pain or growth, or rapid growth of the lesion, especially after the closure of the growth plate, might reflect cancerous transformation. Surgical resection is indicated for symptomatic lesions, complications, cosmetic reasons or malignant transformation. Excision of the tumor with free margin is the treatment of choice. Local recurrence is less than 2% if complete resection is achieved.

Exostosis múltiple hereditaria presentación de caso / Multiple hereditary exostosis. Case report

RESUMEN La exostosis hereditaria múltiple es un trastorno autosómico dominante que se suele presentar en las dos primeras décadas de la vida. Caracterizada por el remodelado metafisaria alterado y crecimiento óseo asimétrico con acortamiento secundario de los huesos de las extremidades. Estas exostosis óseas rodeadas de cartílagos se hacen prominentes a las partes blandas, se diferencia de la enfermedad de Ollier en que esta última no es hereditaria. Se presentó el caso de una mujer de 36 años, que presentaba acortamiento de los miembros especialmente, cubito y radio, metacarpianos y metatarsianos. Su hijo de 18 años afectado también de dicha enfermedad presentaba una deformidad de Madelung asociada (acortamiento de cubito y radio con arqueamiento del radio) (AU).

ABSTRACT Multiple hereditary exostosis is an autosomal dominant disorder, usually found in the first two decades of life. It is characterized by the altered metaphyseal remodeling and asymmetric bone growth with a secondary shortening of extremities bones. These bone exostoses surrounded by cartilages become prominent to the soft parts, and are different from the Ollier disease because this last one is not hereditary. The authors present the case of a woman, aged 36 years, presenting a shortening of the members, especially ulna and radius, metacarpus and metatarsus. Her 18-years-old son was also affected by this disease, having an associated Madelug deformity (shortening of ulna and radius, and radius bowing) (AU).

Prospective spine at risk program for prevalence of intracanal spine lesions in pediatric hereditary multiple osteochondromas.

STUDY DESIGN: Retrospective cohort study OBJECTIVES: To determine prevalence of hereditary multiple osteochondromas (HMO) and utility of MRI surveillance in a prospective Spine at Risk (SAR) program. Unidentified intraspinal exostoses in HMO can lead to neurologic injury in children during sedated procedures but no MRI guidelines exist. We sought to determine the prevalence and age of intraspinal exostoses from MRIs, and indications for MRI surveillance. METHODS: Retrospective review was performed of pediatric HMO patients who underwent total spine MRIs at a single institution after a prospective SAR program was instituted. Charts were reviewed for MRI indication and findings, symptoms, surgery, and location of other exostoses. Fisher's exact test was used to compare categorical variables and T test to compare continuous variables. Predictive value of pelvic/rib exostoses was calculated for intraspinal lesions. RESULTS: Forty-three patients with HMO underwent total spine MRIs with average age of 11.5 years. Fifteen (35%) patients had exostoses on vertebral column, eight (19%) had intra-canal spinal exostoses. Higher prevalence of spine lesions occurred in symptomatic patients than asymptomatic (any spinal lesion: 73% prevalence in symptomatic vs 22% in asymptomatic, p < 0.005; intra-canal spinal lesion: 46% vs 9%, p < 0.05). Only two of the 11 'symptomatic presentations' could be attributable to intracanal spinal exostoses. Only one intra-canal exostosis found on asymptomatic surveillance was treated surgically. Presence of pelvic or rib exostoses were not strongly predictive of intra-canal lesions (23% PPV, 85% NPV, 63% sensitivity, 51% specificity). CONCLUSIONS: Even with the presence of intra-canal exostoses, true symptomatic lesions are rare. Rib and pelvic lesions were not predictive of intra-canal lesions in our population. We recommend obtaining MRIs at time of preoperative evaluation in asymptomatic children old enough to not need sedation, or in patients with true neurologic symptoms to prevent unnecessary sedation of younger children for surveillance MRI. LEVEL OF EVIDENCE: III.

Predicting Radial Head Instability in Multiple Hereditary Exostoses (MHE): A Multicenter Analysis of Risk Factors.

BACKGROUND: Forearm deformity occurs in one third of patients with multiple hereditary exostoses (MHE). Conservative and surgical treatment are aimed at preventing radial head subluxation and/or dislocation. Dislocation has been associated with isolated distal ulnar lesions, radial bowing, and ulnar shortening. Risk factors for radial head subluxation have not been clearly elucidated. This study aimed to identify risk factors for all radial head instability in MHE, to optimize early detection and prevent frank dislocation. METHODS: This multicenter retrospective case-control investigation included MHE patients with forearm lesions seen between 2000 and 2017 at 2 tertiary care children's hospitals. Demographic, clinical factors, radiographic measures, and surgical history were quantified. Comparisons were made between forearms that developed radial head instability versus those that remained stable and between those that progressed to radial head subluxation versus those that progressed to dislocation. RESULTS: This study included 171 forearms in 113 patients with MHE, who presented at a mean age of 8.0 years with a median follow-up time of 6.0 years. Nine forearms progressed to radial head subluxation (mean age: 10.2 y), and 24 forearms had radial head dislocation (mean age: 9.9 y). Five subluxations and 3 dislocations occurred despite preventative surgery. Initial radial bowing (7.2% vs. 8.5%, P=0.04), ulnar variance (-5.8% vs. 11.0%, P<0.001), and ulnar shortening (-2.5 vs. 9.1 mm, P=0.04) were predictive of radial head instability. Distal ulnar lesions and more severe ulnar variance (-5.8 vs. -10.6, P<0.001) and shortening (-2.5 vs. 13.2 mm, P=0.02) were associated with an increased risk of radial head subluxation. No significant differences were identified between forearms that progressed to subluxation versus those that progressed to dislocation. CONCLUSIONS: Distal ulnar lesions and radiographic measures can be used to determine the risk of radial head instability in MHE. Ulnar variance and shortening are early identifiable risk factors for radial head subluxation that can help guide monitoring and treatment. Radial bowing may be a late predictor of instability. LEVEL OF EVIDENCE: Level III-prognostic.

Exostosis múltiple hereditaria / Hereditary multiple exostoses

Introducción: la exostosis múltiple hereditaria u osteocondromatosis hereditaria es una enfermedad poco frecuente, de transmisión autosómica dominante. Se caracteriza por el crecimiento anómalo, especialmente en las metáfisis de los huesos largos, de osteocondromas benignos que pueden provocar acortamiento o deformidades óseas. Suele diagnosticarse en la primera década de vida.Objetivo: presentar un caso con exostosis múltiple hereditaria, de reporte infrecuente en la literatura, como hallazgo identificado por los médicos colaboradores cubanos en la República de Ecuador.Presentación del caso: escolar masculino de seis años de edad. Acudió a consulta, acompañado de su madre, por presentar un bulto en la mano derecha, con aumento progresivo de tamaño, doloroso y que le impide escribir. En el examen físico se comprobó la deformidad en la extremidad superior derecha, con aumento de volumen en la muñeca de consistencia pétrea que desplazaba la arteria radial. En la tomografía axial computarizada se observó proyección exostósica del tercio distal del radio y se confirmó el diagnóstico.Discusión: las deformidades del antebrazo inducidas por la enfermedad se pueden corregir quirúrgicamente con éxito. La posible recurrencia durante la etapa de crecimiento del niño hace aconsejable esperar hasta la proximidad de la madurez esquelética para realizar los procedimientos correctivos del antebrazo. Conclusiones: las posibles complicaciones óseas, los trastornos neurológicos y vasculares asociados y el riesgo de malignización son características a tener en cuenta por la comunidad médica por la importancia de su diagnóstico temprano con la corrección oportuna de las deformidades óseas que provoca(AU)

Introduction: hereditary multiple exostoses or hereditary osteochondromatosis is a rare disease with autosomal dominant transmission. It is characterized by abnormal growth, especially in the metaphysis of long bones, of benign osteochondromas that can cause shortening or bone deformities. It is usually diagnosed in the first decade of life.Objective: to present a case with hereditary multiple exostoses, of infrequent report in the literature, as a finding identified by the Cuban collaborating doctors in the Republic of Ecuador.Case presentation: male schoolchild of six years of age. He went to consultation, accompanied by his mother, for presenting a lump in his right hand, with a progressive increase in size, painful and that prevents him from writing. In the physical examination, the deformity in the right upper extremity was confirmed, with an increase in the volume of the wrist with a stony consistency that displaced the radial artery. In the computerized axial tomography, an exostoses projection of the distal third of the radius was observed and the diagnosis was confirmed.Discussion: forearm deformities induced by the disease can be successfully corrected surgically. The possible recurrence during the growth stage of the child makes it advisable to wait until the proximity of the skeletal maturity to carry out the corrective procedures of the forearm.Conclusions: possible bone complications, associated neurological and vascular disorders and the risk of malignancy are characteristics to be taken into account by the medical community because of the importance of early diagnosis with the timely correction of bone deformities that it causes(AU)

Radiographic Analysis of the Pediatric Hip Patients With Hereditary Multiple Exostoses (HME).

BACKGROUND: This study aimed to report the radiographic presentation of involved hips in children with hereditary multiple exostoses (HME). This included radiographic hip measurements, osteochondromas location, and relationship with hip subluxation. METHODS: Anteroposterior pelvis radiographs of children with HME, seen between 2003 and 2014, were retrospectively reviewed. Only patients who were skeletally immature at the first visit were included. One radiograph per patient per year was reviewed. Radiographs were examined for the presence of osteochondromas and their locations. Different parameters were evaluated: femoral neck-shaft angle, Reimer migration percentage (MP), Sharp acetabular angle, Wiberg angle, femoral head-neck ratio (coronal plane), and Shenton line. All measured radiographs were divided into 3 age groups:≤8,>8 and <13, and ≥13 years. Differences of the measured parameters with age were evaluated. Children with hip subluxation were identified and any relationship with osteochondromas locations, as well as MP changes over time, was recorded. Radiographs of children with a minimum 2-year follow-up were identified and changes of their hip measurements and osteochondromas' presence over time were recorded. RESULTS: A total of 51 children (102 hips) with HME were identified. In most locations, there was an overall increase of the occurrence of osteochondromas in the older age groups. However, in the medial femoral neck, a significantly less numbers of osteochondromas were found after 13 years of age (P=0.018). There was a decrease in MP with age (P<0.05). There was also an increase in Sharp and Wiberg angles in the older patients (P<0.05). Hips with broken Shenton line decreased in number with age (P 0.028). Hip subluxation was encountered in 23 hips. No specific location of osteochondromas was found to have a relationship with subluxation. Thirty-six children had a minimum follow-up of 2 years (mean age at first visit 8.5 y and at last visit 13.1 y). In these children, an increased occurrence of lesions was found in medial femoral neck and ischium (P<0.05) between the first and the last visit. CONCLUSIONS: In children with HME, radiographic evaluation of the hip is necessary based on the high percentage of hip involvement. When hip osteochondromas are found, radiographic surveillance is recommended to detect hip subluxation. Surgery may certainly be necessary for symptomatic osteochondromas. However, given the possibility of improvement in hip parameters with age, early surgical treatment to improve hip longevity does not seem to be warranted. LEVEL OF EVIDENCE: Level IV-prognostic study.

The impact of hereditary multiple exostoses on quality of life, satisfaction, global health status, and pain.

PURPOSE: The aim of the study was to evaluate quality of life (QOL), global health status, pain, and level of satisfaction in patients with hereditary multiple exostoses (HME), and to correlate the association between the severity of diseases and age, sex, number of surgical procedures, and number of exostoses. METHODS: The data of 50 patients with HME were retrospectively evaluated and recorded. QOL was evaluated with the Short-Form Health Survey (SF-12) questionnaire, the 12-Item General Health Questionnaire (GHQ-12), and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF); intensity of pain was measured using the visual analogue scale (VAS). The association of age, gender, pain, quality of life, number of exostoses, and number of surgical procedures were evaluated and correlated. RESULTS: Mean number of exostoses in our patient's cohort resulted 18.12 ± 8.60, and every patient underwent to a mean of 5.62 ± 5.74 surgical procedures for the exostoses. Mean VAS resulted 5.16 ± 2.90. Considering SF-12, mental (MCS) and physical (PCS) component resulted, respectively, 45.36 ± 10.76 and 38.73 ± 11.09, while GHQ-12 and Q-LES-Q-SF were 15.48 ± 4.70 and 45.28 ± 9.55, respectively. We found a significant positive correlation between the number of exostoses and the number of surgical procedures (p < 0.001), a significant positive correlation between the number of surgical procedures and GHQ-12 (p = 0.422) and VAS (p = 0.0011), and a negative correlation between the number of surgical procedures and PCS (p = 0.0257) and between age and GHQ-12 (p = 0.0385). CONCLUSIONS: We can conclude that HME impact on patient quality of life as measured by the MCS and PCS scores similar to the disability associated with osteoarthritis in the mental component and tumors or diabetes as regards the physical component. Moreover, we found no difference in patients' quality of life as regards number of exostoses, age, and surgical procedure, but we found that women have a worse response as regards the psychological side than men.

Assessing the general population frequency of rare coding variants in the EXT1 and EXT2 genes previously implicated in hereditary multiple exostoses.

Hereditary multiple exostoses (HME) is a rare childhood-onset skeletal disease linked to mutations in exostosin glycosyltransferase 1 (EXT1) or 2 (EXT2). Patients are heterozygous for either an EXT1 or EXT2 mutation, and it is widely assumed that exostosis formation and associated defects, such as growth retardation and skeletal deformities, require loss-of-heterozygosity or a second hit in affected cells. However, the relevance and phenotypic impact of many presumed pathogenic EXT variants remain uncertain. We extracted all amino acid-altering (missense) and loss of function (LoF; nonsense, frameshift, or splice-site) variants from the Exome Aggregation Consortium (ExAC), a large population-based repository of exome sequence data from diverse ancestries that has screened out severe pediatric disease, to assess the overall mutation spectrum of predicted protein-damaging variants across these two genes in the general population. We then determined whether clinically-identified, presumably pathogenic variants implicated in HME exist among healthy individuals. We found six EXT1 and four EXT2 missense mutations in ExAC, suggesting that these mutations have either been misclassified as pathogenic or are not fully penetrant. Furthermore, EXT1 is heavily selectively constrained, while EXT2 is more tolerant to protein-damaging variants, especially at its C-terminus, possibly explaining the genotype-phenotype correlation that EXT1 variants usually result in more severe disease. In conclusion, population-based exome data is a useful filter for determining whether clinically detected variants are likely pathogenic, as well as revealing biological insight into rare disease genes such as EXT1 and EXT2.

Is hip dysplasia a common deformity in skeletally mature patients with hereditary multiple exostoses?

BACKGROUND: Various deformities appear in hereditary multiple exostoses (HMEs). Deformities around the knee or ankle joints are easy to detect in this disease because such deformities are visible in appearance. However, deformities in the hip joints of skeletally mature patients are not well understood because their tumors are invisible. METHODS: To understand deformities around the hip joint in HMEs, we investigated 36 hip joints in 19 skeletally mature patients (12 males, 7 females). The mean age at last X-ray imaging investigation was 29.2 years (14.5-66.5 years). We evaluated the lesions of exostoses around the acetabulum and proximal femur, Wiberg's center-edge angle (CEA), neck-shaft angle (NSA), acetabular depth-width ratio (ADR), and Sharp's acetabular angle. RESULTS: No exostoses were present in four hips of three cases. Thirty-one hip joints had exostoses on the medial side of the femoral neck. Exostoses existed on the lateral side of the femoral neck in 16 hips. None of the patients had acetabuluar tumors. One patient experienced pain because of impingement between the acetabular rim and medial tumors of the femoral neck. The increase in NSA, which is an index of proximal femoral deformity, was common with a mean NSA of 147.3 °. Two indices of acetabular deformity, Sharp's angle and ADR, were within normal limits with a mean Sharp's angle of 41.3 ° and mean ADR of 269. The average CEA was 29.9 °. CONCLUSIONS: Hip dysplasia is not necessarily common in skeletally mature patients with HMEs. To determine the possibility of hip dysplasia in skeletally immature patients with HMEs, ADR may be a useful reference index.

Multiple Hereditary Exostoses.

Multiple hereditary exostoses (MHE), also known as multiple osteochondromas, is an autosomal dominant disease that results in the development of osteochondromas throughout the body. The disease typically is diagnosed during childhood and requires lifelong monitoring and treatment of painful osteochondromas. Individuals with MHE must be monitored for complications that can arise and the potential malignant transformation of an osteochondroma into a chondrosarcoma. This article discusses the basic characteristics of MHE, genetic links, the role of medical imaging in diagnosis, and treatment options.

Exostosis múltiple hereditaria: reporte de una familia / Hereditary multiple exostoses: report of a family

FUNDAMENTO: el osteocondroma es el tumor óseo benigno frecuente en la edad pediátrica y la exostosis múltiple hereditaria en sus variedades, con un patrón de herencia autosómica dominante, con distribución simétrica por casi todo el esqueleto, aunque puede existir distribución asimétrica en dos de los tres genotipos de la enfermedad. OBJETIVO: presentar una familia portadora de exostosis múltiple hereditaria, diagnosticada de forma multidisciplinaria, por aspectos clínicos, radiológicos e histopatológicos. CASO CLINICO: se presenta un caso de una familia con malformaciones músculos esqueléticos. Predominó la estatura baja y las lesiones nodulares duras no dolorosas en brazos, antebrazos, muslos, piernas, costillas y escápulas, con deformidades en regiones proximales y distales en ambos brazos, antebrazos; así como en tercio proximal y distal de las piernas. En las radiografías se observaron lesiones en la diáfisis de los huesos afectados de diferentes aspectos, ovaladas, lobuladas y alargadas, las cuales están bien delimitadas. A todos los pacientes se les realizó exámenes de laboratorio, los cuales fueron normales y recibieron tratamiento quirúrgico con resección de las tumoraciones más prominentes y las que presentaron mayor tendencia a la malignización, como son las de las costillas, escápula, pelvis y hombros. CONCLUSIONES: la exostosis múltiple hereditaria se considera una enfermedad poco frecuente en nuestro medio y el tratamiento de elección es el quirúrgico para mejorar las manifestaciones clínicas.

BACKGROUND: osteochondroma is the most common benign osseous tumor in pediatric age and hereditary multiple exostoses is one of its types with a pattern of dominant autosomal heredity and a symmetrical distribution in almost all the skeleton, although an asymmetrical distribution can appear in two of the three genotypes of the disease. OBJECTVE: to present the case of a family that suffers from hereditary multiple exostoses diagnosed in a multidisciplinary way from clinical, radiological, and histopathological aspects. CLINICAL CASE: the case of a family with muscular-skeletal malformations is presented. Short height predominated, as well as non-painful hard nodular lesions in arms, forearms, thighs, legs, ribs, and scapulas with deformities in proximal and distal areas in both arms and forearms and in the proximal and distal third of the legs. From the radiological point of view, lesions of different aspects (oval, lobate, elongated) and of well-defined appearance were observed in the diaphysis of the affected bones. All the patients underwent laboratory exams, the results of which were normal. The patients underwent surgical treatment with removal of the most prominent tumors and mainly those which presented a greater tendency to become malignant, like rib, scapula, pelvis and shoulder. CONCLUSIONS: hereditary multiple exostoses constitute an infrequent illness in our environment and surgical treatment is the best choice to improve the clinical manifestations.

Scoliosis in patients with multiple hereditary exostoses.

PURPOSE: To investigate the prevalence of and to identify independent predictors associated with scoliosis in patients with multiple hereditary exostoses (MHE). METHODS: Fifty patients with MHE were clinically examined, and the diagnosis of scoliosis was made based on radiographs. To classify disease severity, three classes based on the presence of deformities and functional limitations were defined. Significant independent predictors of scoliosis in MHE were statistically analyzed. RESULTS: Scoliosis was present in 36 patients (MHE-scoliosis) (72 %). In the MHE-scoliosis group, the mean primary curve was 15.3° ± 5.7° (range 10°-34°) and the mean minor curve was 10.6° ± 7° (range 6°-32°). Left curve was predominant (72 %), and the apex was located in the thoracolumbar or lumbar spine in 64 % of patients. Univariable and multivariable analyses confirmed that MHE severity was a significant predictor of moderate scoliosis (≥20°). CONCLUSIONS: Our study confirmed that scoliosis is a common feature of MHE and disease severity is a predictor of moderate scoliosis (≥20°).

Exostosis múltiple hereditaria: reporte de una familia / Hereditary multiple exostoses: report of a family

Fundamento: el osteocondroma es el tumor óseo benigno frecuente en la edad pediátrica y la exostosis múltiple hereditaria en sus variedades, con un patrón de herencia autosómica dominante, con distribución simétrica por casi todo el esqueleto, aunque puede existir distribución asimétrica en dos de los tres genotipos de la enfermedad.Objetivo: presentar una familia portadora de exostosis múltiple hereditaria, diagnosticada de forma multidisciplinaria, por aspectos clínicos, radiológicos e histopatológicos.Caso clínico: se presenta un caso de una familia con malformaciones músculos esqueléticos. Predominó la estatura baja y las lesiones nodulares duras no dolorosas en brazos, antebrazos, muslos, piernas, costillas y escápulas, con deformidades en regiones proximales y distales en ambos brazos, antebrazos; así como en tercio proximal y distal de las piernas. En las radiografías se observaron lesiones en la diáfisis de los huesos afectados de diferentes aspectos, ovaladas, lobuladas y alargadas, las cuales están bien delimitadas. A todos los pacientes se les realizó exámenes de laboratorio, los cuales fueron normales y recibieron tratamiento quirúrgico con resección de las tumoraciones más prominentes y las que presentaron mayor tendencia a la malignización, como son las de las costillas, escápula, pelvis y hombros.Conclusiones: la exostosis múltiple hereditaria se considera una enfermedad poco frecuente en nuestro medio y el tratamiento de elección es el quirúrgico para mejorar las manifestaciones clínicas(AU)

Background: osteochondroma is the most common benign osseous tumor in pediatric age and hereditary multiple exostoses is one of its types with a pattern of dominant autosomal heredity and a symmetrical distribution in almost all the skeleton, although an asymmetrical distribution can appear in two of the three genotypes of the disease.Objective: to present the case of a family that suffers from hereditary multiple exostoses diagnosed in a multidisciplinary way from clinical, radiological, and histopathological aspects.Clinical case: the case of a family with muscular-skeletal malformations is presented. Short height predominated, as well as non-painful hard nodular lesions in arms, forearms, thighs, legs, ribs, and scapulas with deformities in proximal and distal areas in both arms and forearms and in the proximal and distal third of the legs. From the radiological point of view, lesions of different aspects (oval, lobate, elongated) and of well-defined appearance were observed in the diaphysis of the affected bones. All the patients underwent laboratory exams, the results of which were normal. The patients underwent surgical treatment with removal of the most prominent tumors and mainly those which presented a greater tendency to become malignant, like rib, scapula, pelvis and shoulder.Conclusions: hereditary multiple exostoses constitute an infrequent illness in our environment and surgical treatment is the best choice to improve the clinical manifestations(AU)

Skeletal growth patterns in hereditary multiple exostoses: a natural history.

Hereditary multiple exostoses (HME) is a commonly inherited musculoskeletal condition and is associated with a diminished stature. We demonstrated that adults with HME were significantly shorter when compared with a control group (P<0.001); preadolescents, however, were significantly taller than predicted (P=0.01). This was reflected by their height centile; 58% of the adults were under the 25th centile, whereas 53% of the preadolescence group were above the 75th centile. Stature was more severely affected in patients with an EXT1 mutation (P=0.008). This study illustrates a novel age-related growth pattern associated with HME, which is also affected by genotype.

Of brain and bone: the unusual case of Dr. A.

Frontotemporal dementia (FTD) is a clinical syndrome characterized by progressive decline in social conduct and a focal pattern of frontal and temporal lobe damage. Its biological basis is still poorly understood but the focality of the brain degeneration provides a powerful model to study the cognitive and anatomical basis of social cognition. Here, we present Dr. A, a patient with a rare hereditary bone disease (hereditary multiple exostoses) and FTD (pathologically characterized as Pick's disease), who presented with a profound behavioral disturbance characterized by acquired sociopathy. We conducted a detailed genetic, pathological, neuroimaging and cognitive study, including a battery of tests designed to investigate Dr. A's abilities to understand emotional cues and to infer mental states and intentions to others (theory of mind). Dr. A's genetic profile suggests the possibility that a mutation causing hereditary multiple exostoses, Ext2, may play a role in the pattern of neurodegeneration in frontotemporal dementia since knockout mice deficient in the Ext gene family member, Ext1, show severe CNS defects including loss of olfactory bulbs and abnormally small cerebral cortex. Dr. A showed significant impairment in emotion comprehension, second order theory of mind, attribution of intentions, and empathy despite preserved general cognitive abilities. Voxel-based morphometry on structural MRI images showed significant atrophy in the medial and right orbital frontal and anterior temporal regions with sparing of dorsolateral frontal cortex. This case demonstrates that social and emotional dysfunction in FTD can be dissociated from preserved performance on classic executive functioning tasks. The specific pattern of anatomical damage shown by VBM emphasizes the importance of the network including the superior medial frontal gyrus as well as temporal polar areas, in regulation of social cognition and theory of mind. This case provides new evidence regarding the neural basis of social cognition and suggests a possible genetic link between bone disease and FTD.

An extended outbreak of congenital chondrodysplasia in calves in South East Australia.

OBJECTIVE: To report an outbreak of congenital chondrodystrophy in calves in South East Australia. METHODS: District veterinarians investigated reported cases of calf deformities. Owners of affected herds were interviewed using a standard questionnaire to identify potential risk factors. Dams of several affected calves were serologically tested for Akabane virus, Aino virus, pestivirus and bluetongue, and affected calves were tested for pestivirus antigen and serum immunoglobulin concentrations. Gross and histopathological examinations of numerous calves were performed, concentrating on the musculoskeletal system. RESULTS: A case definition of distinctive skeletal deformities was established, and 89 property owners reported calves with chondrodystrophy in Spring 2003, 2004 or 2005. Some 14 property owners reported affected calves in more than one year. Prevalence and severity of deformity varied greatly between and within properties. None of breed, sex, age of dam, lineage, pasture type, supplementary feeding, fertiliser use or toxic plants was consistently associated with the disease. All dams experienced hot, dry conditions during the first trimester of pregnancy and were exposed to adverse conditions thereafter. Consistently dams were reported to have been grazing undulating to hilly terrain during early pregnancy. All serological tests were negative for Akabane virus, Aino virus, pestivirus and bluetongue. Histopathology of affected skeletal samples showed chondrodysplasia. CONCLUSION: The outbreak had similarities with previous outbreaks reported in the region. No specific aetiology could be determined. There is some evidence that the cause of the deformities could be a manganese deficiency during foetal development. Ongoing work to test this hypothesis is therefore warranted.

Inherited chondrodysplasia in Texel sheep.

CASE HISTORY: A skeletal disease characterised by dwarfism, limb deformity and sometimes sudden death occurred over a period of 5 years in lambs born on a commercial sheep farm in Southland. The disease showed variable expression and occurred in crossbred sheep. A genetic aetiology was supported by the birth of affected lambs over two seasons in a flock of putative carrier and affected sheep transported to Massey University. CLINICAL FINDINGS: Affected lambs appeared normal at birth but showed evidence of dwarfism, wide-based stance and exercise intolerance as early as 1 week of age. Most died within the first 3 months of life, often after developing bilateral varus deformity of the forelimbs. Some severely-affected lambs died suddenly of respiratory embarrassment, probably due to tracheal collapse. Mildly-affected individuals had a short, blocky stature and some survived to breeding age. PATHOLOGICAL FINDINGS: Gross and microscopic lesions of variable severity were present in the tracheal, articular, epiphyseal and physeal cartilages. In severe cases, articular cartilage in major joints was eroded from weight-bearing surfaces. The trachea was flaccid, abnormally kinked, and had thickened cartilaginous rings and a narrow lumen. Affected sheep that survived to breeding age eventually developed severe degenerative joint disease. Histologically, chondrocytes were disorganised, surrounded by concentric rings of abnormal fibrillar material, and the matrix often contained focal to coalescing areas of chondrolysis. DIAGNOSIS: Inherited chondrodysplasia of Texel sheep. CLINICAL RELEVANCE AND CONCLUSIONS: This chondrodysplasia differs from those previously described in sheep and is considered to be a newly-recognised, recessively-inherited genetic disease of the Texel breed. A defect in the synthesis of glycosaminoglycans in cartilage matrix is suspected. This disease of sheep may provide a suitable model for studying various forms of therapy for human chondrodysplasias.

Natural history of multiple hereditary osteochondromatosis of the lower extremity and ankle.

In this study the authors evaluated the natural history of the ankle joint in patients with multiple hereditary osteochondromatosis. Thirty-eight subjects with an average age of 42 years completed a detailed subjective questionnaire and underwent clinical and radiographic evaluation of their ankles. Three subjects (8%) indicated their ankle involvement affected their vocation, and 12 (32%) were limited in recreational sports. Seven patients (18%) had pain in at least one ankle on a weekly basis, with an average ankle pain score of 2.2. Ankle range of motion averaged 50 degrees and subtalar motion was considered normal in two thirds of ankles. Radiographic evaluation documented an average tibiotalar tilt of 9 degrees of ankle valgus, with evidence of degenerative joint disease noted in 14 ankles (19%). Those with arthritic changes had significantly more tibiotalar tilt and diminished ankle range of motion compared with those without radiographic signs of osteoarthritis. These findings document measurable decreases in ankle function and suggest that correction or prevention of excessive tibiotalar tilt may be warranted to improve outcome.