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.

Gradual ulnar lengthening in Masada type I/IIb deformity in patients with hereditary multiple osteochondromas: a retrospective study with a mean follow-up of 4.2 years.

BACKGROUND: Gradual ulnar lengthening is the most commonly used procedure in the treatment of Masada type I/II deformity in patients with hereditary multiple osteochondromas. However, the treatment remains controversial for the recurrence of deformity in growing children. This study aims to evaluate the clinical and radiological outcomes of ulnar gradual lengthening in our clinic. METHODS: We retrospectively reviewed patients who underwent ulnar lengthening by distraction osteogenesis from June 2008 to October 2017. The carrying angle (CA) and range of motion (ROM) of the forearm and elbow were clinically assessed, and the radial articular angle (RAA) and ulnar shortening (US) were radiologically assessed before lengthening, 2 months after external frame removal, and at the last follow-up. RESULTS: The current study included 15 patients (17 forearms) with a mean age of 9.4 ± 2.3 years at the index surgery. The mean follow-up period was 4.2 ± 2.4 years. There were 9 patients (10 forearms) with Masada type I deformity and 6 patients (7 forearms) with Masada type IIb deformity. The mean amount of ulnar lengthening was 4.2 ± 1.2 cm. The mean RAA improved from 37 ± 8 to 30 ± 7° initially (p = 0.005) and relapsed to 34 ± 8° at the last follow-up (p = 0.255). There was a minimal deterioration of US yet significant improvement at the last follow-up compared to pre-op (p < 0.001). At the last follow-up, the mean forearm pronation and elbow flexion increased significantly (p < 0.001 and p = 0.013, respectively), and the mean carrying angle also improved significantly (p < 0.001). No patient with type IIb deformity achieved a concentric radial head reduction. CONCLUSIONS: Gradual ulnar lengthening significantly reduces cosmetic deformity and improves function in patients with Masada type I/IIb deformity. Our results supported early ulnar lengthening for patients with a tendency of dislocation of the radial head.

Validation of a new multiple osteochondromas classification through Switching Neural Networks.

Multiple osteochondromas (MO), previously known as hereditary multiple exostoses (HME), is an autosomal dominant disease characterized by the formation of several benign cartilage-capped bone growth defined osteochondromas or exostoses. Various clinical classifications have been proposed but a consensus has not been reached. The aim of this study was to validate (using a machine learning approach) an "easy to use" tool to characterize MO patients in three classes according to the number of bone segments affected, the presence of skeletal deformities and/or functional limitations. The proposed classification has been validated (with a highly satisfactory mean accuracy) by analyzing 150 different variables on 289 MO patients through a Switching Neural Network approach (a novel classification technique capable of deriving models described by intelligible rules in if-then form). This approach allowed us to identify ankle valgism, Madelung deformity and limitation of the hip extra-rotation as "tags" of the three clinical classes. In conclusion, the proposed classification provides an efficient system to characterize this rare disease and is able to define homogeneous cohorts of patients to investigate MO pathogenesis.

[Genetic basis for skeletal disease. Genetic defects in chondrodysplasia].

Chondrodysplasia is a subset of skeletal dysplasia caused by genetic defects affecting chondrogenesis and its development, showing abnormal shape and structure of the skeleton. Pathology of growth plate results in defective skeletal development, such as short stature, while pathology of articular cartilage predisposes degenerative skeletal disease, such as early-onset osteoarthritis. Recently identified genetic basis for chondrodysplasia contributed much in understanding the biology and pathology of cartilage. The accumulated knowledge would be a clue to develop fundamental treatment for chondrodysplasia.

Characteristic factors of ankle valgus with multiple cartilaginous exostoses.

BACKGROUND: Ankle valgus is one of the most common deformities in multiple cartilaginous exostoses (MCEs). However, the characteristic factors of ankle valgus are not well known. METHODS: To determine the characteristic factors of ankle valgus in MCE, we investigated 62 ankles in 33 patients (23 males, 10 females) with no history of surgical treatment of ankles with MCE. Mean age at investigation was 11 years 4 months (range, 2 years 7 months-17 years 1 month). We evaluated Taniguchi classification, tibiotalar angle (ankle valgus), site of exostoses in the distal tibia and distal fibula, fibular shortening (Malhotra classification), and correlations between these factors. RESULTS: According to Taniguchi classification, patients were classified as group II (n = 8), group III (n = 18), or unknown (n = 7). Mean tibiotalar angle was 5.1 degrees (range, -4 to 20 degrees) in males and -0.8 degrees (range, -5 to 7 degrees) in females. Significant differences in ankle valgus were found between sexes within the same age group, and ankle valgus progressed with age in males. Ankles with involvement of both lateral distal tibia and medial distal fibula showed significantly more severe ankle valgus than ankles with involvement of the lateral distal tibia alone or no involvement. In Malhotra classification, all except 1 ankle showed station 0 in females. All cases of station II or III involved males and degree of fibular shortening correlated with ankle valgus in males. Taniguchi group III was associated with more frequent involvement of both lateral distal tibia and medial distal fibula in males, and greater frequency of both fibular shortening and ankle valgus with >or=10 degrees was seen compared with Taniguchi group II. CONCLUSIONS: Several characteristic factors of ankle valgus in MCE seem to predict progression.

Ulna/height ratio as clinical parameter separating EXT1 from EXT2 families?

Multiple osteochondromas (MO) is an autosomal-dominant inherited disorder. The two genes responsible (EXT1 and EXT2) have been identified. We investigated 12 MO families for phenotype details and the genetic basis by cosegregation and mutation analysis (seven novel pathogenic mutations [five frameshift, one splice site, and one gross deletion] and one novel missense polymorphism). We found EXT1 to be responsible in seven families (19 affected members) and EXT2 in four families (17 affected members). One family remains undetermined. We found a tendency to a more severe phenotype in EXT1 families. As a novel finding, we could identify a single parameter (ulna/height ratio) that separates EXT1 family from EXT2 family in our series.

Reconstruction of forearm deformities in multiple cartilaginous exostoses.

The management of complex forearm deformities in patients with multiple cartilaginous exostoses is controversial. The objective of this study is to look into the outcome of treatment with the combined use of ulna lengthening, radial osteotomy, and excision of exostosis in our six patients, who all had Masada type 1 deformity of the forearm. Clinical assessment was performed using the pre- and postoperative range of motion of the wrist, forearm and elbow. The chief symptom each patient had was noted as well as the demographic data of all patients. Radiological assessment was performed by checking the degree of negative ulna variance, the radial articular angle, and the degree of carpal slip. The degree of satisfaction of the patients and their parents were noted. Good clinical and radiological results were obtained at a mean follow-up of 2.5 years. All patients and parents were satisfied and there was no recurrence of deformity in the latest follow-up. The authors believe in early and aggressive treatment of Masada type 1 deformity of the wrist and forearm for multiple cartilaginous exostoses with a combination of excision of exostosis, ulna lengthening and radial osteotomy.

[The Taniguchi classification in cases of multiple cartilaginous exostoses]. / Klasyfikacja Taniguchi w przypadkach mnogich wyrosli chrzestno-kostnych.

27 patients treated surgically at Child Orthopaedic Clinic of Pomeranian Medical Academy between 1974-1996 for multiple cartilaginous exostosis (Aclasia Diaphysealis Keith) were classified into three groups according to the Taniguchi classification. This classification is based on whether multiple cartilaginous exostoses are present on distal forearm. Group I--no involvement of the distal forearm (n = 2), in group II involvement of the distal forearm without shortening of either bone (n = 7) was stated. Group III consists of members with involvement of the distal forearm with shortening the radius or the ulna (n = 18). Groups were compared with regard to: number of lesions, distribution of exostoses in different body areas, age of onset of the Keith disease, height of children, presence of valgus deformity of the ankle, dislocation of the radial head and presence of exostoses around hip area. This classification should be useful in estimating severity of Keith disease, identifying cases at high risk for complications like dislocation of the radial and malignant transformation.

Torus y exostósis óseas: revisión de la literatura / Torus and bony exostosis: review of the literature

Los torus o exostósis óseas se consideran excrecencias no neoplásicas, las cuales se localizan en los maxilares, provenientes del mismo hueso. Estas excrecencias óseas pueden clasificarse de acuerdo a su localización, forma, tamaño y número y cuyo tratamiento únicamente esta indicado cuando la estética y la planificación de una prótesis total o removible así lo requieren

Identification of mutation in a candidate gene for hereditary multiple exostoses type II.

OBJECTIVES: To identify possible mutations in our previously cloned candidate gene for hereditary multiple exostoses type II (EXT2) in affected members of EXT families so as to confirm that it is the disease-causing gene. METHODS: The mutation was detected first by single strand conformational polymorphism (SSCP) of all coding exons of the candidate gene and then by sequencing analysis. RESULTS: After analyzing 37 patients from 20 Chinese EXT families by SSCP and DNA sequencing analysis, one 2-bp insertion mutation was identified in this candidate gene in affected members of an EXT family. This mutation resulted in the frameshift and generated a truncated gene product consisting of 105 amino acids. CONCLUSIONS: The identification of the mutation in the candidate gene indicates that this novel gene is responsible for EXT2 (one of the disease-causing gene of EXT).

A practical classification system for multiple cartilaginous exostosis in children.

Forty-one patients with multiple cartilaginous exostosis (MCE) were classified into three groups: Group I, no involvement of the distal forearm (n = 8); Group II, involvement of the distal forearm without shortening of the radius or ulna (n = 11); Group III, involvement of the distal forearm with shortening of the radius or ulna (n = 22). Groups were compared with regard to number of lesions, regional morbidity rate, age of onset, height, and presence of valgus deformity of the ankle. From these results, children in Group I were mildly affected. Further, those in Group III were severely affected, and all children in Group III had lesions of the innominate bone or proximal femur, where secondary chondrosarcoma occurs most frequently. This classification should prove useful in estimating severity and identifying cases at high risk for malignant transformation. MCE seemed to be an aberrant enchondral ossification and its mode of development to be reflected in the growth potential of each bone. Dislocation of the radial head occurred in three cases and was the initial symptom in two of these. Dislocation of the radial head may occur earlier than previously thought, hindering its prevention.

A gene for hereditary multiple exostoses maps to chromosome 19p.

Hereditary multiple exostoses (EXT) is an autosomal dominant bony disorder characterized by the formation of cartilage-capped juxta-epiphyseal prominences on the long bones. Recently, a disease gene (EXT 1) has been mapped to chromosome 8q23-q24 by linkage analysis in informative families. Here, we report on the genetic mapping of a second locus (EXT 2) to the short arm of chromosome 19 by linkage to a microsatellite DNA marker at the D19S221 locus, which gives additional support to the view that EXT is a genetically heterogeneous condition.