Multiple osteochondromatosis (MO), or EXT1/EXT2-CDG, is an autosomal dominant O-linked glycosylation disorder characterized by the formation of multiple cartilage-capped tumors (osteochondromas). In contrast, solitary osteochondroma (SO) is a non-hereditary condition. EXT1 and EXT2, are tumor suppressor genes that encode glycosyltransferases involved in heparan sulfate elongation. We present the clinical and molecular analysis of 33 unrelated Latin American patients (27 MO and 6 SO). Sixty-three percent of all MO cases presented severe phenotype and two malignant transformations to chondrosarcoma (7%). We found the mutant allele in 78% of MO patients. Ten mutations were novel. The disease-causing mutations remained unknown in 22% of the MO patients and in all SO patients. No second mutational hit was detected in the DNA of the secondary chondrosarcoma from a patient who carried a nonsense EXT1 mutation. Neither EXT1 nor EXT2 protein could be detected in this sample. This is the first Latin American research program on EXT1/EXT2-CDG.

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Multiple Osteochondromatosis (MO, MIM 133700 & 133701), an autosomal dominant O-glycosylation disorder (EXT1/EXT2-CDG), can be associated with a reduction in skeletal growth, bony deformity, restricted joint motion, shortened stature and pathogenic variants in two tumor suppressor genes, EXT1 and EXT2. In this work, we report a cross-sectional study including 35 index patients and 20 affected family members. Clinical phenotyping of all 55 affected cases was obtained, but genetic studies were performed only in 35 indexes. Of these, a total of 40% (n = 14) had a family history of MO. Clinical severity scores were class I in 34% (n:18), class II in 24.5% (n:13) and class III in 41.5% (n:22). Pathogenic variants were identified in 83% (29/35) probands. We detected 18 (62%) in EXT1 and 11 (38%) in EXT2. Patients with EXT1 variants showed a height z-score of 1.03 SD lower than those with EXT2 variants and greater clinical severity (II–III vs. I). Interestingly, three patients showed intellectual impairment, two patients showed a dual diagnosis, one Turner Syndrome and one hypochondroplasia. This study improves knowledge of MO, reporting new pathogenic variants and forwarding the worldwide collaboration necessary to promote the inclusion of patients into future biologically based therapeutics.

Introducción: La enfermedad por coronavirus se expandió rápidamente, esto llevó a un aumento de la demanda de los servicios sanitarios, por lo cual fue necesario adaptarse de manera acorde. Nuestro objetivo es proporcionar una visión general del impacto en la atención y de nuestra experiencia, identificar aspectos positivos y aquellos por mejorar para futuras planificaciones. Materiales y Métodos: Se registraron el número de consultas diarias, la edad, el sexo, la presencia de traumatismo, el lugar de la lesión, el motivo de consulta, el diagnóstico y el tratamiento. Se comparó la cantidad de atenciones con las flexibilizaciones y con igual período de 2019. Resultados: Se realizaron 120 consultas, 33 procedimientos quirúrgicos, 185 atenciones por guardia, 160 con traumatismo. El lugar más frecuente de traumatismo fue el domicilio (56,25%). El 30% eran fracturas de muñeca y el 28,8%, supracondíleas. Las consultas aumentaron con las flexibilizaciones del confinamiento. Conclusiones: Es fundamental adaptarse rápido teniendo en cuenta que las fracturas comunes seguirán ocurriendo, pese al confinamiento al igual que las infecciones osteoarticulares. No descuidar tampoco la enfermedad crónica impostergable. Nivel de Evidencia: III