[Clinical and genetic characterisation of hereditary distal myopathies in a series of Colombian patients]. / Caracterización clínica y genética de miopatías distales hereditarias en una serie de pacientes colombianos.

INTRODUCTION: Hereditary distal myopathies represent a heterogeneous group of rare genetic disorders characterized by progressive distal muscle weakness. AIM: The objective of this study was to describe the clinical spectrum and genetic findings in a series of patients with distal myopathy from Colombia. PATIENTS AND METHODS: A retrospective review of the medical records of 12 patients with distal myopathy seen at a neuromuscular center in Bogota, Colombia, between 2015 and 2023 was performed. Clinical data, family history, diagnostic studies and genetic test results were obtained. RESULTS: The mean age of onset was 15.7 years. Patterns of limb weakness included distal involvement in the upper and lower extremities (50%), distal involvement in the lower extremities in isolation (33.3%), and proximal and distal involvement in the upper and lower extremities (8.3%). Additional weakness was observed in the face (8.3%) and paraspinal muscles (25.0%). Creatine kinase levels were elevated in 58.3% of cases. Electromyography revealed a myopathic pattern in 91.6% of cases. Variants identified included MYH7, ANO5, TTN, HNRNPA1, DES, DYSF and CAV3 genes. CONCLUSION: This case series describes the clinical and genetic spectrum of inherited distal myopathies in Colombia. Findings demonstrate phenotypic and genotypic heterogeneity, with variants in genes encoding structural proteins. There is a need to expand access to genetic testing in Latin America to enable more accurate comprehensive diagnosis and treatment.

TITLE: Caracterización clínica y genética de miopatías distales hereditarias en una serie de pacientes colombianos.Introducción. Las miopatías distales hereditarias son un grupo heterogéneo de trastornos genéticos raros caracterizados por debilidad muscular distal progresiva. Objetivo. Nuestro objetivo fue describir el espectro clínico y los hallazgos genéticos en una serie de pacientes con miopatía distal de Colombia. Pacientes y métodos. Se realizó una revisión retrospectiva de las historias clínicas de 12 pacientes con miopatía distal atendidos en un centro neuromuscular de Bogotá, Colombia, entre 2015 y 2023. Se obtuvieron datos clínicos, antecedentes familiares, estudios diagnósticos y resultados de pruebas genéticas. Resultados. La edad media de inicio fue de 15,7 años. Los patrones de debilidad de las extremidades incluyeron afectación distal en las extremidades superiores e inferiores (50%), distal en las extremidades inferiores de forma aislada (33,3%), y proximal y distal en las extremidades superiores e inferiores (8,3%). Se observó debilidad adicional en la cara (8,3%) y en los músculos paraespinales (25%). La creatincinasa estaba elevada en el 58,3%. El electromiograma mostró un patrón miopático en el 91,6%. Las variantes identificadas incluyeron los genes MYH7, ANO5, TTN, HNRNPA1, DES, DYSF y CAV3. Conclusiones. Esta serie de casos describe el espectro clínico y genético de las miopatías distales hereditarias en Colombia. Los hallazgos demuestran heterogeneidad fenotípica y genotípica, con variantes en genes que codifican proteínas estructurales. Es necesario ampliar el acceso a las pruebas genéticas en América Latina para permitir un diagnóstico y un tratamiento integral más precisos.

Phenotypic Spectrum of Myopathies with Recessive Anoctamin-5 Mutations.

BACKGROUND: Biallelic variants in Anoctamin 5 (ANO5) gene are causative of limb-girdle muscular dystrophy (LGMD) R12 anoctamin5-related, non-dysferlin Miyoshi-like distal myopathy (MMD3), and asymptomatic hyperCKemia. OBJECTIVE: To describe clinic, histologic, genetic and imaging features, of ANO5 mutated patients. METHODS: Five patients, four from France (P1, P2, P3 and P4) and one from Mexico (P5), from four families were included. P1 and P2, belonging to group 1, had normal muscle strength; Group 2, P3, P4 and P5, presented with muscular weakness. Muscle strength was measured by manual muscle testing, Medical Research Council (MRC) grades 1/5 to 5/5. Laboratory exams included serum CK levels, nerve conduction studies (NCS)/needle electromyography (EMG), pulmonary function tests, EKG and cardiac ultrasound. ANO5 molecular screening was performed with different approaches. RESULTS: Group 1 patients showed myalgias with hyperCKemia or isolated hyperCKemia. Group 2 patients presented with limb-girdle or proximo-distal muscular weakness. Serum CK levels ranged from 897 to 5000 UI/L. Muscle biopsy analysis in P4 and P5 showed subsarcolemmal mitochondrial aggregates. Electron microscopy confirmed mitochondrial proliferation and revealed discontinuity of the sarcolemmal membrane. Muscle MRI showed asymmetrical fibro-fatty substitution predominant in the lower limbs.P1 and P2 were compound heterozygous for c.191dupA (p.Asn64Lysfs*15) and c.1898 + G>A; P3 was homozygous for the c.692G>T. (p.Gly231Val); P4 harbored a novel biallelic homozygous exons 1-7 ANO5 gene deletion, and P5 was homozygous for a c.172 C > T (p.(Arg 58 Trp)) ANO5 pathogenic variant. CONCLUSIONS: Our cohort confirms the wide clinical variability and enlarge the genetic spectrum of ANO5-related myopathies.

Tumor de células gigantes da extremidade distal do fêmur: um desafio de tratamento / Giant cell tumor of femoral distal end: a challenge in treatment

Apresentamos aqui um caso de tumor de células gigantes na extremidade distal do fêmur direito tratado com ressecção da massa tumoral em bloco com remoção aguda da extremidade proximal e distal e fixado com hastes longas em K atravessando o joelho, do fêmur à tíbia. Após a consolidação / união completa das extremidades, foi feita a remoção da haste em K, seguida pela corticotomia juntamente com a osteogênese da distração com o auxílio do anel fixador de Ilizarov. O comprimento foi alcançado com este processo. O resultado final foi muito bom neste caso. Revisamos as opções de tratamento para tumor maligno de células gigantes na extremidade distal do fêmur e as dificuldades de tratá-lo.

We present a case of malignant giant cell tumor of distal end of right femur treated with resection of the tumor mass en block with acute docking of proximal and distal end and fixed with long K-nail across knee from femur to tibia. After complete consolidation/ union of the ends, removal of K nail was done followed by corticotomy along with distraction osteogenesis with the help of Ilizarov ring fixator. The length was achieved with this process. The end result was very good in this case. We reviewed the treatment options for malignant giant cell tumor of femoral distal end and the challenges in its treatment.