Features of musculoskeletal apparatus and bone tissue in patients with premature aging syndromes

Premature aging syndromes are a group of ultra-rare heterogeneous hereditary diseases that manifest predominantly in childhood and are characterized by accelerated aging of the organism. Despite differences in pathogenesis, the diseases are characterized by multisystem changes, including lesions of the musculoskeletal system, which are represented by multiple joint contractures, deformations of the spine and limbs, and changes in bone structure.

The examination data of 6 patients were analyzed: 5 children (3 boys and 2 girls) with pediatric progeria (Hutchinson-Gilford syndrome) (4 patients with classic genotype of pediatric progeria (c.1824 C>T in the LMNA gene) and 1 child with a non-classical (c.1968+1G>A in the LMNA gene)) and one girl with neonatal progeria (Wiedemann-Rautenstrauch syndrome) (c.3337- 11T>C/ c.3677T>C in the POLR3A gene). The diagnosis was made at the age of 1.9 (1.5; 4.3) years (Me (25%; 75%)). Patients were under the supervision of a pediatric endocrinologist, examined by an orthopedic traumatologist, radiologic studies, and densitometry of the lumbar spine were performed. The age at the time of the initial examination was 6.0 (3.5; 7.2) years, and at the time of the repeated examination — 7.6 (7.5; 9.3) years.

Bone and joint changes in Hutchinson-Gilford syndrome were represented by contractures of interphalangeal joints of fingers and toes, wrist, elbow, hip, knee, and ankle joints, and flat-valgus feet; in a patient with a nonclassical genotype of pediatric progeria, these changes were diagnosed at the first examination at 1 year 6 months of age, which confirms the severe course of the disease in this genotype. In 2 older patients (7 years 5 months and 9 years 10 months) coxa valga on 2 sides with development of aseptic necrosis of the femoral head and closed dislocation of the left femur were also diagnosed. In neonatal progeroid syndrome, musculoskeletal lesions were manifested as multiple contractures of large and small joints and spinal deformity. Bone age either corresponded to the chronologic age or lagged behind by 18 (15; 26) months All patients were diagnosed with osteoporosis according to densitometry (Z-criterion: -3.4 (-3.0; -3.8)); no fractures were recorded.

The revealed changes in bone tissue and musculoskeletal system in our patients correspond to the features described in the world literature in patients with Hutchinson-Gilford and Wiedemann-Rautenstrauch syndromes. The similarity of pathologic changes indicates the similarity of phenotypes of diseases included in the group of premature aging syndromes.

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