Radiological characteristics of skeletal growth in neonates and infants with achondroplasia.

Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH.

Novel and recurrent COMP gene variants in five Japanese patients with pseudoachondroplasia: skeletal changes from the neonatal to infantile periods.

Pseudoachondroplasia (PSACH) is an autosomal dominant skeletal dysplasia caused by pathogenic variants of cartilage oligomeric matrix protein (COMP). Clinical symptoms of PSACH are characterized by growth disturbances after the first year of life. These disturbances lead to severe short stature with short limbs, brachydactyly, scoliosis, joint laxity, joint pain since childhood, and a normal face. Epimetaphyseal dysplasia, shortened long bones, and short metacarpals and phalanges are common findings on radiological examination. Additionally, anterior tonguing of the vertebral bodies in the lateral view is an important finding in childhood because it is specific to PSACH and normalizes with age. Here, we report five Japanese patients with PSACH, with one recurrent (p.Cys351Tyr) and four novel heterozygous pathogenic COMP variants (p.Asp437Tyr, p.Asp446Gly, p.Asp507Tyr, and p.Asp518Val). These five pathogenic variants were located in the calcium-binding type 3 (T3) repeats. In four of the novel variants, the affected amino acid was aspartic acid, which is abundant in each of the eight T3 repeats. We describe the radiological findings of these five patients. We also retrospectively analyzed the sequential changes in the vertebral body and epimetaphysis of the long bones from the neonatal to infantile periods in a patient with PSACH and congenital heart disease.