Impact of pediatric hematopoietic stem-cell transplantation on craniofacial growth

OBJECTIVES: To assess the craniofacial skeletal growth in pediatric hematopoietic stem-cell transplantation (HSCT) survivors in comparison with age-sex matched-paired controls. METHODS: A case-controlled retrospective comparison of the craniofacial growth in 25 HSCT children and 25 matched-paired controls was conducted. Craniofacial growth was quantitatively assessed by linear and angular measurements in panoramic radiographic images using ImageJ¯. Stature growth and body weight were obtained through physical examination. Cancer diagnosis, myeloablative conditioning, and HSCT were retrieved from medical records. RESULTS: Patients aged 12.2 years (±3.8; 16 male, 9 female). Radiographic images were obtained on an average of 2.43 (±2.0) years after HSCT. The main malignant diagnosis was acute lymphoblastic leukemia (56%), followed by acute myeloid leukemia (36%) and myelodysplastic syndromes (8%). Total body irradiation was associated with chemotherapy at 80%. Mean age at transplantation was 10 (±4.7) years. HSCT survivors showed reduced a vertical growth of the mandibular ramus (p=0.003). This persisted among individuals below 12 years of age (p=0.017). The HSCT group showed delayed dental eruption, though there was no statistically significant difference (p=0.3668). The HSCT group showed stature deficit, increased weight, and body mass index (Z-score stature: -0.28; Z-score weight: 0.38, respectively). CONCLUSIONS: Pediatric HSCT has decreased vertical craniofacial growth compared to their matched controls. There might be an association between reduced craniofacial vertical growth and reduced estature growth. Further studies to quantitatively investigate the impact of different myeloablative regimens in craniofacial skeletal growth and development.

Marshall-Smith Syndrome: Case Report

Marshall-Smith syndrome is a rare disease, with about 29 cases reported to date. It is characterized by accelerated bony growth and maturation, phalangeal abnormalities (wide middle and narrow distal phalanges), unusual facial features (prominent eyes, bluish sclerae, coarse eyebrows, an upturned nose, hypoplastic facial bones, and shallow orbits), failure to thrive, respiratory difficulties, and psychomotor retardation. This report of the radiologic findings of Marshall-Smith syndrome is, as for as we know, the first to be published in Korea.

MR Imaging of Growth Plate Injury in Rabbit: Development of Bony Bridge and Pathologic Correlation

PURPOSE: To evaluate the MR findings of a development of bony bridge within tunnels drilled across growth plates after injury in immature rabbits, and to correlate the MR and pathological findings. MATERIALS AND METHODS: In 19 young rabbits, a growth-plate injury model was constructed in the distal femur by longitudinal drilling with a 5-mm drill. Coronal scans with T1-weighted, T2-weighted fast spin-echo, gradient echo, and gadolinium enhanced T1-weighted sequences were obtained immediately, and at 1, 2, 3, and 4 weeks, and 3, 6 months, postoperatively. Each group underwent pathologic examination, and the signal intensity, shape, and enhancement pattern of the drill holes were assessed. All results were correlated with pathologic findings. RESULTS: During the early period, the signal intensity of the defect site varied due to hemorrhage and inflammatory reaction in the lesion, becoming isointense to that of metaphyseal marrow on all sequences during the late period (3 and 6 months). Pathologically, it corresponded to replacement of the osseous bridge with fatty marrow. The new bone formation shown by pathologic examination to be present in the periphery of the defect during the first week corresponded to the vertical dark rim seen on MR images. It appeared during that week and became more distinct, thickening gradually until the fourth week. Enhancement was absent or faint on follow-up immediately after surgery, inhomogenous and seen in half the rabbits at week 1, and maximal and homogenous at weeks 2 and 3. In had decreased by week 4, and was absent at months 3 and 6. These findings corresponded to the changes in transphyseal vascularity across the drill hole revealed by pathologic examination. CONCLUSION: The contrast enhancement demonstrated by defective growth plate may indicate the development of vascularity throughout the plate, a phenomenon which precedes the formation of a bony bridge after trauma.

The Normal Development of Proximal Humeral Epiphyseal Ossification Center in the First 2 Years of Life

PURPOSE: To ascertain the normal maturation of proximal epiphyseal ossification centers by monthly age duringthe first two years of life. MATERIALS AND METHODS: The distribution of age was 0 to 24 months. Six hundred andseventy-five infants were male and 436 were female;their ages were measured in months, and there was no evidenceof developmental problems. Proximal humeral epiphyseal ossification centers were evaluated from chestradiographs;if not visualized, they were graded as 0, and otherwise, as follows:Grade 1:visualized with poormargin or a diameter of less than 1/4 of metaphyseal width; Grade 2: visualized with good margin or a diameter ofmore than 1/4 of metaphyseal width;in grades 3 and 4, two ossification centers were visualized. Grade 3 indicatedthat one ossification center had the morphology of grade 2 and the other of grade 1, while in grade 4, bothossification centers were morphologically grade 2. Grade 5 indicated that two ossification centers were fused. Wethen assessed the relationship between the development of an ossification center and monthly age. RESULTS: Inmale children, modes were as follows:0 month, 0;1 month, 0 and 1;2-4 months, 1;5 months, 2;6 months, 1; 7-12months, 2;13-16 months, 3;17 months, 4;18 months, 2;19 months, 3 and 4;20-21 months, 4;22 months, 2 and 3; and23-24 months, 4. In female children, they were as follows:0 month, 0; 1-3 months, 1; 4 months, 2;5 months, 3;6months, 1; 7 months, 4;8 months, 3;9 months, 3 and 4;10 months, 4;11 months, 3;and 12-24 months, 4. In malechildren, mean ages were as follows:grade 0, 0.7 months; grade 1, 3.5 months;grade 2, 10.2 months;grade 3, 14.4months; grade 4, 18.1 months; and grade 5, 24 months. In female children, these means were as follows: grade 0,0.3 months; grade 1, 2.7 months; grade 2, 7 months; grade 3, 10.1 months; grade 4, 15 months; and grade 5, 20.8months. CONCLUSION: A proximal humeral epiphyseal ossification center shows regular maturational featuresaccording to monthly age.

Bone Changes in Phenylketonuria

PURPOSE: While treating 14 phenylketonuria(PKU) patients, we evaluated bone density, changes in bone age, andbony changes such as spiculation or metaphyseal widening. MATERIALS AND METHODS: A total of 14 PKU patients agedbetween 1 month and 14 years(mean, 6.4 years) were under dietary treatment. Eight and eleven patients underwentradiography of the left hand and wrist and bone densitometry(BMD) of the lumbar spine, respectively. The resultswere reviewed with regard to abnormal bony changes, delayed bone age, and osteopenia. Patients were assigned toeither the early or late treatment group, depending on whether or not dietary therapy was started before 3 monthsof age. Those in whom a blood phenylalanine level of under 10 mg/dl was maintained were assigned to the 'goodcontrol' group; others were classified as 'variable control'. The findings of radiographs of the left hand andlumbar BMD were evaluated in relation to the time of dietary therapy, and adequacy of treatment. RESULTS: Onlumbar BMD, four of 11 patients (36%) showed reduced bone density of more than 1 S.D. None of the 11 who underwentradiography of the left hand showed bony abnormalities such as spiculation or metaphyseal widening. In four of the11, bone age was less than chronological age by at least one year. According to Fisher's exact test there was norelation between delayed bone age , osteoporosis and the time and adequacy of dietary therapy (p >0.05). CONCLUSION: None of the 14 PKU patients who underwent dietary therapy had bony abnormalities such as spiculationor metaphyseal widening. In four of the 11, bone age was at least one year less than chronological age, and onlumbar BMD, osteoporosis was seen. For the evaluation of bone change in PKU patients, plain radiography and BMDare thus complementary.

The Difference in the Appearance of Proximal Humeral Epiphyseal Ossification Center on Chest Radiograph between the preterm and Full-term Infants

PURPOSE: To assess the difference in the appearance of the proximal humeral epiphyseal ossification center, as seen on chest radiograph, between preterm and full-term infants at the same corrected ages. MATERIALS AND METHODS: Forty two preterm infants born at 26-35 weeks of gestational age and 218 normal full-term infants born at 38-42 weeks were investigated. Because of various perinatal problems, the preterm infants were treated at a neonatal intensive care unit. Proximal humeral epiphyseal ossification centers were evaluated from chest radiographs, and in cases of preterm infants, the corected age of 0 month was defined as postconceptional 40 weeks. In preterm infants, the numbers of chest radiographs obtained were 42 at 0 month, 40 at 1 month, 37 at 2 months and 36 at 3 months of corrected age, while in those who were full-term, the numbers were 103 cases at 0 month, 42 at 1 month,42 at 2 months and 31 at 3 months of age. In the preterm group, alkaline phosphatase, calcium, phosphorus levels and simple wrist radiographs were checked. We then evaluated the difference of appearance of the proximal humeral epiphyseal ossification center between preterm and full-term infants at the same corrected ages, as well as the difference between causative diseases, between the normal and abnormal serologic group and between the normal and abnormal wrist group in preterm infants at the same corrected ages. Using Fisher's exact test, the data were analysed. RESULTS: The incidences of the proximal humeral epiphyseal ossification center in preterm infants were 2.4% (1/42) at 0 month, 20.0% (8/40) at 1 month, 43.2% (16/37) at 2 months and 69.4% (25/36) at 3 months; infull-term infants, the figures were 24.3% (25/103) at 0 month, 66.7% (28/42) at 1 month, 83.3% (35/42) at 2 months and 90.3% (28/31) at 3 months. At 0, 1, and 2 months, the incidences were thus seen to be lower in preterm than infull-term infants(p0.05). In preterm infants, there were no statistical differences between causative diseases, between the normal and abnormal serologic group and between the normal and abnormal wrist group(p>0.05). CONCLUSION: Up to the age of two months, the proximal humeral epiphyseal ossification center of preterm infants appears later than that of full-term infants at the same corrected age.

Standard Bone-Age of Infant and Children in Korea

To evaluate the developmental status of children and adolescents, bone-age chart based on the radiograph of hand and wrist has been used in many countries. The bone-age reflects not only the functional status of various hormones but also the influence of chronic disease, and it has been used more widely than other indices such as height-weight-age table. As the standard bone-age chart has not been established in Korea, the foreign bone-agechart has been used radiographs in the clinics. To make Korean standard bone-age chart, we took the radiographs ofthe left hand in about 5400 children covering the whole country, and 3407 radiographs of 1830 boys and 1577 girls ranging from two months to 16 years of age were selected and analyzed for bone maturity scores by TW2-20 method. The range of age were divided into 27 groups, and the radiographs of 50th percentile score were chosen as the standard bone-ages for the median age of each group. The youngest and oldest chronological age which had the same TW2-20 score of the standard bone-age were decided as the range of variation from the median age. we hope that Korean standard bone-age chart be used as the radiological criteria in the evaluation of the developmenta status in Korean children and adolescents.